FDA Delivers a CRL to Glofitamab for Relapsed/Refractory DLBCL

Additional reporting by Laura Joszt, MA.

The FDA has issued a complete response letter (CRL) to the combination of glofitamab-gxbm (Columvi; Genentech) plus gemcitabine and oxaliplatin (GemOx) for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in patients who are not candidates for autologous stem cell transplant (ASCT) and have failed on at least 1 prior line of therapy.¹

According to the CRL, the data from the global, open-label phase 3 STARGLO study (NCT04408638) were not sufficient to support approval in the second-line indication. The STARGLO trial had also been intended as a postmarketing confirmatory study to cover the accelerated approval of glofitamab in the third line or later to treat DLBCL.²

"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,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, said in a statement.¹ “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.”

The FDA's Oncologic Drugs Advisory Committee had voted 8 to 1 against the applicability of the STARGLO trial results for glofitamab plus chemotherapy for US patients with relapsed or refractory DLBCL.³

STARGLO Results

In this ongoing trial, adult patients (18 years and older) have been randomized to receive either glofitamab plus gemcitabine and oxaliplatin or rituximab plus gemcitabine and oxaliplatin.⁴ Patients in the glofitamab arm received the intravenous (IV) treatment combination for up to 8 cycles, followed by 4 cycles of glofitamab monotherapy, with gemcitabine preceding oxaliplatin; their pretreatment is intravenous obinutuzumab 7 days prior to their first dose of glofitamab. Participants in the rituximab arm received IV rituximab on day 1 of each cycle, again for up to 8 cycles, also with gemcitabine preceding oxaliplatin. In both arms, treatment is administered in 21-day cycles.

Overall survival out to a maximum of 5 years is the primary outcome of interest, and secondary measures include progression-free survival, objective response rate, duration of complete response, and time to deterioration in lymphoma symptoms—all up to a max period of 5 years.

Glofitamab plus gemcitabine and oxaliplatin received a complete response letter.

Image Credit: wladimir1804 - stock.adobe.com

The average age for a DLBCL diagnosis—this being the most common form of non-Hodgkin lymphoma—is mid-60s, and it is considered an aggressive form of leukemia.⁵ In addition to age, comorbidities are implicated in disqualifying patients from ASCT, resulting in treatment barriers that impede survival outcomes. There is a great need among this patient population for alternative treatment options, especially with standard second-line treatment typically encompassing high-dose chemotherapy followed by a stem-cell transplant.

"For patients with this aggressive form of lymphoma, effective treatment after relapse is paramount," Jeremy Abramson, MD, director of the Jon and Jo Ann Hagler Center for Lymphoma at the Massachusetts General Hospital Cancer Center, and principal investigator of the STARGLO study, said in a statement.¹ "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."

References

1. Genentech provides update on supplemental biologics license application for Columvi combination for people with relapsed or refractory diffuse large B-cell lymphoma. News release. Genentech. July 18, 2025. Accessed July 18, 2025. https://www.gene.com/media/press-releases/15070/2025-07-18/genentech-provides-update-on-supplementa
2. Joszt L. FDA approves glofitamab-gxbm to treat adults with relapsed/refractory DLBCL. AJMC^®. June 16, 2023. Accessed July 18, 2025. https://www.ajmc.com/view/fda-approves-glofitamab-gxbm-to-treat-adults-with-relapsed-refractory-dlbcl
3. Ryan C. FDA ODAC votes against the applicability of STARLGLO data for glofitamab plus chemo for U.S. patients with R/R DLBCL. OncLive^®. May 20, 2025. Accessed July 18, 2025. https://www.onclive.com/view/fda-odac-votes-against-the-applicability-of-starglo-data-for-glofitamab-plus-chemo-for-u-s-patients-with-r-r-dlbcl
4. A phase III study evaluating glofitamab in combination with gemcitabine + oxaliplatin vs rituximab in combination with gemcitabine + oxaliplatin in participants with relapsed/refractory diffuse large B-cell lymphoma. ClinicalTrials.gov. Updated April 13, 2025. Accessed June 19, 2025. https://clinicaltrials.gov/study/NCT04408638
5. Diffuse large B cell lymphoma. Cancer Support Community/Gilda’s Club. Accessed June 19, 2025. https://www.cancersupportcommunity.org/diffuse-large-b-cell-lymphoma-dlbcl