Latest news with #DLBCL
Medscape
2 days ago
- Health
- Medscape
Can New Biomarker Help Identify High-Risk DLBCL Patients?
For patients with diffuse large B-cell lymphoma (DLBCL), the detection of circulating tumor DNA (ctDNA) following first-line treatment is independently predictive of disease recurrence and overall survival over 2 years, suggesting important prognostic value of the biomarker to improve upon standard assessment with PET-CT imaging. 'We demonstrated the prognostic value of ctDNA MRD [minimal residual disease] in first-line DLBCL cell patients [and that] ctDNA MRD provides independent evidence of residual disease beyond PET-CT,' said first author Steven Wang, MD, of Amsterdam UMC Location Vrije Universiteit, Amsterdam, the Netherlands, in presenting the findings at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. 'These results support the integration of ctDNA MRD as a standard component of response evaluation in first-line DLBCL treatment,' he said. The prognosis for long-term outcomes in DLBCL currently relies on PET-CT; however, key challenges with the approach include sometimes suboptimal sensitivity and specificity, with the potential to miss microscopic residual disease. Liquid biopsy-based analysis of ctDNA, increasingly used in other cancers, meanwhile offers a radiation-free, non-invasive method for the assessment and monitoring of DLBCL. To further investigate the biomarker's prognostic benefits in DLBCL in a prospective context, Wang and colleagues evaluated data on 160 patients at more than 50 centers in the Netherlands and Belgium in the HOVON-902 trial. Of the patients, most (79%) had stage 3 or 4 disease. All patients had been treated with curative-intent first-line therapy, with either R-CHOP or DA-EPOCH-R chemotherapy regimens. In the assessment of ctDNA MRD, the investigators utilized the phased variant (PV) enrichment and detection sequencing (PhasED-Seq) assay, which targets unique 'phased variant' alterations, or multiple mutations on the same DNA molecule. The design boosts the assay's sensitivity compared with other tests, which can have limitations such as error profiles of single nucleotide variants (SNVs). Among the patients, most (90%) had DLBCL, with 9% having high-grade B-cell lymphoma and 1% with primary mediastinal large B-cell lymphoma. In terms of the distribution of International Prognostic Index (IPI) risk level, 22% were low-risk, 29% low-intermediate risk, 27% high-intermediate risk, and 22% at high-risk. Patients' median age was 67.5 years. With 31 months of median follow-up in the cohort overall, the 24-month rates of progression-free survival (PFS) and overall survival (OS) were 74% and 86%, respectively. The rates of PFS after 3 years were substantially higher for those who were MRD-negative at the end of treatment compared with those who were MRD-positive (85% vs 15%, respectively; hazard ratio [HR] 11.03; P < .0001), and 3-year rates of OS were also higher (92% vs 41%; HR, 7.38; P < .0001). The findings show that 'end-of-treatment ctDNA MRD is strongly prognostic for PFS and OS,' Wang said. Higher cancer stage and IPI risk were associated with MRD positivity (both P < .05), and ctDNA was the most strongly prognostic of PFS (HR, 11.03), compared with end-of-treatment PET-CT results (HR, 5.31) or IPI level of risk (HR, 1.61). Of patients who did not have a complete response based on PET results, MRD-positivity was likewise significantly prognostic for worse PFS at 3 years (PFS 4%) compared with those who were MRD-negative (PFS 64%), importantly suggesting the ability of MRD to adjudicate imaging results (HR for PFS, 6.78; P < .0001). 'End of treatment ctDNA MRD-positivity in patients without complete response have especially poor outcomes,' Wang noted. All of the patients who did not achieve a complete molecular response and remained MRD-positive experienced a relapse. The prognostic accuracy of ctDNA-MRD status was observed across subgroups, including based on the source of baseline sample (tumor vs plasma), best clinical response, IPI, sex, lactate dehydrogenase, stage, or extranodal disease. The researchers also examined how ctDNA MRD status at the end of treatment correlated with the timing of response, and they found that 80% of patients who relapsed within a year of treatment had positive ctDNA MRD at the end of treatment, while only 22% of patients who relapsed after the first 12 months of first-line therapy had positive MRD. 'This distinction is important as early relapsers might be eligible for CAR T-cell therapy, and this demonstrates that end of treatment ctDNA MRD can reliably predict early relapses; however, long late relapses might require longitudinal MRD monitoring,' Wang explained. 