Latest news with #ADCETRIS
National Post
03-06-2025
- Business
- National Post
European Commission Approves ADCETRIS® (brentuximab vedotin) for the Treatment of Adult Patients with Newly Diagnosed Stage IIb/III/IV Hodgkin Lymphoma in Combination with ECADD
Article content Article content – Second Approval in Frontline Hodgkin Lymphoma Broadens ADCETRIS' Therapeutic Reach, Adding to Six Previously Approved, Distinct Indications for ADCETRIS in the European Union Article content OSAKA, Japan & CAMBRIDGE, Mass. — Takeda (TSE:4502/NYSE:TAK) today announced that the European Commission (EC) approved ADCETRIS ® (brentuximab vedotin) in combination with etoposide, cyclophosphamide, doxorubicin, dacarbazine and dexamethasone (ECADD) – a chemotherapy regimen – in adult patients with newly diagnosed Stage IIb with risk factors/III/IV Hodgkin lymphoma. The decision follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) on April 25, 2025. Article content The approval for this ADCETRIS-based combination regimen, known as BrECADD, in frontline Hodgkin lymphoma is based on the results of the randomized Phase 3 HD21 trial. The study met its co-primary safety and efficacy endpoints, with BrECADD demonstrating significantly superior safety as assessed by treatment-related morbidity (TRMB) and non-inferior progression-free survival (PFS) in comparison to escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (eBEACOPP), a standard of care treatment in Europe 1. Article content 'Today's approval represents a significant advancement for patients with Hodgkin lymphoma in the European Union,' said Teresa Bitetti, president of the Global Oncology Business Unit at Takeda. 'This approval reinforces the role of ADCETRIS as a backbone in the treatment of specific lymphomas, offering healthcare professionals greater flexibility to tailor treatment plans according to individual patient needs. We're proud to contribute another impactful option for those diagnosed with this challenging disease.' Article content ADCETRIS is an antibody-drug conjugate (ADC) directed at CD30, a defining marker of Hodgkin lymphoma, and has been previously approved as a therapy for adult patients in the European Union (EU) in six distinct indications. This decision marks the second approval for an ADCETRIS-based combination regimen for frontline Hodgkin lymphoma, broadening the spectrum of available treatments for patients who historically have had limited options. Article content 'With BrECADD, patients now have a treatment option that not only offers greater curative potential 2* but also significantly reduces treatment-related morbidity compared to eBEACOPP,' said Peter Borchmann, MD, PhD, University Hospital of Cologne, Germany, and trial chairman of the HD21 study. 'This new ADCETRIS-based combination therapy may offer a new standard of care for frontline treatment of adults with advanced stage Hodgkin lymphoma, contributing to improved long-term outcomes for patients.' Article content About the HD21 Trial The HD21 study is a Phase 3, multi-country, prospective, open-label, randomized, multicenter trial conducted by the German Hodgkin Study Group (GHSG) with a PET-response adapted designed to assess the feasibility, efficacy, safety and tolerability of BrECADD, a novel, rationally designed, CD30-intensified frontline regimen for patients with advanced Hodgkin lymphoma. Article content Enrolled patients with newly diagnosed, Stage IIb with large mediastinal mass and/or extranodal lesions, Stage III or IV Hodgkin lymphoma were randomized to receive two cycles of either escalated BEACOPP or BrECADD, respectively, followed by interim PET staging. A decision is then made if patients received a further two or four cycles of escalated BEACOPP or BrECADD. Article content The HD21 trial aims to evaluate a new treatment regimen to minimize side effects, while maintaining similar responses to treatment. The study has co-primary endpoints: safety is assessed by treatment-related morbidity (TRMB) (superiority), a novel endpoint focused on clinically relevant, acute toxicities of primary chemotherapy, and efficacy is assessed by PFS (non-inferiority). Secondary endpoints are tumor response (complete response [CR] rate), overall survival (OS), infertility rate at one year, second malignancies, frequency of adverse events, therapy adherence and quality of life. Article content About ADCETRIS® (brentuximab vedotin) ADCETRIS is an antibody-drug conjugate (ADC) comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Pfizer's proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells. Article content ADCETRIS injection for intravenous infusion has received FDA approval for eight indications: Article content Adult patients with previously untreated Stage III/IV classical Hodgkin lymphoma (cHL) in combination with doxorubicin, vinblastine, and dacarbazine (2018) Pediatric patients 2 years and older with previously untreated high risk cHL in combination with doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide (2022) Adult patients with cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation (2015) Adult patients with cHL after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates (2011) Adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone (2018) Adult patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen (2011) Adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) after prior systemic therapy (2017) Adult patients with relapsed or refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma (HGBL), after two or more lines of systemic therapy who are not eligible for auto-HSCT or CAR T-cell therapy, in combination with lenalidomide and a rituximab product (2025) Article content Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-autologous stem cell transplantation (ASCT) consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression in 2017, adults with pcALCL or CD30-expressing MF who have had prior systemic therapy in 2018, for previously untreated Stage IV Hodgkin lymphoma in combination with doxorubicin, vinblastine, and dacarbazine in 2019, and for previously untreated adult patients with sALCL, peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) or angioimmunoblastic T-cell lymphoma (AITL), whose tumors express CD30, in combination with cyclophosphamide, doxorubicin, prednisone in 2019. Article content ADCETRIS received conditional marketing authorization from the European Commission in October 2012, and the specific obligations of the conditional marketing authorization were fulfilled in May 2022. The approved indications in the European Union are: (1) for the treatment of adult patients with previously untreated CD30-positive Stage III or IV Hodgkin lymphoma in combination with doxorubicin, vinblastine and dacarbazine (AVD), (2) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, (3) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (4) for the treatment of adult patients with relapsed or refractory sALCL, (5) for the treatment of adult patients with previously untreated sALCL in combination with CHP, (6) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy and (7) for the treatment of adult patients with previously untreated CD30+ Stage IIB with risk factors, Stage III or Stage IV HL in combination with etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone (BrECADD). Article content ADCETRIS has received marketing authorization by regulatory authorities in 80 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See Important Safety Information below. ADCETRIS is being evaluated broadly in more than 70 clinical trials, including a Phase 3 study in first-line Hodgkin lymphoma (ECHELON-1) and another Phase 3 study in first-line CD30-positive peripheral T-cell lymphomas (ECHELON-2), as well as trials in many additional types of CD30-positive malignancies. Article content Pfizer and Takeda fund joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs. Article content ADCETRIS (brentuximab vedotin) Important Safety Information (European Union) Please refer to Summary of Product Characteristics (SmPC) before prescribing. Article content Contraindications ADCETRIS is contraindicated for patients with hypersensitivity to brentuximab vedotin and its excipients. Combined use of bleomycin and ADCETRIS causes pulmonary toxicity. Article content Special Warnings and Precautions Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Article content Progressive multifocal leukoencephalopathy (PML): John Cunningham virus (JCV) reactivation resulting in PML and death can occur in ADCETRIS-treated patients. PML has been reported in patients who received this treatment after receiving multiple prior chemotherapy regimens. PML is a rare demyelinating disease of the central nervous system that results from reactivation of latent JCV and is often fatal. Article content Patients should be closely monitored for new or worsening neurological, cognitive, or behavioral