SHERIDAN, WYOMING – July 25, 2025 – Genentech, a member of the Roche Group, announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for its supplemental Biologics License Application (sBLA) for Columvi® (glofitamab-gxbm) in combination with gemcitabine and oxaliplatin (GemOx). The application sought approval for this regimen as a second-line treatment for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem cell transplant.
FDA Response Highlights Evidence Requirements for Earlier-Line Indications
According to the FDA, data from the STARGLO study did not provide sufficient evidence to support the proposed indication in the second-line U.S. setting. As a result, Columvi retains its current accelerated approval for use in third-line or later DLBCL. Genentech is continuing discussions with the agency to designate the ongoing Phase III SKYGLO trial—investigating Columvi in combination with Polivy®, Rituxan®, and chemotherapy—as the new postmarketing requirement for full approval.
“While we are disappointed with this outcome, we remain confident in the data supporting the value of Columvi for U.S. patients who have relapsed following initial treatment, and its key role as monotherapy in the third-line setting,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We are committed to bringing Columvi to more people living with lymphoma and are actively exploring its potential in additional treatment settings, including as frontline therapy.”
Global Endorsements Emphasize Columvi’s Impact
Despite the FDA’s CRL, Columvi-GemOx is already approved in over 35 countries worldwide, including the EU, and is recommended in clinical practice guidelines such as those from the U.S. National Comprehensive Cancer Network (NCCN). The STARGLO trial demonstrated a 41% reduction in the risk of death compared to GemOx alone (HR=0.59; 95% CI: 0.40–0.89; p=0.011), with results published in The Lancet and reinforced by two-year follow-up data presented at the 2025 ASCO Annual Meeting.
“For patients with this aggressive form of lymphoma, effective treatment after relapse is paramount. The STARGLO study showed that Columvi-GemOx significantly improves overall survival and could have a positive impact for patients earlier in their treatment journey. This regimen is already approved in over 35 countries, which underscores the urgent need it addresses,” said Jeremy Abramson, M.D., director, Jon and Jo Ann Hagler Center for Lymphoma at the Massachusetts General Hospital Cancer Center, and principal investigator of the STARGLO study.
Strategic Focus on Frontline Innovation
Genentech is shifting strategic focus toward the Phase III SKYGLO trial, which evaluates Columvi in combination with Polivy and standard chemotherapy for previously untreated large B-cell lymphoma. The company views early-line treatment as critical to improving long-term outcomes and reducing relapse rates in DLBCL, where up to 40% of patients experience disease progression after initial therapy.
Advancing T-Cell Engagers and ADC Combinations in Hematology
Columvi is part of Genentech’s expanding CD20xCD3 bispecific antibody platform, which aims to activate T cells to destroy malignant B cells with precision. Its dual-binding 2:1 format allows engagement of CD3 on T cells and CD20 on B cells, initiating targeted immune responses. Genentech is exploring Columvi in both monotherapy and combination regimens for multiple lymphoma subtypes.
Polivy, a CD79b-directed antibody-drug conjugate, complements this strategy by delivering cytotoxic agents directly to malignant B cells while minimizing effects on healthy cells. The integration of these novel mechanisms of action positions Genentech at the forefront of hematologic cancer innovation.
Continued Regulatory Efforts and Global Expansion
While the CRL represents a regulatory setback in the U.S., Genentech continues submitting Columvi-GemOx data to additional health authorities worldwide. The company remains committed to working with regulators to broaden access to therapies that address high unmet needs in relapsed and refractory DLBCL.
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