Columvi Combo at FDA

Roche announced that an FDA Oncologic Drugs Advisory Committee (ODAC) discussed the supplemental Biologics License Application (sBLA) for Columvi (glofitamab) 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 discussion focussed on the applicability of the phase III STARGLO results to the US patient population, with Committee members citing that further data are needed. The STARGLO study was a multiregional clinical trial (MRCT) that enrolled 274 patients globally across 62 sites in 13 countries, including the US, Australia, and multiple European countries, with the majority of patients (52%) enrolling outside of Asia.

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.

The clinical and disease characteristics of the overall population enrolled in this multiregional clinical trial are representative of US patients with this disease today. On that basis the STARGLO results are applicable to US patients. Based on extensive guidelines and real-world clinical practice, there are no biological or clinical differences for DLBCL management worldwide. There is a broad and robust clinical development programme of Columvi, indicating that region and/or race are not relevant determinants of outcomes to treatment.

A statistically significant 41% reduction in the risk of death (hazard ratio [HR]=0.59, 95% confidence interval [CI]: 0.40–0.89, p=0.011) was observed in patients treated with Columvi in combination with GemOx versus MabThera/Rituxan (rituximab) plus GemOx (R-GemOx). The Columvi combination also met its key secondary endpoints, with a 63% reduction in risk of disease worsening or death (progression-free survival, PFS) compared to R-GemOx (HR=0.37; 95% CI: 0.25–0.55, p<0.0001).  Median OS was 25.5 months for people treated with the Columvi combination, nearly double what was seen for people treated with R-GemOx at 12.9 months (HR=0.62, 95% CI: 0.43-0.88) in a follow-up analysis. Safety of the combination 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 four), 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 (Any Grade: 44.2%, Grade 1: 31.4%, Grade 2: 10.5%, Grade 3: 2.3%) and occurred primarily in Cycle 1. Two-year follow-up data from STARGLO will be presented at the upcoming 61st American Society of Clinical Oncology (ASCO) Annual Meeting from 30 May - 3 June 2025.

Based on the STARGLO data, this Columvi combination is approved in more than 30 countries, including the EU, 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 US. STARGLO is intended as a confirmatory study to convert the accelerated approval of Columvi in the US to full approval.

“Columvi in combination with GemOx demonstrated a 41% reduction in risk of death in a phase III, randomised, multiregional clinical trial, supporting its recent approval by the European Commission and inclusion in the US National Comprehensive Cancer Network treatment guidelines as a category 1 preferred regimen,” said Dr. Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development. “We believe the STARGLO results are applicable to US patients, with the global study population closely mirroring the real-world clinical profile of DLBCL patients in the US, and we will continue working with the FDA on the regulatory path forward.”

“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 Dr. Krish Patel, 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

See citations- Abramson J et al. Glofitamab plus Gemcitabine and Oxaliplatin (Glofit-GemOx) for Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL): Results of a Global Randomized Phase III trial (STARGLO). Presented at: EHA Hybrid Congress; 2024 Jun 3-16. Abstract #LB3438.

Abramson J et al. Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for relapsed or refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomised, open-label trial. Lancet 2024; 404: 1940