Latest news with #glofitamab
Yahoo
23-05-2025
- Business
- Yahoo
New two-year follow-up of Roche's Columvi extends overall survival in relapsed or refractory diffuse large B-cell lymphoma patients
Updated data from the pivotal phase III STARGLO study continue to demonstrate a clinically meaningful improvement in overall survival with a 40% survival benefit for people with R/R DLBCL who are not candidates for transplant1 89% of patients whose cancer had fully responded at the end of treatment with Columvi in combination with chemotherapy were still alive and 82% showed no signs of cancer one year post-treatment1 Timely initiation of effective therapy at relapse or after initial therapy failure is critical for this aggressive, life-threatening disease Results demonstrate potential of the Columvi combination as a much-needed, off-the-shelf and fixed-duration treatment option Basel, 23 May 2025 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today two-year follow-up data from the phase III STARGLO study. After a median follow-up of 24.7 months, data showed a 40% improvement in overall survival (OS) for patients treated with Columvi® (glofitamab) in combination with gemcitabine and oxaliplatin (GemOx) and OS was not reached, compared to 13.5 months for MabThera®/Rituxan® (rituximab) plus GemOx (R-GemOx).1 These updated data continue to demonstrate the statistically significant and clinically meaningful survival benefit of this off-the-shelf, fixed-duration Columvi combination for people with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who have received at least one prior line of therapy and are not candidates for autologous stem cell transplant (ASCT).1 Data will be presented in an oral session at the 61st American Society of Clinical Oncology (ASCO), 30 May – 3 June 2025. 'We are encouraged that the two-year follow-up data for Columvi reinforces its potential to extend the lives of many patients where prognosis has historically been poor,' said Levi Garraway, MD, PhD, Roche's Chief Medical Officer and Head of Global Product Development. 'These findings demonstrate the potential lasting benefits of early and effective treatment initiation with a bispecific antibody for people with relapsed or refractory disease.' "When cancer comes back or doesn't respond to treatment, it's devastating for patients with DLBCL given the aggressive nature of the disease,' said Haifaa Abdulhaq, MD, Professor, University of California San Francisco (UCSF), Director of Hematology, UCSF Fresno. 'In my community practice, I've seen the potential of this Columvi combination to help patients start treatment quickly - providing lasting remissions and more time without ongoing therapy.' The benefit across key secondary endpoints, including progression-free survival (PFS) and complete remission (CR), was maintained for patients treated with the Columvi combination.1 There was a 59% reduction in the risk of disease progression or death (hazard ratio = 0.41, 95% confidence interval: 0.29–0.58) and more than twice as many patients sustained a CR (58.5% vs. 25.3%).1 Among patients with a CR at the end of the treatment period, 89% were alive and 82% had maintained remission one year after treatment.1 Safety of the combination remained unchanged from the previous analysis and was consistent with the known safety profiles of the individual medicines.1,2 Patients received a higher median number of cycles of the Columvi combination (11 versus 4), due to disease progression in the R-GemOx arm.1,2 A higher rate of adverse events (AEs) was observed with the Columvi regimen. One of the most common AEs was cytokine release syndrome, which was generally low grade.1 Given the wide adoption of global treatment guidelines in real-world clinical practice, there are no biological or clinical differences in DLBCL management worldwide.3-6 While second-line therapies have advanced, DLBCL can progress rapidly and many people are not candidates for, cannot tolerate, or do not have access to latest therapies.7,8 There is an urgent need for treatments that are rapidly available upon a diagnosis of relapse, that can manage the disease and improve long-term outcomes. Based on the STARGLO data, this Columvi combination is approved in more than 30 countries for people with R/R DLBCL who are not candidates for ASCT, including countries throughout the EU. Columvi in combination with GemOx was added to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as an NCCN category 1 preferred recommendation for the treatment of people with second-line DLBCL who are not intended to proceed to transplant.