'These data demonstrate the robust prognostic value of ctDNA MRD by PhasED-Seq in first-line DLBCL patients,' Wang said. ctDNA Risk-Stratification Benefits Important Discussing the research at the meeting, Mark Roschewski, MD, of the National Cancer Institute, Bethesda, Maryland, agreed that results on the timing of events were notably important. 'Now we can have a better understanding of when these events get captured [on ctDNA testing] and what we saw is that mostly these are early events,' said Roschewski, who recently co-authored a review of ctDNA as measurable residual disease in aggressive B-cell lymphoma. Roschewski noted that the benefits of ctDNA are reflected in changes in National Comprehensive Cancer Network (NCCN) Guidelines, which indicate that ctDNA, using a sufficient test — such as PhasED Seq — does appear to be suitable as an alternative to invasive tissue biopsies for positive PET scans. However, the most important thing that the research shows — which validates other findings — is that 'these tests can actually risk-stratify patients who have positive as well as negative PET scans, improving upon our current definition of remission,' Roschewski added. Ultimately, the findings show that 'ultrasensitive ctDNA at the end of frontline therapy for large B-cell lymphoma is the most precise tool to define remission,' he said. Not Ready for Prime Time? However, for all of its promising benefits, a key concern expressed in the Q&A portion of the session was whether ctDNA could indeed be relied upon to replace a tissue biopsy in real-world practice. For instance, while a positive PET scan and positive ctDNA MRD result could likely give clinicians confidence in moving ahead with second-line therapy, the approach may be less clear if a patient is PET-negative but MRD-positive. 'What I worry about is that [ctDNA] is prognostic, but not predictive, and with a relatively small dataset in this study, what are the implications in terms of overtreatment in that kind of situation?' one audience member noted. 'This is an important point,' responded Roschewski. 'However, we should recognize that with the way things are done now, our PET scans have a positive predictive value of about 50%,' he said. 'One of the concerns, and we see it in the data, is that these patients with a positive PET scan are getting second-line therapy when they don't even have any active disease.' 'So, this is something that is already happening,' he explained. Guidelines in such situations suggest either repeating the PET scan or the biopsy, hence delaying therapy. 'So, a negative ctDNA test could help you get information sooner,' Roschewski said. 'But would it improve patient outcomes?' the audience member pressed, getting to the issue of clinical utility. 'That's something we don't have data on yet,' Roschewski conceded. 'I completely agree that this may not be ready for general clinical care without that data, but it may be fine in the context of a clinical trial for now.' Roschewski noted that the good news is that 'at least three clinical trials' are currently being planned to address the issues. He noted that 'we are able to [use this] in other hemolytic malignancies, but we have not gotten there yet [with DLBCL] and we need prospective trials to tell us what to do.' The encouraging news, however, is 'if we see success here, there is no reason to stop at large cell lymphoma. There are other curable lymphomas that we would like to test this in, and I think this could be a domino effect in which we start thinking about this all across therapies for a bunch of different lymphomas,' Roschewski said. ctDNA Benefits in Early Disease Assessment Anticipated Jane N. Winter, MD, professor of medicine, Division of Hematology/Oncology, Northwestern University, Chicago, Illinois, agreed that, with the data showing that ct-DNA is a powerful predictor of clinical outcome and can identify patients at high risk of relapse, 'the big question is how we should use this information.' For instance, 'how important is it to identify refractory disease immediately at the end-of-treatment?' she said in an interview. 'I'm hopeful that ctDNA kinetics early in the course of therapy can help us identify patients for escalation of therapy,' said Winter, a past president of the American Society of Hematology. 'Similarly, we might be able to use ctDNA to deescalate or abbreviate therapy.' Ultimately, the results underscore that 'ctDNA at the end of treatment is a powerful predictor of progression/relapse,' Winter said. 'I'm very interested in using ctDNA as part of an early disease assessment.'
