Genentech announced today that the U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) has discussed the supplemental Biologics License Application (sBLA) for Columvi® (glofitamab-gxbm) in combination with gemcitabine and oxaliplatin (GemOx) for the treatment of people with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are not candidates for autologous stem cell transplant (ASCT).
The committee's discussion focused on the applicability of the Phase III STARGLO study results to the U.S. patient population, with some committee members indicating that further data may be needed. The FDA's final decision on the application is expected by July 20, 2025.
Significant Survival Benefit Demonstrated in STARGLO Study
The STARGLO study, a multicenter, open-label, randomized clinical trial, showed that Columvi in combination with GemOx reduced the risk of death by 41% (hazard ratio [HR]=0.59, 95% CI: 0.40–0.89, p=0.011) compared to rituximab plus GemOx (R-GemOx) in patients with R/R DLBCL who are not candidates for ASCT.
The Columvi combination also demonstrated a 63% reduction in the risk of disease progression or death (progression-free survival, PFS) compared to R-GemOx (HR=0.37; 95% CI: 0.25–0.55, p<0.0001).
A follow-up analysis with a median follow-up of 20.7 months showed continued benefit, with median overall survival for patients treated with the Columvi combination reaching 25.5 months—nearly double the 12.9 months observed in the R-GemOx arm (HR=0.62, 95% CI: 0.43-0.88).
"Columvi in combination with GemOx demonstrated a 41% reduction in risk of death in a Phase III, randomized, multiregional clinical trial, supporting its recent approval by the European Commission and inclusion in the U.S. National Comprehensive Cancer Network treatment guidelines as a category 1 preferred regimen," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development at Genentech.
Safety Profile and Treatment Duration
The safety profile of the Columvi combination appeared 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), primarily due to disease progression in the R-GemOx arm.
One of the most common adverse events was cytokine release syndrome (CRS), which was generally low grade (Any Grade: 44.2%, Grade 1: 31.4%, Grade 2: 10.5%, Grade 3: 2.3%) and occurred primarily in Cycle 1.
Global Study with Potential U.S. Relevance
The STARGLO study enrolled 274 patients globally across 62 sites in 13 countries, including the U.S., Australia, and multiple European countries, with the majority of patients (52%) enrolling outside of Asia.
Genentech maintains that the clinical and disease characteristics of the overall population enrolled in this multiregional clinical trial are representative of U.S. patients with DLBCL.
"Many of the patients with DLBCL who I see in my clinic are similar to the patients reflected in this study, making the glofitamab-GemOx regimen an important potential treatment option," said Krish Patel, M.D., Director of Lymphoma Research, Sarah Cannon Research Institute. "These patients need more effective, readily available treatment options and the compelling results from STARGLO deliver on this need."
Addressing an Urgent Unmet Need
For people with R/R DLBCL, therapy options that can provide durable remissions are limited. In the U.S., approximately 75% of patients with R/R DLBCL are not candidates for, cannot tolerate, or do not have access to the latest treatments.
New treatments that can be initiated in community practices, where the majority of patients are treated, and have the potential to provide rapid disease control with durable remissions, could meaningfully address the needs of patients with this aggressive and life-threatening form of lymphoma.
Regulatory Status
Based on the STARGLO data, this Columvi combination is already approved in more than 30 countries, including the European Union, for people with R/R DLBCL who are ineligible for ASCT.
Columvi in combination with GemOx was recently 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, including the U.S. The STARGLO study is intended as a confirmatory study to convert the accelerated approval of Columvi in the U.S. to full approval.
About Columvi
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. It was designed with a novel 2:1 structural format that brings T cells in close proximity to B cells, activating the release of cancer cell-killing proteins from the T cell.
The drug is part of Genentech's broad CD20xCD3 T-cell-engaging bispecific antibody clinical development program, which aims to provide tailored treatment options for people with blood cancers. Genentech is investigating Columvi as a monotherapy and in combination with other medicines for the treatment of DLBCL and mantle cell lymphoma.
About 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.
While DLBCL 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.
The FDA's evaluation of this Columvi combination for R/R DLBCL is ongoing, with a decision on approval expected by July 20, 2025. Two-year follow-up data from STARGLO will be presented at the upcoming 61st American Society of Clinical Oncology (ASCO) Annual Meeting from May 30 - June 3, 2025.