†3 Columvi monotherapy has been approved for use in R/R DLBCL after two or more prior lines of therapy in more than 60 countries worldwide. Columvi is part of Roche's industry-leading CD20xCD3 bispecific antibody programme. Together with the clinical development of off-the-shelf allogeneic CAR T-therapies, Roche aims to provide tailored treatment options that suit the diverse needs, preferences, and experiences of people with blood cancers and healthcare systems. About the STARGLO study The STARGLO study [GO41944; NCT04408638] is a phase III, multicentre, open-label, randomised study evaluating the efficacy and safety of Columvi® (glofitamab) in combination with gemcitabine plus oxaliplatin (GemOx) versus MabThera®/Rituxan® (rituximab) in combination with GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma who have received at least one prior line of therapy and who are not candidates for autologous stem cell transplant, or who have received two or more prior lines of therapy. Preclinical research indicated an increased antitumour effect when combining Columvi with GemOx over GemOx alone, so the STARGLO study was initiated to further explore the potential complementary effects of the treatment combination. Outcome measures include overall survival (primary endpoint), progression-free survival, complete response rate, objective response rate, duration of objective response (secondary endpoints), and safety and tolerability. About Columvi® (glofitamab) Columvi is a CD20xCD3 T-cell engaging bispecific antibody designed to target CD3 on the surface of T cells and CD20 on the surface of B cells. Columvi was designed with a novel 2:1 structural format. This T-cell engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T cells, a type of immune cell, and two regions that bind to CD20, a protein on B cells, which can be healthy or malignant. This dual-targeting brings the T cell in close proximity to the B cell, activating the release of cancer cell-killing proteins from the T cell. Columvi is part of Roche's broad and industry-leading CD20xCD3 T-cell-engaging bispecific antibody clinical development programme that also includes Lunsumio® (mosunetuzumab), which aims to provide tailored treatment options that suit the diverse needs, preferences, and experiences of people with blood cancers and healthcare systems. Roche is investigating Columvi as a monotherapy and in combination with other medicines for the treatment of diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma. As part of Roche's efforts to elevate treatment standards in the earlier stages of DLBCL, where there is the best opportunity to improve long-term outcomes and prevent relapse, Columvi is also being investigated in combination with Polivy® (polatuzumab vedotin) and MabThera®/Rituxan® (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) in previously untreated DLBCL in the phase III SKYGLO study [GO44145; NCT06047080]. About diffuse large B-cell lymphoma (DLBCL) DLBCL is an aggressive (fast-growing) type of non-Hodgkin lymphoma (NHL) and the most common form, accounting for about one in three cases of NHL.9 Approximately 160,000 people worldwide are diagnosed with DLBCL each year, with comparable incidence rates across regions.9,10 Medical practices, including pathological classification, diagnosis, staging, initial treatment and relapse management, are similarly approached worldwide.3-6 While it is generally responsive to treatment in the frontline, as many as 40% of people will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short.7,11 Improving treatments earlier in the course of the disease and providing much needed alternative options could help to improve long-term outcomes. About Roche in haematology Roche has been developing medicines for people with malignant and non-malignant blood diseases for more than 25 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera®/Rituxan® (rituximab), Gazyva®/Gazyvaro® (obinutuzumab), Polivy® (polatuzumab vedotin), Venclexta®/Venclyxto® (venetoclax) in collaboration with AbbVie, Hemlibra® (emicizumab), PiaSky® (crovalimab), Lunsumio® (mosunetuzumab) and Columvi® (glofitamab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibody cevostamab, targeting both FcRH5 and CD3 and Tecentriq® (atezolizumab). Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further. About Roche Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world's largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. For over 125 years, sustainability has been an integral part of Roche's business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit All trademarks used or mentioned in this release are protected by law. †NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. References[1] Abramson J, et al. Glofitamab plus gemcitabine and oxaliplatin (Glofit-GemOx) in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): 2-year (yr) follow-up of STARGLO. Presented at: ASCO Annual Meeting; 2025 May 30 - Jun 3. Abstract #7015.[2] Abramson J, et al. Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for relapsedor refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomised, open-label trial. Lancet2024; 404 (10466): 1940-1954.[3] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.1.2025.[4] Tilly H, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26:v116-25.[5] Zhu J, et al. Union for China Lymphoma Investigators of Chinese Society of Clinical Oncology. Chinese Society of Clinical Oncology (CSCO) diagnosis and treatment guidelines for malignant lymphoma 2021 (English version). Chin J Cancer Res. 2021;30;33(3):289-301.