signs or symptoms, which may be suggestive of PML. ADCETRIS should be held for any suspected case of PML. Suggested evaluation of PML includes neurology consultation, gadolinium-enhanced magnetic resonance imaging of the brain and cerebrospinal fluid analysis for JCV DNA by polymerase chain reaction or a brain biopsy with evidence of JCV. A negative JCV PCR does not exclude PML. Additional follow up and evaluation may be warranted if no alternative diagnosis can be established. ADCETRIS dosing should be permanently discontinued if a diagnosis of PML is confirmed. Article content The physician should be particularly alert to symptoms suggestive of PML that the patient may not notice (e.g., cognitive, neurological, or psychiatric symptoms). Article content Pancreatitis: Acute pancreatitis has been observed in patients treated with ADCETRIS. Fatal outcomes have been reported. Article content Patients should be closely monitored for new or worsening abdominal pain, which may be suggestive of acute pancreatitis. Patient evaluation may include physical examination, laboratory evaluation for serum amylase and serum lipase, and abdominal imaging, such as ultrasound and other appropriate diagnostic measures. ADCETRIS should be held for any suspected case of acute pancreatitis. ADCETRIS should be discontinued if a diagnosis of acute pancreatitis is confirmed. Article content Pulmonary Toxicity: Cases of pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome (ARDS), some with fatal outcomes, have been reported in patients receiving ADCETRIS. Although a causal association with ADCETRIS has not been established, the risk of pulmonary toxicity cannot be ruled out. In the event of new or worsening pulmonary symptoms (e.g. cough, dyspnoea), a prompt diagnostic evaluation should be performed and patients should be treated appropriately. Consider holding ADCETRIS dosing during evaluation and until symptomatic improvement. Article content Serious infections and opportunistic infections: Serious infections such as pneumonia, staphylococcal bacteremia, sepsis/septic shock (including fatal outcomes), and herpes zoster, cytomegalovirus (CMV) (reactivation) and opportunistic infections such as Pneumocystis jiroveci pneumonia and oral candidiasis have been reported in patients treated with ADCETRIS. Patients should be carefully monitored during treatment for the emergence of possible serious and opportunistic infections. Article content Infusion-related reactions (IRR): Immediate and delayed IRR, as well as anaphylaxis, have been reported with ADCETRIS. Article content Patients should be carefully monitored during and after infusion. If an anaphylactic reaction occurs, administration of ADCETRIS should be immediately and permanently discontinued and appropriate medical therapy should be administered. Article content If an IRR occurs, the infusion should be interrupted and appropriate medical management instituted. The infusion may be restarted at a slower rate after symptom resolution. Patients who have experienced a prior IRR should be premedicated for subsequent infusions. Premedication may include paracetamol, an antihistamine and a corticosteroid. Article content IRRs are more frequent and more severe in patients with antibodies to brentuximab vedotin. Article content Tumor lysis syndrome (TLS): TLS has been reported with ADCETRIS. Patients with rapidly proliferating tumour and high tumour burden are at risk of tumour lysis syndrome. These patients should be monitored closely and managed according to best medical practice. Management of TLS may include aggressive hydration, monitoring of renal function, correction of electrolyte abnormalities, anti-hyperuricaemic therapy, and supportive care. Article content Peripheral neuropathy (PN): ADCETRIS may cause peripheral neuropathy, both sensory and motor. ADCETRIS-induced peripheral neuropathy is typically an effect of cumulative exposure to this medicinal product and is reversible in most cases. In clinical trials, the majority of patients had resolution or improvement of their symptoms. Patients should be monitored for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paraesthesia, discomfort, a burning sensation, neuropathic pain or weakness. Patients experiencing new or worsening peripheral neuropathy may require a delay and a dose reduction of ADCETRIS or discontinuation of treatment. Article content Hematological toxicities: Grade 3 or Grade 4 anaemia, thrombocytopenia, and prolonged (≥ 1 week) Grade 3 or Grade 4 neutropenia can occur with ADCETRIS. Complete blood counts should be monitored prior to administration of each dose. Article content Febrile neutropenia: Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infection with an absolute neutrophil count < 1.0 x 10 9 /L, fever ≥ 38.5 0 C; ref CTCAE v3) has been reported with treatment with ADCETRIS. Complete blood counts should be monitored prior to administration of each dose of treatment. Patients should be monitored closely for fever and managed according to best medical practice if febrile neutropenia develops. Article content In combination therapy with AVD or CHP, advanced age was a risk factor for febrile neutropenia. When ADCETRIS is administered in combination with AVD or CHP, primary prophylaxis with G-CSF, beginning with the first dose, is recommended for all adult patients regardless of age. In combination therapy with AVD or CHP, advanced age was a risk factor for febrile neutropenia. Article content Severe cutaneous adverse reactions (SCARs): Cases of SCARs, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with ADCETRIS. Fatal outcomes have been reported for SJS and TEN. If SJS, TEN or DRESS occur, ADCETRIS should be discontinued, and appropriate medical therapy should be administered. Article content Gastrointestinal (GI) Complications: GI complications including intestinal obstruction, ileus, enterocolitis, neutropenic colitis, erosion, ulcer, perforation and haemorrhage, some with fatal outcomes, have been reported in patients treated with ADCETRIS. In the event of new or worsening GI symptoms, perform a prompt diagnostic evaluation and treat appropriately. Article content Hepatotoxicity: Hepatotoxicity in the form of elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) has been reported with ADCETRIS. Serious cases of hepatotoxicity, including fatal outcomes, have also occurred. Pre-existing liver disease, comorbidities, and concomitant medications may also increase the risk. Liver function should be tested before initiating the treatment and routinely monitored in patients receiving ADCETRIS. Patients experiencing hepatotoxicity may require a delay, change in dose or discontinuation of ADCETRIS. Article content Hyperglycemia: Hyperglycaemia has been reported during clinical trials in patients with an elevated Body Mass Index (BMI) with or without a history of diabetes mellitus. However, any patient who experiences an event of hyperglycaemia should have their serum glucose closely monitored. Anti-diabetic treatment should be administered as appropriate. Article content Infusion site extravasation: Extravasation during intravenous infusion has occurred. Given the possibility of extravasation, it is recommended to closely monitor the infusion site for possible infiltration during drug administration. Article content Renal and Hepatic Impairment: There is limited experience in patients with renal and hepatic impairment. Available data indicate that MMAE clearance might be affected by severe renal impairment, hepatic impairment, and by low serum albumin concentrations. Article content CD30+ CTCL: The size of the treatment effect in CD30 + CTCL subtypes other than mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL) is not clear due to lack of high level evidence. In two single arm phase II studies of ADCETRIS, disease activity has been shown in the subtypes Sézary syndrome (SS), lymphomatoid papulosis (LyP) and mixed CTCL histology. These data suggest that efficacy and safety can be extrapolated to other CTCL CD30+ subtypes. Nevertheless, ADCETRIS should be used with caution in other CD30+ CTCL patients after careful consideration of the potential benefit-risk on an individual basis. Article content Sodium content in excipients: This medicinal product contains 13.2 mg sodium per vial, equivalent to 0.7% of the WHO recommended maximum daily intake of 2 g sodium for an adult. Article content Polysorbate content in excipients: This medicinal product contains 2 mg of polysorbate 80 per vial, equivalent to 0.2 mg/ml. Polysorbates may cause allergic reactions. Article content Interactions Interaction with medicinal products metabolised through CYP3A4 route (CYP3A4 inhibitors/inducers) Co‑administration of brentuximab vedotin with ketoconazole, a strong CYP3A4 and P‑gp inhibitor, increased the exposure to the antimicrotubule agent MMAE by approximately 73%, and did not alter the plasma exposure to brentuximab