Yahoo
3 days ago
- Business
- Yahoo
ASCO25: MSD's ADC candidate achieves 56.3% ORR in lymphoma trial
Zilovertamab vedotin, an antibody drug conjugate (ADC) developed by Merck & Co (MSD) to treat diffuse large B-cell lymphoma (DLBCL), has demonstrated promise in a Phase II/III study, as the company looks to catch up with ADC Therapeutics' marketed drug. When administered in combination with standard of care, rituximab and gemcitabine-oxaliplatin (R-GemOx), zilovertamab vedotin achieved an objective response rate (ORR) of 56.3%. At this pre-planned analysis, there were eight complete responses (CR) and one partial response (PR). The median follow-up in this 1.75mg/kg cohort was 9.9 months. ADC Therapeutics' Zynlonta (loncastuximab tesirine-lpyl) is the only ADC approved by the US Food and Drug Administration (FDA) for DLBCL. In the Phase II LOTIS-2 trial, Zynlonta – administered as a monotherapy – produced an ORR of 48.3%. MSD published a snapshot of the results from the ongoing waveLINE-003 study (NCT05139017) ahead of a presentation on 30 May at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, held from 30 May to 3 June in Chicago, Illinois. The positive efficacy results came despite a patient dying in the highest dose cohort due to treatment-related sepsis. MSD's randomised, multicenter, open-label, dose confirmation and expansion waveLINE-003 study is investigating the zilovertamab vedotin triplet combination therapy as a treatment for relapsed or refractory DLBCL. Patients with blood cancer who have already tried one more line of therapy are eligible for the treatment, administered intravenously every three weeks up to six cycles at three different doses. MSD disclosed that treatment-related adverse events (TRAEs) were reported in 98% of patients (n=40), with those at Grade 3 or higher occurring in 63% of patients. At the highest dose of 2.0mg/kg, three patients discontinued treatment due to adverse events, one patient withdrew due to a physician's decision, and one patient died after discontinuing treatment due to related sepsis. At this dose, three patients completed the treatment, compared to the eight from the 1.75mg/kg dose. MSD said that based on safety and efficacy data, the recommended Phase II dose is 1.75g/kg. Zilovertamab vedotin is an ADC that targets ROR1, which is a transmembrane protein overexpressed in multiple haematologic malignancies. The ADC market was valued at $8.6bn in 2023, with it forecast to exceed $45bn by 2030, according to analysis by GlobalData. MSD's data arrived on the same day that Germany-based Merck KGaA, also presenting at ASCO, revealed positive Phase I results for its ADC candidate for metastatic colorectal cancer treatment. GlobalData is the parent company of Pharmaceutical Technology. MSD Research Laboratories' oncology clinical research vice president Dr Gregory Lubiniecki said: 'In the Phase II portion of the waveLINE-003 trial, the 1.75mg/kg dose of zilovertamab vedotin with rituximab, gemcitabine and oxaliplatin demonstrated a promising response rate, complete response rate and manageable safety profile in combination with standard of care. 'The Phase III portion of this trial is already enrolling, and as we continue to advance our research of this investigational ROR1-directed ADC, these promising results amplify our belief in the potential of zilovertamab vedotin to treat multiple hematologic malignancies.' Zilovertamab vedotin is also currently being evaluated in patients with previously untreated DLBCL in the Phase III waveLINE-010 study (NCT06717347) and the Phase II waveLINE-007 study (NCT05406401). ADC content on Pharmaceutical Technology (Or Clinical Trials Arena) is supported by Syngene. Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. "ASCO25: MSD's ADC candidate achieves 56.3% ORR in lymphoma trial" was originally created and published by Clinical Trials Arena, a GlobalData owned brand. The information on this site has been included in good faith for general informational purposes only. It is not intended to amount to advice on which you should rely, and we give no representation, warranty or guarantee, whether express or implied as to its accuracy or completeness. You must obtain professional or specialist advice before taking, or refraining from, any action on the basis of the content on our site. Error 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
Business Wire
4 days ago
- Business
- Business Wire
Merck's Investigational Zilovertamab Vedotin at 1.75 mg/kg Dose Plus Standard of Care Showed Promising Antitumor Activity, Including Complete Response Rate, in Patients With Relapsed/Refractory DLBCL in Phase 2 Portion of waveLINE-003 Trial