[6] Wight J, et al. Diffuse large B-cell lymphoma: a consensus practice statement from the Australasian Lymphoma Alliance. Intern Med J. 2022;52(9):1609-1623.[7] Fabbri N, et al. Second-line treatment of diffuse large B-cell lymphoma: Evolution of options. Semin Hematol2023; 60(5): 305–312.[8] Westin J, et al. CAR T cells as a second-line therapy for large B-cell lymphoma: A paradigm shift? Blood.2022;139(18):2737–2746.[9] UpToDate. Patient education: Diffuse large B cell lymphoma in adults (Beyond the Basics). [Internet; cited May2025]. Available from: World Health Organization. Numbers derived from GLOBOCAN 2022. Non-Hodgkin Lymphoma Factsheet[Internet; cited May 2025]. Available from: [11] Sehn LH, et al. Diffuse Large B-Cell Lymphoma. N Engl J Med. 2021;384(9):842-858. Roche Global Media Relations Phone: +41 61 688 8888 / e-mail: Hans Trees, PhD Phone: +41 79 407 72 58 Sileia Urech Phone: +41 79 935 81 48 Nathalie Altermatt Phone: +41 79 771 05 25 Lorena Corfas Phone: +41 79 568 24 95 Simon Goldsborough Phone: +44 797 32 72 915 Karsten Kleine Phone: +41 79 461 86 83 Nina Mählitz Phone: +41 79 327 54 74 Kirti Pandey Phone: +49 172 6367262 Yvette Petillon Phone: +41 79 961 92 50 Dr Rebekka Schnell Phone: +41 79 205 27 03 Roche Investor Relations Dr Bruno Eschli Phone: +41 61 68-75284 e-mail: Dr Sabine Borngräber Phone: +41 61 68-88027 e-mail: Dr Birgit Masjost Phone: +41 61 68-84814 e-mail: Investor Relations North America Loren Kalm Phone: +1 650 225 3217 e-mail: Attachment 23052025_Columvi_phase III STARGLO_enError in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
Medscape
22-05-2025
- Business
- Medscape
FDA Advisory: Daratumumab Wins, Glofitamab Loses
Daratumumab and hyaluronidase (Darzalex Faspro, Johnson & Johnson) came a step closer to being approved for high-risk smoldering multiple myeloma (SMM) on Tuesday after the Oncologic Drugs Advisory Committee (ODAC) of the US Food and Drug Administration (FDA) voted that the benefits outweigh the risks. However, the prospects of glofitamab (Columvi, Roche) for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) dimmed after the committee agreed with the FDA that the results of a trial, which was conducted largely in Asia, are not really applicable to patients in the United States. Daratumumab and hyaluronidase (DARA SC) is already on the US market as a standard first-line option for MM, but there's currently no approved medication for SMM, an MM precursor. Standard treatment for SMM is either watchful waiting or referral to a clinical trial. Glofitamab, meanwhile, has accelerated approval as monotherapy in the third or later lines for R/R DLBCL. Roche was hoping to move it to an earlier line of treatment in combination with gemcitabine and oxaliplatin for transplant-ineligible disease. The FDA called the hearing because it had concerns about the trials supporting the two applications, AQUILA in the case of DARA SC and STARGLO for glofitamab. STARGLO in the United States STARGLO evaluated substituting glofitamab for rituximab on a background of gemcitabine and oxaliplatin for transplant-ineligible R/R DLBCL, not otherwise specified, following at least one line of systemic therapy. There was a statistically significant improvement in overall survival (OS), progression-free survival (PFS), and complete response (CR) with glofitamab across 274 patients. The main concern the FDA had with the trial is that almost half of the patients were from Korea, Taiwan, and China, and there were only 25 US patients. Others came from Europe and Australia. When the FDA compared outcomes of Asian vs non-Asian patients, it found significant differences. Despite a strong hazard ratio (HR) for OS benefit in Asia (HR, 0.39), there was a trend toward worse OS in Europe and the United States and in White patients, with similar trends for worse PFS and CR rates. The reasons aren't clear. 'FDA is concerned by the lack of internal consistency observed in the STARGLO trial and how the results of the Asian region appear to be driving the overall trial results,' the agency said in meeting documents. 'The low enrollment of patients in the US limits the agency's ability to assess the applicability of the study results to a US patient population,' the FDA said in meeting documents. 'Furthermore, the FDA has identified multiple differences in patient-related, disease-related, and healthcare system–related factors between the non-Asian and Asian regional subgroup populations. Taken together, these issues raise uncertainty as to whether the results…are generalizable and applicable to a US patient population,' the agency said. Among other concerns, the FDA also noted that rituximab/gemcitabine/oxaliplatin wasn't a good comparator arm for US patients because the regimen is not commonly used in the United States, which might have contributed to low enrollment at US study sites. Trial sponsor Roche highlighted the overall outcomes and that there's an unmet need for additional DLBCL treatment options. Company representatives also said that outside of Asia, patients on glofitamab had a higher risk for disease than those on rituximab, and rituximab patients were more likely to subsequently receive new anti-lymphoma therapy like CAR T cells. It pinned the low US enrollment on COVID disruptions during the pandemic. In the end, ODAC sided with the agency, voting 8 to 1 that the trial results are not applicable to US patients. Echoing many committee members, panelist Heidi McKean, MD, community oncologist in Sioux Falls, South Dakota, said she voted that the trials wasn't applicable 'due to the inconsistencies in the results…and quite frankly, more patients in the US need to be looked at to prove efficacy and safety.' Richard Pazdur, MD, director of the FDA's Oncology Center of Excellence, said these issues in STARGLO aren't uncommon. 