vedotin. Therefore, co‑administration of brentuximab vedotin with strong CYP3A4 and P‑gp inhibitors may increase the incidence of neutropenia. If neutropenia develops, refer to Tables 1 and 2 for dosing recommendations for neutropenia. Article content Co‑administration of brentuximab vedotin with rifampicin, a strong CYP3A4 inducer, did not alter the plasma exposure to brentuximab vedotin. Though PK data are limited, co‑administration of rifampicin appeared to reduce plasma concentrations of MMAE metabolites that could be assayed. Article content Co‑administration of midazolam, a CYP3A4 substrate, with brentuximab vedotin did not alter the metabolism of midazolam; therefore brentuximab vedotin is not expected to alter the exposure to medicines that are metabolized by CYP3A4 enzymes. Article content Etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone (BrECADD regimen) The pharmacokinetics of ADC and MMAE have not been characterized in the setting of BrECADD. Exposures of brentuximab vedotin and concurrent chemotherapy are not expected to be affected in the BrECADD regimen. Article content Fertility, pregnancy and lactation Women of childbearing potential: Women of childbearing potential should be using two methods of effective contraception during treatment with ADCETRIS and until 6 months after treatment. Article content Pregnancy: There are no data from the use of ADCETRIS in pregnant women. Studies in animals have shown reproductive toxicity. ADCETRIS should not be used during pregnancy unless the benefit to the mother outweighs the potential risks to the fetus. If a pregnant woman needs to be treated she should be clearly advised on the potential risk to the fetus. Article content Breast-feeding: There is no data as to whether brentuximab vedotin or its metabolites are excreted in human milk. A risk to the newborn/infant cannot be excluded. A decision should be made whether to discontinue breast-feeding or to discontinue/abstain from this therapy, taking into account a potential risk of breast-feeding for the child and the benefit of therapy for the woman. Article content Fertility: In non-clinical studies, brentuximab vedotin treatment has resulted in testicular toxicity, and may alter male fertility. MMAE has been shown to have anagenic properties. Therefore, men being treated with this medicine are advised to have sperm samples frozen and stored before treatment. Men being treated with this medicine are advised not to father a child during treatment and for up to 6 months following the last dose. Article content Effects on ability to drive and use machines: ADCETRIS may have a moderate influence on the ability to drive and use machines (e.g. dizziness). Article content Undesirable Effects Monotherapy: The most frequent adverse reactions (≥10%) were infections, peripheral sensory neuropathy, nausea, fatigue, diarrhea, pyrexia, upper respiratory tract infection, neutropenia, rash, cough, vomiting, arthralgia, peripheral motor neuropathy, infusion-related reactions, pruritus, constipation, dyspnea, weight decreased, myalgia and abdominal pain. Serious adverse drug reactions occurred in 12% of patients. The frequency of unique serious adverse drug reactions was ≤1%. Adverse events led to treatment discontinuation in 24% of patients. Article content Combination Therapy: In the studies of ADCETRIS as combination therapy in 662 patients with previously untreated advanced HL and 223 patients with previously untreated CD30+ PTCL, the most common adverse reactions (≥ 10%) were: infections, neutropenia, peripheral sensory neuropathy, nausea, constipation, vomiting, diarrhea, fatigue, pyrexia, alopecia, anemia, weight decreased, stomatitis, febrile neutropenia, abdominal pain, decreased appetite, insomnia, bone pain, rash, cough, dyspnea, arthralgia, myalgia, back pain, peripheral motor neuropathy, upper respiratory tract infection, and dizziness. In patients receiving ADCETRIS combination therapy, serious adverse reactions occurred in 34% of patients. Serious adverse reactions occurring in ≥ 3% of patients included febrile neutropenia (15%), pyrexia (5%), and neutropenia (3%). Adverse events led to treatment discontinuation in 10% of patients. Article content In patients receiving ADCETRIS combination therapy, serious adverse reactions occurred in 34% of patients. Serious adverse reactions occurring in ≥ 3% of patients included febrile neutropenia (15%), pyrexia (5%), and neutropenia (3%). Adverse events led to treatment discontinuation in 10% of patients. Article content Adverse events led to treatment discontinuation in 10% of patients. Adverse events that led to treatment discontinuation in ≥ 2% of patients included peripheral sensory neuropathy, and peripheral neuropathy. Article content Combination Therapy (BrECADD regimen): In the HD21 study, 747 patients received BrECADD, and 741 patients received eBEACOPP. The safety profile of ADCETRIS in patients receiving BrECADD remained consistent with other combination therapy (AVD/CHP). Article content Serious adverse reactions occurred in 39.4% patients receiving BrECADD treatment, and 36.4% in patients who received eBEACOPP. The most common serious adverse reactions in patients who received BrECADD (> 3%) were febrile neutropenia (19.3%), pyrexia (3.9%), and neutropenia (3.2%). Article content Serious cardiac adverse reactions occurred in 2.7% of patients receiving BrECADD and 1.1% of patients receiving eBEACOPP. The most common serious cardiac adverse reaction in patients who received BrECADD (>0.5%) was tachycardia (0.9%). Article content Serious adverse events led to treatment discontinuation in 2% of patients in both BrECADD and eBEACOPP arms. The most common serious adverse events that led to discontinuation in the BrECADD arm were febrile neutropenia (0.3%) and cardiac failure (0.3%). Article content CONTRAINDICATION Contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation). Article content Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening PN may require a delay, change in dose, or discontinuation of ADCETRIS. Article content Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid. Article content Hematologic toxicities: Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS. Article content Administer G-CSF primary prophylaxis beginning with Cycle 1 for adult patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL, and pediatric patients who receive ADCETRIS in combination with chemotherapy for previously untreated high risk cHL. Article content Monitor complete blood counts prior to each ADCETRIS dose. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses. Article content Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for infections. Article content Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden may be at increased risk. Monitor closely and take appropriate measures. Article content Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment. Avoid use in patients with severe renal impairment. Article content Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment. Avoid use in patients with moderate or severe hepatic impairment. Article content Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS. Article content PML: Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed. Article content Pulmonary toxicity: Fatal and serious events of noninfectious pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, have been reported. Monitor patients for signs and symptoms, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement. Article content Serious dermatologic reactions: Fatal and serious cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy. Article content Gastrointestinal (GI) complications: Fatal and serious cases of acute pancreatitis have been reported. Other fatal and serious GI complications include perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. Lymphoma with pre-existing GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, including severe abdominal pain, perform a prompt diagnostic evaluation and treat appropriately. Article content Hyperglycemia: Serious cases, such as new-onset hyperglycemia, exacerbation of pre-existing diabetes mellitus, and ketoacidosis (including fatal outcomes) have been reported with ADCETRIS. Hyperglycemia occurred more frequently in patients with high body mass index or diabetes. Monitor serum glucose and if hyperglycemia develops, administer anti-hyperglycemic medications as clinically indicated. Article content Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of this potential risk, and to use effective contraception during ADCETRIS treatment and for 2 months after the last dose of ADCETRIS. Advise male patients with female partners of reproductive potential to use effective contraception during ADCETRIS treatment and for 4 months after the last dose of ADCETRIS. Article content ADVERSE REACTIONS The most common adverse reactions (≥20%) in adult patients are peripheral neuropathy, nausea, fatigue, musculoskeletal pain, constipation, diarrhea, vomiting, pyrexia, upper respiratory tract infection, mucositis, abdominal pain, and rash. The most common laboratory abnormalities (≥20%) in adult patients are decreased neutrophils, increased creatinine, decreased hemoglobin, decreased lymphocytes, increased glucose, increased ALT, and increased AST. Article content The most common Grade ≥3 adverse reactions (≥5%) in combination with AVEPC in pediatric patients were neutropenia, anemia, thrombocytopenia, febrile neutropenia, stomatitis, and infection. Article content DRUG INTERACTIONS Concomitant use of strong CYP3A4 inhibitors has the potential to affect the exposure to monomethyl auristatin E (MMAE). Closely monitor adverse reactions. Article content Please see the full Prescribing Information, including BOXED WARNING, for ADCETRIS here. Article content About Takeda Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit Article content Important Notice For the purposes of this notice, 'press release' means this document, any oral presentation, any question and answer session and any written or oral material discussed or distributed by Takeda Pharmaceutical Company Limited ('Takeda') regarding this release. 