RAHWAY, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced results from the dose confirmation portion of the Phase 2/3 waveLINE-003 study evaluating zilovertamab vedotin in combination with standard of care rituximab and gemcitabine-oxaliplatin (R-GemOx) for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Zilovertamab vedotin is an investigational, potential first-in-class antibody drug conjugate (ADC) that targets receptor tyrosine kinase-like orphan receptor 1 (ROR1). At a pre-planned analysis, zilovertamab vedotin 1.75 mg/kg in combination with R-GemOx achieved a 56.3% objective response rate (ORR) in patients with relapsed or refractory DLBCL (n=16), with eight complete responses (CR) and one partial response (PR). These data are being presented for the first time today during an oral presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #7005). 'Patients with relapsed or refractory diffuse large B-cell lymphoma continue to experience poor outcomes and an unmet need remains to help provide these patients with additional options to treat their cancer,' said Dr. Philippe Armand, the study's principal investigator, Dana-Farber Cancer Institute. 'These data from the Phase 2 portion of the waveLINE-003 trial are encouraging for patients and support further research in the relapsed/refractory setting in a larger patient population.' 'In the Phase 2 portion of the waveLINE-003 trial, the 1.75 mg/kg dose of zilovertamab vedotin with rituximab, gemcitabine and oxaliplatin demonstrated a promising response rate, complete response rate and manageable safety profile in combination with standard of care,' said Dr. Gregory Lubiniecki, vice president, oncology clinical research, Merck Research Laboratories. 'The Phase 3 portion of this trial is already enrolling, and as we continue to advance our research of this investigational ROR1-directed ADC, these promising results amplify our belief in the potential of zilovertamab vedotin to treat multiple hematologic malignancies.' Zilovertamab vedotin is currently being evaluated in patients with previously untreated DLBCL in the Phase 3 waveLINE-010 study (NCT06717347) and in the Phase 2 waveLINE-007 study (NCT05406401). Additionally, we recently initiated the Phase 2 waveLINE-011 study (NCT06890884), which is a randomized, open-label clinical trial evaluating zilovertamab vedotin plus rituximab and cyclophosphamide, doxorubicin and prednisone (R-CHP) versus polatuzumab vedotin with R-CHP for the treatment of patients with DLBCL. The trial is estimated to enroll 594 patients and the primary endpoint is CR rate at end of treatment, with secondary endpoints of progression-free survival (PFS), overall survival (OS), event-free survival, duration of CR and safety. Global recruitment of the waveLINE-011 study has begun, with patients now enrolling. As announced, data spanning more than 25 types of cancer are being presented from Merck's broad oncology portfolio and investigational pipeline at the 2025 ASCO Annual Meeting. Study design and additional data from waveLINE-003 WaveLINE-003 is a Phase 2/3 randomized, multicenter, open-label, dose confirmation and expansion clinical trial ( NCT05139017) designed to assess the safety and efficacy of zilovertamab vedotin in combination with standard of care options for the treatment of relapsed or refractory DLBCL after one or more lines of therapy. This study is divided into two parts: dose confirmation (part 1) and efficacy expansion (part 2) and enrolled adult participants with confirmed relapsed or refractory DLBCL after one or more lines of therapy and an Eastern Cooperative Oncology Group performance status of 0-2. In Part 1, primary endpoints were safety and recommended Phase 2 dose (RP2D). Secondary endpoints were ORR, duration of response (DOR) per Lugano 2014 response criteria by blinded independent central review and OS. Part 1 of the trial enrolled 40 patients (as of the August 1, 2024 data cutoff) to receive either: Zilovertamab vedotin (1.5 mg/kg intravenously [IV]) plus rituximab (375 mg/m 2 IV), gemcitabine (1000 mg/m 2 IV) and oxaliplatin (100 mg/m 2 IV), given every three weeks (Q3W) up to six cycles (n=17), or Zilovertamab vedotin (1.75 mg/kg IV) plus R-GemOx Q3W up to six cycles (n=16), or Zilovertamab vedotin (2.0 mg/kg IV) plus R-GemOx Q3W up to six cycles (n=7). Treatment-related adverse events (TRAEs) were reported in 98% of patients (n=40). Grade ≥3 TRAEs occurred in 63% of patients (n=25). At the 1.5 mg/kg dose of zilovertamab vedotin plus R-GemOx, four patients completed treatment, eight discontinued due to progression and one withdrew, with four patients receiving ongoing treatment at data cut-off. At the 1.75 mg/kg dose, eight patients completed treatment, seven discontinued due to progression and one patient discontinued due to physician decision. In the 2.0 mg/kg dose cohort, three patients completed treatment, three patients discontinued treatment due