'Unfortunately, if you take a look at all the oncology trials that come to us, only about 20% of the population is derived from the United States. We'd like to understand the reasons why sites are not enrolling in the United States. Potentially, that could be lack of interest because many times the control arms are not appropriate for a US population,' he said. 'This is going to be an area that the Oncology Center of Excellence is looking at quite closely. People are developing drugs for marketing in the United States, so it should address our interest here in the United States,' he said. A Win for DARA SC ODAC also considered the AQUILA trial, which randomized 390 patients with SMM at a high risk for progression to MM to either DARA SC or active monitoring for up to 3 years. At a median follow-up of 65.2 months, the risk for disease progression or death was 51% lower with DARA SC than with active monitoring. At 5 years, PFS was 63.1% with DARA SC and 40.8% with active monitoring, and OS was 93.0% with DARA SC and 86.9% with active monitoring, although the trial was not adequately powered to demonstrate a significant improvement in OS. The positive results were countered by a higher incidence of grade 3/4 treatment emergent adverse events with DARA SC, 40% vs 30%. The FDA's primary concern was that the trial, which was designed almost 10 years ago, used an outdated model to select patients at high risk for progression. With current risk models, only 41% of participants would be categorized as high risk, with 39% considered intermediate risk and 20% as low risk. 'This raises concerns regarding the applicability of the trial results to a population with high-risk SMM, as currently defined,' the FDA said in meeting materials. Also, 'while the trial met its primary PFS endpoint, there is uncertainty in the benefit of delaying progression to [multiple myeloma] in the absence of a significant improvement in OS. Additionally, the observed difference in progression was primarily due to differences observed in the biochemical or lab parameters,' not the onset of symptomatic disease, the FDA said. Not all high-risk patients progress to MM, so the agency also had concerns about unnecessary treatment — particularly with the elevated risk for serious and high-grade adverse events with daratumumab. 'Given the limitations of the clinical meaningfulness of the efficacy findings and the toxicity observed with 3 years of treatment with Dara SC, there is uncertainty regarding the benefit-risk profile of Dara SC for patients with high-risk SMM,' the agency said. Johnson and Johnson countered by emphasizing that all of the trials endpoints are positive, and that without an approved medication for SMM, patients are left powerless as they wait for a MM to emerge, something a commenter likened to 'sitting on a ticking time bomb.' Vincent Rajkumar, MD, myeloma specialist at the Mayo Clinic in Rochester, Minnesota, presenting on behalf of the company, also caught the attention of panelists when he said that high-risk SMM isn't simply a benign precursor to MM, but rather cancer in itself, raising the stakes for early intervention. 'It is asymptomatic, but not premalignant. It is cancer. Genomically, [it is] indistinguishable from multiple myeloma,' he said. In the end, the company's arguments won the day. ODAC voted 6 to 2 that AQUILA provide sufficient evidence to support a favorable risk-benefit profile for DARA SC for SMM. 'The shift for me was thinking of smoldering multiple myeloma as a malignancy and allowing the physician and patient to look at this data and intervene earlier if they so choose,' McKean said. Another committee member, Christopher Lieu, MD, gastrointestinal medical oncologist at the University of Colorado Cancer Center, Aurora, Colorado, agreed. 'I really want patients and providers to have the option to discuss this, to have the benefit-risk discussion. The conversation includes the fact that there are toxicities from this drug; that there's a chance that you can prevent a life-altering fracture; that you might be able to prevent or delay at least the onset of treatment; that you might be able to delay or prevent an organ damage. I think that that is a conversation that I want patients and providers to have the option to have,' Lieu said. However, this is going to lead to overtreatment. There has to be a predictive biomarker or some type of risk stratification to refine this high-risk group,' he said. The FDA usually follows the advice of its advisory committees.