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Past performance is not an indicator of future results and the results or statements of Takeda in this press release may not be indicative of, and are not an estimate, forecast, guarantee or projection of Takeda's future results. Article content Medical Information This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development. Article content Footnotes: Article content *While late relapse is rare, PFS status after 5 years does not guarantee cure. Patients should be monitored and encouraged to report any return of symptoms as appropriate. Article content References: Article content Borchmann P, Ferdinandus J, Schneider G, et al. Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial [published correction appears in Lancet. 2024 Nov 30;404(10468):2164. doi: 10.1016/S0140-6736(24)02571-6.]. Lancet. 2024;404(10450):341-352. Bröckelmann PJ, Goergen H, Kohnhorst C, von Tresckow B, Moccia A, Markova J, Meissner J, Kerkhoff A, Ludwig WD, Fuchs M, Borchmann P, Engert A. Late Relapse of Classical Hodgkin Lymphoma: An Analysis of the German Hodgkin Study Group HD7 to HD12 Trials. J Clin Oncol. 2017 May 1;35(13):1444-1450. doi: 10.1200/JCO.2016.71.3289. Epub 2017 Feb 27. PMID: 28240973. Article content Article content Article content Article content Article content Contacts Article content Takeda Media Contacts: Japanese Media Tsuyoshi Tada Article content Article content
Business Wire
03-06-2025
- Business
- Business Wire
European Commission Approves ADCETRIS ® (brentuximab vedotin) for the Treatment of Adult Patients with Newly Diagnosed Stage IIb/III/IV Hodgkin Lymphoma in Combination with ECADD
OSAKA, Japan & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Takeda (TSE:4502/NYSE:TAK) today announced that the European Commission (EC) approved ADCETRIS ® (brentuximab vedotin) in combination with etoposide, cyclophosphamide, doxorubicin, dacarbazine and dexamethasone (ECADD) – a chemotherapy regimen – in adult patients with newly diagnosed Stage IIb with risk factors/III/IV Hodgkin lymphoma. The decision follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) on April 25, 2025. The approval for this ADCETRIS-based combination regimen, known as BrECADD, in frontline Hodgkin lymphoma is based on the results of the randomized Phase 3 HD21 trial. The study met its co-primary safety and efficacy endpoints, with BrECADD demonstrating significantly superior safety as assessed by treatment-related morbidity (TRMB) and non-inferior progression-free survival (PFS) in comparison to escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (eBEACOPP), a standard of care treatment in Europe 1. 'Today's approval represents a significant advancement for patients with Hodgkin lymphoma in the European Union,' said Teresa Bitetti, president of the Global Oncology Business Unit at Takeda. "This approval reinforces the role of ADCETRIS as a backbone in the treatment of specific lymphomas, offering healthcare professionals greater flexibility to tailor treatment plans according to individual patient needs. We're proud to contribute another impactful option for those diagnosed with this challenging disease.' ADCETRIS is an antibody-drug conjugate (ADC) directed at CD30, a defining marker of Hodgkin lymphoma, and has been previously approved as a therapy for adult patients in the European Union (EU) in six distinct indications. This decision marks the second approval for an ADCETRIS-based combination regimen for frontline Hodgkin lymphoma, broadening the spectrum of available treatments for patients who historically have had limited options. 'With BrECADD, patients now have a treatment option that not only offers greater curative potential 2* but also significantly reduces treatment-related morbidity compared to eBEACOPP,' said Peter Borchmann, MD, PhD, University Hospital of Cologne, Germany, and trial chairman of the HD21 study. 'This new ADCETRIS-based combination therapy may offer a new standard of care for frontline treatment of adults with advanced stage Hodgkin lymphoma, contributing to improved long-term outcomes for patients.' About the HD21 Trial The HD21 study is a Phase 3, multi-country, prospective, open-label, randomized, multicenter trial conducted by the German Hodgkin Study Group (GHSG) with a PET-response adapted designed to assess the feasibility, efficacy, safety and tolerability of BrECADD, a novel, rationally designed, CD30-intensified frontline regimen for patients with advanced Hodgkin lymphoma. Enrolled patients with newly diagnosed, Stage IIb with large mediastinal mass and/or extranodal lesions, Stage III or IV Hodgkin lymphoma were randomized to receive two cycles of either escalated BEACOPP or BrECADD, respectively, followed by interim PET staging. A decision is then made if patients received a further two or four cycles of escalated BEACOPP or BrECADD. The HD21 trial aims to evaluate a new treatment regimen to minimize side effects, while maintaining similar responses to treatment. The study has co-primary endpoints: safety is assessed by treatment-related morbidity (TRMB) (superiority), a novel endpoint focused on clinically relevant, acute toxicities of primary chemotherapy, and efficacy is assessed by PFS (non-inferiority). Secondary endpoints are tumor response (complete response [CR] rate), overall survival (OS), infertility rate at one year, second malignancies, frequency of adverse events, therapy adherence and quality of life. About ADCETRIS® (brentuximab vedotin) ADCETRIS is an antibody-drug conjugate (ADC) comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Pfizer's proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells. ADCETRIS injection for intravenous infusion has received FDA approval for eight indications: Adult patients with previously untreated Stage III/IV classical Hodgkin lymphoma (cHL) in combination with doxorubicin, vinblastine, and dacarbazine (2018) Pediatric patients 2 years and older with previously untreated high risk cHL in combination with doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide (2022) Adult patients with cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation (2015) Adult patients with cHL after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates (2011) Adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone (2018) Adult patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen (2011) Adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) after prior systemic therapy (2017) Adult patients with relapsed or refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma (HGBL), after two or more lines of systemic therapy who are not eligible for auto-HSCT or CAR T-cell therapy, in combination with lenalidomide and a rituximab product (2025) Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-autologous stem cell transplantation (ASCT) consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression in 2017, adults with pcALCL or CD30-expressing MF who have had prior systemic therapy in 2018, for previously untreated Stage IV Hodgkin lymphoma in combination with doxorubicin, vinblastine, and dacarbazine in 2019, and for previously untreated adult patients with sALCL, peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) or angioimmunoblastic T-cell lymphoma (AITL), whose tumors express CD30, in combination with cyclophosphamide, doxorubicin, prednisone in 2019. ADCETRIS received conditional marketing authorization from the European Commission in October 2012, and the specific obligations of the conditional marketing authorization were fulfilled in May 2022. The approved indications in the European Union are: (1) for the treatment of adult patients with previously untreated