to adverse events (AEs) (treatment-related sepsis and respiratory failure), and one patient withdrew due to physician decision. One patient died after discontinuing treatment due to treatment-related sepsis. The most common AEs were diarrhea, nausea, anemia and platelet count decrease, while the most common Grade ≥3 AEs were neutropenia, neutrophil count decrease, platelet count decrease and anemia. Seven dose-limiting toxicities occurred across all participants. At the 1.5 mg/kg dose of zilovertamab vedotin plus R-GemOx, one participant had Grade 4 febrile neutropenia. At the 1.75 mg/kg dose, one participant experienced Grade 3 alanine aminotransferase increased and one patient had intestinal obstruction. At the 2.0 mg/kg dose, participants had Grade 3 diarrhea, Grade 4 neutrophil count decrease and Grade 4 thrombocytopenia (one patient each), and one patient experienced both Grade 3 febrile neutropenia and Grade 4 neutrophil count decrease. The median follow-up for all participants was 9.8 months. At a median follow-up of 18.1 months (range, 2.4 to 23.3 months) in patients receiving the 1.5 mg/kg dose of zilovertamab vedotin (n=15), ORR was 26.7% (3 CR [20.0%], 1 PR [6.7%]) and median DOR was 14.4 months (95% CI, not reached [NR]-NR). At a median follow-up of 9.9 months (range, 4.0 to 30.0 months) for patients receiving the 1.75 mg/kg dose (n=16), ORR was 56.3% (8 CR [50.0%], 1 PR [6.3%]) and median DOR was 8.7 months (95% CI, 2.3-NR). At a median follow-up of 9.3 months (range, 6.0 to 10.0 months) for patients receiving the 2.0 mg/kg dose (n=7), the ORR was 57.1% (3 CR [42.9%], 1 PR [14.3%]) and median DOR was not reached (95% CI, 4.1-NR). Based on these results and accompanying safety data, the recommended Phase 2 dose of zilovertamab vedotin was determined to be 1.75 mg/kg when used with R-GemOx. About diffuse large B-cell lymphoma Lymphoma is cancer beginning in the lymphatic system – the network of organs, vessels and tissues that protects the body from infection. There are many subtypes of lymphoma, which is often categorized into two main types – Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma, the most common form of NHL, is derived from white blood cells that grow rapidly and uncontrollably, enlarging the lymph nodes and often migrating to other parts of the body. DLBCL accounts for approximately 25-30% of all NHLs worldwide. In the U.S., it is estimated that approximately 25,000 patients are diagnosed with DLBCL each year. The five-year relative survival rate for DLBCL is 60-70%. About zilovertamab vedotin (MK-2140) Zilovertamab vedotin is an investigational, potential first-in-class ADC that targets ROR1. ROR1 is a transmembrane protein that is overexpressed in multiple hematologic malignancies. Merck is committed to research with zilovertamab vedotin across B-cell malignancies and has established a robust program of clinical trials under the name waveLINE. In addition to waveLINE-003, the waveLINE program includes a Phase 3 study in patients with previously untreated DLBCL (waveLINE-010, NCT06717347), a Phase 2 study in patients with select B-cell lymphomas (waveLINE-006, NCT05458297), a Phase 2 study in patients with germinal center B-cell-like DLBCL (waveLINE-011, NCT06890884) and a Phase 2 study in patients with previously untreated DLBCL (waveLINE-007, NCT05406401). About Merck in hematology Merck is committed to advancing innovation and care for people with hematologic neoplasms and malignancies. Building on its leadership in oncology, the company has a broad clinical development program that evaluates novel mechanisms of action to address longstanding unmet needs for patients with hematologic disorders. Among Merck's research efforts are studies evaluating multiple investigational medicines as monotherapy or in combination with other therapies across a range of hematologic neoplasms and malignancies. Merck's focus on cancer Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn. Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the 'company') includes 'forward-looking statements' within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company's management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company's Annual Report on Form 10-K for the year ended December 31, 2024 and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site (
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
Business Wire
23-05-2025
- Business
- Business Wire
New Two-year Follow-up of Genentech's Columvi Extends Overall Survival in Relapsed or Refractory Diffuse Large B-cell Lymphoma Patients
