FDA Denies Glofitamab Plus Chemo Approval for Relapsed DLBCL

The U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding the supplemental biologics license application (sBLA) for the use of glofitamab-gxbm (Columvi) in conjunction with chemotherapy for treating patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). This decision was announced on July 18, 2025, following a review of data from the STARGLO trial, which did not provide sufficient evidence to support approval within the U.S. patient population.

The STARGLO trial (NCT04408638) aimed to confirm the efficacy of glofitamab combined with gemcitabine and oxaliplatin (GemOx) in patients who had already undergone at least one line of therapy and were ineligible for autologous stem cell transplantation (ASCT). While the study indicated encouraging overall response rates (ORR) and overall survival (OS) outcomes, safety concerns emerged, including a higher incidence of adverse events compared to the traditional treatment with rituximab (Rituxan) in combination with GemOx.

In a prior advisory committee meeting held in May 2025, the FDA's Oncologic Drugs Advisory Committee voted overwhelmingly (8 to 1) against the applicability of STARGLO trial results to the broader U.S. population. This decision has caused disappointment among stakeholders, particularly Genentech, the manufacturer of glofitamab. Genentech's Chief Medical Officer, Dr. Levi Garraway, expressed confidence in the drug's potential, stating, "While we are disappointed with this outcome, we remain confident in the data supporting the value of glofitamab for U.S. patients who have relapsed following initial treatment."

Glofitamab previously received accelerated approval in June 2023 for patients with relapsed/refractory DLBCL not otherwise specified or arising from follicular lymphoma after two or more prior lines of systemic therapy. This earlier approval remains intact, and Genentech is now exploring other treatment settings for glofitamab, including its combination with polatuzumab vedotin-piiq (Polivy) in the forthcoming SKYGLO trial (NCT06047080).

The STARGLO study's findings, presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, reported an ORR of 68.3% for glofitamab compared to 40.7% for rituximab plus GemOx. The complete response rates were also markedly higher, with 58.5% of patients in the glofitamab arm achieving a complete response against 25.3% in the rituximab group. Furthermore, the median OS for patients treated with glofitamab was not evaluable compared to 13.5 months for those receiving rituximab.

Safety data from the trial indicated a concerning trend; grade 3 or higher adverse events occurred in 76.7% of the glofitamab cohort versus 40.9% in the rituximab group. Serious adverse events were also more frequent, highlighting the need for ongoing monitoring and evaluation before potential approval.

As Genentech seeks to re-engage the FDA with new data from the SKYGLO trial, the company remains committed to expanding treatment options for patients suffering from this aggressive form of lymphoma. The implications of the FDA's decision resonate throughout the oncology community, emphasizing the critical balance between innovative therapies and patient safety. The ongoing dialogue between Genentech and the FDA will be pivotal in determining the future of glofitamab in lymphoma treatment protocols.