CD30-positive Stage III or IV Hodgkin lymphoma in combination with doxorubicin, vinblastine and dacarbazine (AVD), (2) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, (3) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (4) for the treatment of adult patients with relapsed or refractory sALCL, (5) for the treatment of adult patients with previously untreated sALCL in combination with CHP, (6) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy and (7) for the treatment of adult patients with previously untreated CD30+ Stage IIB with risk factors, Stage III or Stage IV HL in combination with etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone (BrECADD). ADCETRIS has received marketing authorization by regulatory authorities in 80 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See Important Safety Information below. ADCETRIS is being evaluated broadly in more than 70 clinical trials, including a Phase 3 study in first-line Hodgkin lymphoma (ECHELON-1) and another Phase 3 study in first-line CD30-positive peripheral T-cell lymphomas (ECHELON-2), as well as trials in many additional types of CD30-positive malignancies. Pfizer and Takeda fund joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs. ADCETRIS (brentuximab vedotin) Important Safety Information (European Union) Please refer to Summary of Product Characteristics (SmPC) before prescribing. Contraindications ADCETRIS is contraindicated for patients with hypersensitivity to brentuximab vedotin and its excipients. Combined use of bleomycin and ADCETRIS causes pulmonary toxicity. Special Warnings and Precautions Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Progressive multifocal leukoencephalopathy (PML): John Cunningham virus (JCV) reactivation resulting in PML and death can occur in ADCETRIS-treated patients. PML has been reported in patients who received this treatment after receiving multiple prior chemotherapy regimens. PML is a rare demyelinating disease of the central nervous system that results from reactivation of latent JCV and is often fatal. Patients should be closely monitored for new or worsening neurological, cognitive, or behavioral signs or symptoms, which may be suggestive of PML. ADCETRIS should be held for any suspected case of PML. Suggested evaluation of PML includes neurology consultation, gadolinium-enhanced magnetic resonance imaging of the brain and cerebrospinal fluid analysis for JCV DNA by polymerase chain reaction or a brain biopsy with evidence of JCV. A negative JCV PCR does not exclude PML. Additional follow up and evaluation may be warranted if no alternative diagnosis can be established. ADCETRIS dosing should be permanently discontinued if a diagnosis of PML is confirmed. The physician should be particularly alert to symptoms suggestive of PML that the patient may not notice (e.g., cognitive, neurological, or psychiatric symptoms). Pancreatitis: Acute pancreatitis has been observed in patients treated with ADCETRIS. Fatal outcomes have been reported. Patients should be closely monitored for new or worsening abdominal pain, which may be suggestive of acute pancreatitis. Patient evaluation may include physical examination, laboratory evaluation for serum amylase and serum lipase, and abdominal imaging, such as ultrasound and other appropriate diagnostic measures. ADCETRIS should be held for any suspected case of acute pancreatitis. ADCETRIS should be discontinued if a diagnosis of acute pancreatitis is confirmed. Pulmonary Toxicity: Cases of pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome (ARDS), some with fatal outcomes, have been reported in patients receiving ADCETRIS. Although a causal association with ADCETRIS has not been established, the risk of pulmonary toxicity cannot be ruled out. In the event of new or worsening pulmonary symptoms (e.g. cough, dyspnoea), a prompt diagnostic evaluation should be performed and patients should be treated appropriately. Consider holding ADCETRIS dosing during evaluation and until symptomatic improvement. Serious infections and opportunistic infections: Serious infections such as pneumonia, staphylococcal bacteremia, sepsis/septic shock (including fatal outcomes), and herpes zoster, cytomegalovirus (CMV) (reactivation) and opportunistic infections such as Pneumocystis jiroveci pneumonia and oral candidiasis have been reported in patients treated with ADCETRIS. Patients should be carefully monitored during treatment for the emergence of possible serious and opportunistic infections. Infusion-related reactions (IRR): Immediate and delayed IRR, as well as anaphylaxis, have been reported with ADCETRIS. Patients should be carefully monitored during and after infusion. If an anaphylactic reaction occurs, administration of ADCETRIS should be immediately and permanently discontinued and appropriate medical therapy should be administered. If an IRR occurs, the infusion should be interrupted and appropriate medical management instituted. The infusion may be restarted at a slower rate after symptom resolution. Patients who have experienced a prior IRR should be premedicated for subsequent infusions. Premedication may include paracetamol, an antihistamine and a corticosteroid. IRRs are more frequent and more severe in patients with antibodies to brentuximab vedotin. Tumor lysis syndrome (TLS): TLS has been reported with ADCETRIS. Patients with rapidly proliferating tumour and high tumour burden are at risk of tumour lysis syndrome. These patients should be monitored closely and managed according to best medical practice. Management of TLS may include aggressive hydration, monitoring of renal function, correction of electrolyte abnormalities, anti-hyperuricaemic therapy, and supportive care. Peripheral neuropathy (PN): ADCETRIS may cause peripheral neuropathy, both sensory and motor. ADCETRIS-induced peripheral neuropathy is typically an effect of cumulative exposure to this medicinal product and is reversible in most cases. In clinical trials, the majority of patients had resolution or improvement of their symptoms. Patients should be monitored for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paraesthesia, discomfort, a burning sensation, neuropathic pain or weakness. Patients experiencing new or worsening peripheral neuropathy may require a delay and a dose reduction of ADCETRIS or discontinuation of treatment. Hematological toxicities: Grade 3 or Grade 4 anaemia, thrombocytopenia, and prolonged (≥ 1 week) Grade 3 or Grade 4 neutropenia can occur with ADCETRIS. Complete blood counts should be monitored prior to administration of each dose. Febrile neutropenia: Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infection with an absolute neutrophil count < 1.0 x 10 9 /L, fever ≥ 38.5 0 C; ref CTCAE v3) has been reported with treatment with ADCETRIS. Complete blood counts should be monitored prior to administration of each dose of treatment. Patients should be monitored closely for fever and managed according to best medical practice if febrile neutropenia develops. In combination therapy with AVD or CHP, advanced age was a risk factor for febrile neutropenia. When ADCETRIS is administered in combination with AVD or CHP, primary prophylaxis with G-CSF, beginning with the first dose, is recommended for all adult patients regardless of age. In combination therapy with AVD or CHP, advanced age was a risk factor for febrile neutropenia. Severe cutaneous adverse reactions (SCARs): Cases of SCARs, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with ADCETRIS. Fatal outcomes have been reported for SJS and TEN. If SJS, TEN or DRESS occur, ADCETRIS should be discontinued, and appropriate medical therapy should be administered. Gastrointestinal (GI) Complications: GI complications including intestinal obstruction, ileus, enterocolitis, neutropenic colitis, erosion, ulcer, perforation and haemorrhage, some with fatal outcomes, have been reported in patients treated with ADCETRIS. In the event of new or worsening GI symptoms, perform a prompt diagnostic evaluation and treat appropriately. Hepatotoxicity: Hepatotoxicity in the form of elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) has been reported with ADCETRIS. Serious cases of hepatotoxicity, including fatal outcomes, have also occurred. Pre-existing liver disease, comorbidities, and concomitant medications may also increase the risk. Liver function should be tested before initiating the treatment and routinely monitored in patients receiving ADCETRIS. Patients experiencing hepatotoxicity may require a delay, change in dose or discontinuation of ADCETRIS. Hyperglycemia: Hyperglycaemia has been reported during clinical trials in patients with an elevated Body Mass Index (BMI) with or without a history of diabetes mellitus. However, any patient who experiences an event of hyperglycaemia should have their serum glucose closely monitored. Anti-diabetic treatment should be administered as appropriate. Infusion site