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (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-gxbm) in combination with gemcitabine and oxaliplatin (GemOx) and median OS was not reached, compared to 13.5 months for Rituxan ® (rituximab) plus GemOx (R-GemOx). 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). Data will be presented in an oral session at the 61st American Society of Clinical Oncology (ASCO), May 30 – June 3, 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, M.D., Ph.D., 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, M.D., 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. 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%). Among patients with a CR at the end of the treatment period, 89% were alive and 82% had maintained remission one year after treatment. Safety of the combination remained unchanged from the previous analysis and was consistent with the known safety profiles of the individual medicines. Patients received a higher median number of cycles of the Columvi combination (11 versus 4), due to disease progression in the R-GemOx arm. 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. Given the wide adoption of global treatment guidelines in real-world clinical practice, there are no biological or clinical differences in DLBCL management worldwide. 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. 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. † 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 Genentech's industry-leading CD20xCD3 bispecific antibody program. Together with the clinical development of off-the-shelf allogeneic CAR T-therapies, Genentech aims to provide tailored treatment options that suit the diverse needs, preferences, and experiences of people with blood cancers and healthcare systems. † 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. About the STARGLO study The STARGLO study [GO41944; NCT04408638] is a Phase III, multicenter, open-label, randomized study evaluating the efficacy and safety of Columvi ® (glofitamab-gxbm) in combination with gemcitabine plus oxaliplatin (GemOx) versus 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 antitumor 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-gxbm) 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 Genentech's broad and industry-leading CD20xCD3 T-cell-engaging bispecific antibody clinical development program, which aims to provide tailored treatment options that suit the diverse needs, preferences, and experiences of people with blood cancers and healthcare systems. Genentech 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 Genentech'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 other medicines in previously untreated DLBCL in the Phase III SKYGLO study [GO44145; NCT06047080 ]. About Diffuse Large B-Cell Lymphoma Diffuse large B-cell lymphoma (DLBCL) is an aggressive (fast-growing) blood cancer and is the most common form of non-Hodgkin's lymphoma in the U.S. Approximately 160,000 people worldwide are diagnosed with DLBCL each year, with comparable incidence rates across regions. Medical practices, including pathological classification, diagnosis, staging, initial treatment and relapse management, are similarly approached worldwide. 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. Improving treatments earlier in the course of the disease and providing much-needed alternative options could help to improve long-term outcomes. Columvi U.S. Indication Columvi (glofitamab-gxbm) is a prescription medicine to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) or large B-cell lymphoma (LBCL) that has come back (relapsed) or that did not respond to previous treatment (refractory), and who have received 2 or more prior treatments for their cancer. It is not known if Columvi is safe and effective in children. The conditional approval of Columvi is based on response rate and durability of response. There are ongoing studies to establish how well the drug works. What is the most important information I should know about Columvi? Columvi can cause Cytokine Release Syndrome (CRS), a serious side effect that is common during treatment with Columvi, and can also be serious and lead to death. Call your healthcare provider or get emergency medical help right away if you develop any signs or symptoms of CRS, including: fever of 100.4°F (38°C) or higher chills or shaking fast or irregular heartbeat dizziness or light-headedness trouble breathing shortness of breath Due to the risk of CRS, you will receive Columvi on a 'step-up dosing schedule'. A single dose of a medicine called obinutuzumab will be given to you on the first day of your first treatment cycle (Day 1 of Cycle 1). You will start the Columvi step-up dosing schedule a week after the obinutuzumab dose. The step-up dosing schedule is when you receive smaller 'step-up' doses of Columvi on Day 8 and Day 15 of Cycle 1. This is to help reduce your risk of CRS. You should be hospitalized during your infusion and for 24 hours after receiving the first