extravasation: Extravasation during intravenous infusion has occurred. Given the possibility of extravasation, it is recommended to closely monitor the infusion site for possible infiltration during drug administration. Renal and Hepatic Impairment: There is limited experience in patients with renal and hepatic impairment. Available data indicate that MMAE clearance might be affected by severe renal impairment, hepatic impairment, and by low serum albumin concentrations. CD30+ CTCL: The size of the treatment effect in CD30 + CTCL subtypes other than mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL) is not clear due to lack of high level evidence. In two single arm phase II studies of ADCETRIS, disease activity has been shown in the subtypes Sézary syndrome (SS), lymphomatoid papulosis (LyP) and mixed CTCL histology. These data suggest that efficacy and safety can be extrapolated to other CTCL CD30+ subtypes. Nevertheless, ADCETRIS should be used with caution in other CD30+ CTCL patients after careful consideration of the potential benefit-risk on an individual basis. Sodium content in excipients: This medicinal product contains 13.2 mg sodium per vial, equivalent to 0.7% of the WHO recommended maximum daily intake of 2 g sodium for an adult. Polysorbate content in excipients: This medicinal product contains 2 mg of polysorbate 80 per vial, equivalent to 0.2 mg/ml. Polysorbates may cause allergic reactions. Interactions Interaction with medicinal products metabolised through CYP3A4 route (CYP3A4 inhibitors/inducers) Co‑administration of brentuximab vedotin with ketoconazole, a strong CYP3A4 and P‑gp inhibitor, increased the exposure to the antimicrotubule agent MMAE by approximately 73%, and did not alter the plasma exposure to brentuximab vedotin. Therefore, co‑administration of brentuximab vedotin with strong CYP3A4 and P‑gp inhibitors may increase the incidence of neutropenia. If neutropenia develops, refer to Tables 1 and 2 for dosing recommendations for neutropenia. Co‑administration of brentuximab vedotin with rifampicin, a strong CYP3A4 inducer, did not alter the plasma exposure to brentuximab vedotin. Though PK data are limited, co‑administration of rifampicin appeared to reduce plasma concentrations of MMAE metabolites that could be assayed. Co‑administration of midazolam, a CYP3A4 substrate, with brentuximab vedotin did not alter the metabolism of midazolam; therefore brentuximab vedotin is not expected to alter the exposure to medicines that are metabolized by CYP3A4 enzymes. Etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone (BrECADD regimen) The pharmacokinetics of ADC and MMAE have not been characterized in the setting of BrECADD. Exposures of brentuximab vedotin and concurrent chemotherapy are not expected to be affected in the BrECADD regimen. Fertility, pregnancy and lactation Women of childbearing potential: Women of childbearing potential should be using two methods of effective contraception during treatment with ADCETRIS and until 6 months after treatment. Pregnancy: There are no data from the use of ADCETRIS in pregnant women. Studies in animals have shown reproductive toxicity. ADCETRIS should not be used during pregnancy unless the benefit to the mother outweighs the potential risks to the fetus. If a pregnant woman needs to be treated she should be clearly advised on the potential risk to the fetus. Breast-feeding: There is no data as to whether brentuximab vedotin or its metabolites are excreted in human milk. A risk to the newborn/infant cannot be excluded. A decision should be made whether to discontinue breast-feeding or to discontinue/abstain from this therapy, taking into account a potential risk of breast-feeding for the child and the benefit of therapy for the woman. Fertility: In non-clinical studies, brentuximab vedotin treatment has resulted in testicular toxicity, and may alter male fertility. MMAE has been shown to have anagenic properties. Therefore, men being treated with this medicine are advised to have sperm samples frozen and stored before treatment. Men being treated with this medicine are advised not to father a child during treatment and for up to 6 months following the last dose. Effects on ability to drive and use machines: ADCETRIS may have a moderate influence on the ability to drive and use machines (e.g. dizziness). Undesirable Effects Monotherapy: The most frequent adverse reactions (≥10%) were infections, peripheral sensory neuropathy, nausea, fatigue, diarrhea, pyrexia, upper respiratory tract infection, neutropenia, rash, cough, vomiting, arthralgia, peripheral motor neuropathy, infusion-related reactions, pruritus, constipation, dyspnea, weight decreased, myalgia and abdominal pain. Serious adverse drug reactions occurred in 12% of patients. The frequency of unique serious adverse drug reactions was ≤1%. Adverse events led to treatment discontinuation in 24% of patients. Combination Therapy: In the studies of ADCETRIS as combination therapy in 662 patients with previously untreated advanced HL and 223 patients with previously untreated CD30+ PTCL, the most common adverse reactions (≥ 10%) were: infections, neutropenia, peripheral sensory neuropathy, nausea, constipation, vomiting, diarrhea, fatigue, pyrexia, alopecia, anemia, weight decreased, stomatitis, febrile neutropenia, abdominal pain, decreased appetite, insomnia, bone pain, rash, cough, dyspnea, arthralgia, myalgia, back pain, peripheral motor neuropathy, upper respiratory tract infection, and dizziness. In patients receiving ADCETRIS combination therapy, serious adverse reactions occurred in 34% of patients. Serious adverse reactions occurring in ≥ 3% of patients included febrile neutropenia (15%), pyrexia (5%), and neutropenia (3%). Adverse events led to treatment discontinuation in 10% of patients. In patients receiving ADCETRIS combination therapy, serious adverse reactions occurred in 34% of patients. Serious adverse reactions occurring in ≥ 3% of patients included febrile neutropenia (15%), pyrexia (5%), and neutropenia (3%). Adverse events led to treatment discontinuation in 10% of patients. Adverse events led to treatment discontinuation in 10% of patients. Adverse events that led to treatment discontinuation in ≥ 2% of patients included peripheral sensory neuropathy, and peripheral neuropathy. Combination Therapy (BrECADD regimen): In the HD21 study, 747 patients received BrECADD, and 741 patients received eBEACOPP. The safety profile of ADCETRIS in patients receiving BrECADD remained consistent with other combination therapy (AVD/CHP). Serious adverse reactions occurred in 39.4% patients receiving BrECADD treatment, and 36.4% in patients who received eBEACOPP. The most common serious adverse reactions in patients who received BrECADD (> 3%) were febrile neutropenia (19.3%), pyrexia (3.9%), and neutropenia (3.2%). Serious cardiac adverse reactions occurred in 2.7% of patients receiving BrECADD and 1.1% of patients receiving eBEACOPP. The most common serious cardiac adverse reaction in patients who received BrECADD (>0.5%) was tachycardia (0.9%). Serious adverse events led to treatment discontinuation in 2% of patients in both BrECADD and eBEACOPP arms. The most common serious adverse events that led to discontinuation in the BrECADD arm were febrile neutropenia (0.3%) and cardiac failure (0.3%). ADCETRIS ® (brentuximab vedotin) for injection U.S. Important Safety Information BOXED WARNING PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML, and death can occur in ADCETRIS-treated patients. CONTRAINDICATION Contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation). WARNINGS AND PRECAUTIONS Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening PN may require a delay, change in dose, or discontinuation of ADCETRIS. Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid. Hematologic toxicities: Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS. Administer G-CSF primary prophylaxis beginning with Cycle 1 for adult patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL, and pediatric patients who receive ADCETRIS in combination with chemotherapy for previously untreated high risk cHL. Monitor complete blood counts prior to each ADCETRIS dose. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses. Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for infections. Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden may be at increased risk. Monitor closely and take appropriate measures. Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment. Avoid use in patients with severe renal impairment. Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment. Avoid use in patients with moderate or severe hepatic impairment. Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS. PML: Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed. Pulmonary toxicity: Fatal and serious events of noninfectious pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, have been reported. Monitor patients for signs and symptoms, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement. Serious dermatologic reactions: Fatal and serious cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy. Gastrointestinal (GI) complications: Fatal and serious cases of acute pancreatitis have been reported. Other fatal and serious GI complications include perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. Lymphoma with pre-existing GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, including severe abdominal pain, perform a prompt diagnostic evaluation and treat appropriately. Hyperglycemia: Serious cases, such as new-onset hyperglycemia, exacerbation of pre-existing diabetes mellitus, and ketoacidosis (including fatal outcomes) have been reported with ADCETRIS. Hyperglycemia occurred more frequently in patients with high body mass index or diabetes. Monitor serum glucose and if hyperglycemia develops, administer anti-hyperglycemic medications as clinically indicated. Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of this potential risk, and to use effective contraception during ADCETRIS treatment and for 2 months after the last dose of ADCETRIS. Advise male patients with female partners of reproductive potential to use effective contraception during ADCETRIS treatment and for 4 months after the last dose of ADCETRIS. ADVERSE REACTIONS The most common adverse reactions (≥20%) in adult patients are peripheral neuropathy, nausea, fatigue, musculoskeletal pain, constipation, diarrhea, vomiting, pyrexia, upper respiratory tract infection, mucositis, abdominal pain, and rash. The most common laboratory abnormalities (≥20%) in adult patients are decreased neutrophils, increased creatinine, decreased hemoglobin, decreased lymphocytes, increased glucose, increased ALT, and increased AST. The most common Grade ≥3 adverse reactions (≥5%) in combination with AVEPC in pediatric patients were neutropenia, anemia, thrombocytopenia, febrile neutropenia, stomatitis, and infection. DRUG INTERACTIONS Concomitant use of strong CYP3A4 inhibitors has the potential to affect the exposure to monomethyl auristatin E (MMAE). Closely monitor adverse reactions. USE IN SPECIAL POPULATIONS Lactation: Breastfeeding is not recommended during ADCETRIS treatment. Please see the full Prescribing Information, including BOXED WARNING, for ADCETRIS here. About Takeda Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. 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Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial [published correction appears in Lancet. 2024 Nov 30;404(10468):2164. doi: 10.1016/S0140-6736(24)02571-6.]. Lancet. 2024;404(10450):341-352. Bröckelmann PJ, Goergen H, Kohnhorst C, von Tresckow B, Moccia A, Markova J, Meissner J, Kerkhoff A, Ludwig WD, Fuchs M, Borchmann P, Engert A. Late Relapse of Classical Hodgkin Lymphoma: An Analysis of the German Hodgkin Study Group HD7 to HD12 Trials. J Clin Oncol. 2017 May 1;35(13):1444-1450. doi: 10.1200/JCO.2016.71.3289. Epub 2017 Feb 27. PMID: 28240973.
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U.S. FDA Approves Pfizer's ADCETRIS® Combination Regimen for the treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Approval is based on positive data from the Phase 3 ECHELON-3 trial, which demonstrated ADCETRIS regimen reduced the risk of death by 37%, a statistically significant, clinically meaningful improvement in overall survival (OS), compared to lenalidomide and rituximab plus placebo ECHELON-3 is the first Phase 3 trial to demonstrate OS advantage over lenalidomide and rituximab plus placebo for patients with at least 2 prior lines of therapy with R/R diffuse large B-cell lymphoma (DLBCL) Milestone represents the eighth FDA-approved indication for ADCETRIS, reinforcing its use as a standard of care for certain lymphomas NEW YORK, February 12, 2025--(BUSINESS WIRE)--Pfizer Inc. (NYSE: PFE) announced today that the U.S. Food and Drug Administration (FDA) has approved the supplemental Biologics License Application (sBLA) for ADCETRIS® (brentuximab vedotin) in combination with lenalidomide and a rituximab product for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma (HGBL), after two or more lines of systemic therapy who are not eligible for autologous hematopoietic stem cell transplantation (auto-HSCT) or chimeric antigen receptor (CAR) T-cell therapy. "Each year, more than 3,500 patients in the U.S. with this aggressive form of non-Hodgkin lymphoma experience treatment failure or relapse after two prior lines of therapy," said Roger Dansey, M.D., Chief Oncology Officer, Pfizer. "Today's approval further reinforces the important role of ADCETRIS as an existing standard of care with overall survival improvement shown for certain types of lymphomas, and now allows physicians to have an option beyond chemotherapy or CAR-Ts for patients with relapsed/refractory large B-cell lymphoma." The approval is based on efficacy and safety data from the Phase 3 ECHELON-3 study, which demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) in patients with relapsed/refractory DLBCL who received ADCETRIS in combination with lenalidomide and rituximab. The study included patients who were heavily pre-treated, some of whom had received prior CAR-T therapy, and survival benefit was observed irrespective of CD30 expression. "Patients with large B-cell lymphoma can face a challenging journey, with too many patients enduring multiple rounds of chemotherapy and even CAR-T therapy with limited success," said principal investigator Dr. Craig Portell, Associate Professor, University of Virginia. "For patients who have previously faced setbacks with other therapies, ADCETRIS provides a new therapeutic option with outpatient administration and proven safety and efficacy." LBCL is a type of non-Hodgkin lymphoma (NHL), that affects immune cells called B lymphocytes, a type of white blood cell crucial to the body's immune system. DLBCL is the most common, aggressive and difficult-to-treat form of the disease. More than 25,000 cases of DLBCL are diagnosed each year in the United States, accounting for more than 25% of all lymphoma cases. Up to 40% of patients relapse or have refractory disease after frontline treatment, and more than 3,500 patients a year fail two prior lines of therapy and require third-line therapy. Despite recent treatment advances including bispecifics and CAR-T therapy, there remains a high unmet need for patients who are not eligible for these treatments or whose disease returns following treatment with these therapies. The ECHELON-3 study showed that the ADCETRIS combination reduced patients' risk of death by 37% compared to placebo in combination with lenalidomide and rituximab (HR 0.63 [95% CI: 0.445-0.891] p=0.0085). The OS benefit was consistent across levels of CD30 expression. Positive outcomes were also observed in key secondary endpoints, including overall response rate (ORR) and progression-free survival (PFS). The safety profile of ADCETRIS in ECHELON-3 was consistent with its known safety profile as presented in the U.S. prescribing information. The most frequently reported treatment-emergent adverse events (TEAEs) Grade 3 or higher for the ADCETRIS versus placebo arms were: neutropenia (43% vs 28%), thrombocytopenia (25% vs 19%) and anemia (22% vs 21%). Peripheral sensory neuropathy was infrequent and low grade for each arm with Grade 3 events of 4% vs 0%. Detailed data from ECHELON-3 were published in JCO Oncology Practice on January 7, 2025 and presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. About ECHELON-3 ECHELON-3 is an ongoing, randomized, double-blind, multicenter Phase 3 study evaluating ADCETRIS plus lenalidomide and rituximab versus lenalidomide and rituximab plus placebo in adult patients with relapsed/refractory or transformed DLBCL, regardless of CD30 expression, who have received two or more prior lines of therapy and are ineligible for stem cell transplant (HSCT) or CAR-T therapy. The study also includes patients with hard-to-treat subtypes with poorer outcomes including double hit/triple hit lymphoma and patients with transformed disease. Patients may be ineligible to receive either HSCT or CAR-T therapy due to co-morbidities or financial, geographic, insurance, manufacturing issues. In this global study, 230 patients were randomized across North America, Europe and Asia-Pacific. The primary endpoint is OS in the intent to treat population, with key secondary endpoints of PFS and ORR as assessed by investigator. Other secondary endpoints include complete response rate, duration of response, safety and tolerability. About Large B-cell Lymphoma LBCL accounts for about 1/3 of cases of NHL, a type of cancer that starts in the lymphocytes and affects immune cells called B lymphocytes. LBCL occurs most often in older people, with a median age of 67 at diagnosis. About 60-70% of people have advanced-stage disease when diagnosed, and up to 40% have disease that relapses or becomes refractory to initial therapy, and more than 3,500 patients a year fail two prior lines of therapy and require third-line therapy. DLBCL is the most common and aggressive type of LBCL and is difficult to treat. More than 25,000 cases of DLBCL are diagnosed each year in the United States, accounting for more than 25% of all lymphoma cases. DLBCL can develop spontaneously or as a result of diseases such as chronic lymphocytic lymphoma/small lymphocytic lymphoma, follicular lymphoma, or marginal zone lymphoma. About ADCETRIS More than 55,000 patients have been treated with ADCETRIS in the U.S. since its first U.S. approval in 2011, and more than 140,000 patients have been treated with ADCETRIS globally. ADCETRIS is an antibody-drug conjugate (ADC) comprised of a CD30-directed monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Pfizer's proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells. ADCETRIS is approved in eight indications in the U.S.: Adult patients with relapsed or refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) NOS, DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma (HGBL), after two or more lines of systemic therapy who are not eligible for auto-HSCT or chimeric antigen receptor (CAR) T-cell therapy, in combination with lenalidomide and a rituximab product (2025) Adult patients with previously untreated Stage III/IV classical Hodgkin lymphoma (cHL) in combination with doxorubicin, vinblastine, and dacarbazine (2018) Pediatric patients 2 years and older with previously untreated high risk cHL in combination with doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide (2022) Adult patients with cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation (2015) Adult patients with cHL after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates (2011) Adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone (2018) Adult patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. (2011) Adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) after prior systemic therapy (2017) Pfizer and Takeda jointly develop ADCETRIS. Under the terms of the collaboration agreement, Pfizer has U.S. and Canadian commercialization rights, and Takeda has rights to commercialize ADCETRIS in the rest of the world. Pfizer and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs. ADCETRIS® (brentuximab vedotin) for injection U.S. Important Safety Information BOXED WARNING PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML, and death can occur in ADCETRIS-treated patients. CONTRAINDICATION Contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation). WARNINGS AND PRECAUTIONS Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening PN may require a delay, change in dose, or discontinuation of ADCETRIS. Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid. Hematologic toxicities: Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS. Administer G-CSF primary prophylaxis beginning with Cycle 1 for adult patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL or relapsed or refractory LBCL and pediatric patients who receive ADCETRIS in combination with chemotherapy for previously untreated high risk cHL. Monitor complete blood counts prior to each ADCETRIS dose. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses. Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for infections. Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden may be at increased risk. Monitor closely and take appropriate measures. Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment. Avoid use in patients with severe renal impairment. Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment. Avoid use in patients with moderate or severe hepatic impairment. Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS. PML: Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed. Pulmonary toxicity: Fatal and serious events of noninfectious pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, have been reported. Monitor patients for signs and symptoms, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement. Serious dermatologic reactions: Fatal and serious cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy. Gastrointestinal (GI) complications: Fatal and serious cases of acute pancreatitis have been reported. Other fatal and serious GI complications include perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. Lymphoma with pre-existing GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, including severe abdominal pain, perform a prompt diagnostic evaluation and treat appropriately. Hyperglycemia: Serious cases, such as new-onset hyperglycemia, exacerbation of pre-existing diabetes mellitus, and ketoacidosis (including fatal outcomes) have been reported with ADCETRIS. Hyperglycemia occurred more frequently in patients with high body mass index or diabetes. Monitor serum glucose and if hyperglycemia develops, administer anti-hyperglycemic medications as clinically indicated. Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of this potential risk, and to use effective contraception during ADCETRIS treatment and for 2 months after the last dose of ADCETRIS. Advise male patients with female partners of reproductive potential to use effective contraception during ADCETRIS treatment and for 4 months after the last dose of ADCETRIS. ADVERSE REACTIONS The most common adverse reactions (≥20%) in adult patients are peripheral neuropathy, nausea, fatigue, musculoskeletal pain, constipation, diarrhea, vomiting, pyrexia, upper respiratory tract infection, mucositis, abdominal pain, and rash. The most common laboratory abnormalities (≥20%) in adult patients are decreased neutrophils, increased creatinine, decreased hemoglobin, decreased lymphocytes, increased glucose, increased ALT, and increased AST. The most common Grade ≥3 adverse reactions (≥5%) in combination with AVEPC in pediatric patients were neutropenia, anemia, thrombocytopenia, febrile neutropenia, stomatitis, and infection. DRUG INTERACTIONS Concomitant use of strong CYP3A4 inhibitors has the potential to affect the exposure to monomethyl auristatin E (MMAE). Closely monitor adverse reactions. USE IN SPECIAL POPULATIONS Lactation: Breastfeeding is not recommended during ADCETRIS treatment. Please see the full Prescribing Information, including BOXED WARNING, for ADCETRIS here. There may be a delay as the document is updated with the latest information. It will be available as soon as possible. Please check back for the updated full information shortly. About Pfizer Oncology At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world's most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives. About Pfizer: Breakthroughs That Change Patients' Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety, and value in the discovery, development, and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments, and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments, and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at In addition, to learn more, please visit us on and follow us on X at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Disclosure Notice The information contained in this release is as of February 12, 2025. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information about Pfizer Oncology and ADCETRIS (brentuximab vedotin), including its potential benefits, an approval in the U.S. for ADCETRIS in combination with lenalidomide and rituximab for adults with relapsed/refractory large B-cell lymphoma and the ongoing investigational trial for ADCETRIS in combination with lenalidomide and rituximab, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, uncertainties regarding the commercial success of ADCETRIS; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when drug applications may be filed in particular jurisdictions for ADCETRIS for any potential indications; whether and when any applications that may be pending or filed for ADCETRIS may be approved by regulatory authorities, which will depend on myriad factors, including making a determination as to whether the product's benefits outweigh its known risks and determination of the product's efficacy and, if approved, whether ADCETRIS will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of ADCETRIS; uncertainties regarding the impact of COVID-19 on Pfizer's business, operations and financial results; and competitive developments. A further description of risks and uncertainties can be found in Pfizer's Annual Report on Form 10-K for the fiscal year ended December 31, 2023 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned "Risk Factors" and "Forward-Looking Information and Factors That May Affect Future Results", as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at and View source version on Contacts Media Contact:+1 (212) 733-1226PfizerMediaRelations@ Investor Contact:+1 (212) 733-4848IR@ Sign in to access your portfolio