step-up dose on Day 8. You should be hospitalized during your infusion and for 24 hours after receiving the second step-up dose on Day 15 if you experienced CRS during the first step-up dose. You will receive your first full dose of Columvi a week after the second step-up dose (this will be Day 1 of Cycle 2). If your dose of Columvi is delayed for any reason, you may need to repeat the 'step-up dosing schedule'. If you had more than mild CRS with your previous dose of Columvi, you should be hospitalized during and for 24 hours after receiving your next dose of Columvi. Before each dose of Columvi, you will receive medicines to help reduce your risk of CRS and infusion-related reactions. Your healthcare provider will monitor you for CRS during treatment with Columvi and may treat you in a hospital if you develop signs and symptoms of CRS. Your healthcare provider may temporarily stop or completely stop your treatment with Columvi if you have severe side effects. Carry the Columvi Patient Wallet Card with you at all times and show it to all of your healthcare providers. The Columvi Patient Wallet Card lists the signs and symptoms of CRS you should get emergency medical help for right away. What are the possible side effects of Columvi? Columvi may cause serious side effects, including: Cytokine Release Syndrome. Neurologic problems. Columvi can cause serious neurologic problems that may lead to death. Your healthcare provider will monitor you for neurologic problems during treatment with Columvi. Your healthcare provider may also refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any signs or symptoms of neurologic problems, including: headache confusion and disorientation difficulty paying attention or understanding things trouble speaking sleepiness memory problems numbness, tingling, or weakness of the hands or feet dizziness shaking (tremors) Serious Infections. Columvi can cause serious infections that may lead to death. Your healthcare provider will monitor you for signs and symptoms of infection and treat you as needed. Tell your healthcare provider right away if you develop any signs of an infection, including: fever, chills, weakness, cough, shortness of breath, or sore throat. Growth in your tumor or worsening of tumor related problems (tumor flare). Tell your healthcare provider if you get any of these signs or symptoms of tumor flare: tender or swollen lymph nodes pain or swelling at the site of the tumor chest pain cough trouble breathing The most common side effects of Columvi include: CRS, muscle and bone pain, rash, and tiredness. The most common severe abnormal lab test results with Columvi include: decreased white blood cells, decreased phosphate (an electrolyte), increased uric acid levels, and decreased fibrinogen (a protein that helps with blood clotting). Your healthcare provider may temporarily stop or completely stop treatment with Columvi if you develop certain side effects. Before receiving Columvi, tell your healthcare provider about all of your medical conditions, including if you: have an infection have kidney problems are pregnant or plan to become pregnant. Columvi may harm your unborn baby Females who are able to become pregnant: Your healthcare provider should do a pregnancy test before you start treatment with Columvi. You should use effective birth control (contraception) during treatment and for 1 month after your last dose of Columvi. Talk to your healthcare provider about what birth control method is right for you during this time. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Columvi. are breastfeeding or plan to breastfeed. Columvi may pass into your breast milk. Do not breastfeed during treatment and for 1 month after your last dose of Columvi. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. What should I avoid while receiving Columvi? Do not drive, operate heavy machinery, or do other dangerous activities if you develop dizziness, confusion, shaking (tremors), sleepiness, or any other symptoms that impair consciousness until your signs and symptoms go away. These may be signs and symptoms of neurologic problems. These are not all the possible side effects of Columvi. Talk to your health care provider for more information about the benefits and risks of Columvi. You may report side effects to the FDA at (800) FDA-1088 or You may also report side effects to Genentech at (888) 835-2555. Please see Important Safety Information, including Serious Side Effects, as well as the Columvi full Prescribing Information and Medication Guide or visit About Genentech in hematology For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we're investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. For more information visit About Genentech Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit
