Glofitamab Plus Chemotherapy Meets OS End Point in R/R DLBCL

Treatment with glofitamab-gxbm (Columvi) in combination with gemcitabine and oxaliplatin led to a statistically significant improvement in overall survival (OS) vs rituximab (Rituxan) in combination with gemcitabine and oxaliplatin in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who had received at least 1 prior line of therapy and were not eligible for autologous stem cell transplant (ASCT), meeting the primary end point of the phase 3 STARGLO study (NCT04408638).¹

Furthermore, safety data with the study combination were consistent with the known safety profiles of these agents. Genentech plans to share these data with health authorities and present the information at an upcoming medical meeting.¹

“[Patients] with this aggressive lymphoma facing relapse or progression after initial treatment have limited options—particularly those who are ineligible for stem cell transplant,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, stated in a press release. “Building on [glofitamab’s] established benefits, these data demonstrate the potential of this combination regimen to improve survival outcomes in earlier lines of treatment.”

The multicenter, open-label, randomized STARGLO trial assessed the safety and efficacy of glofitamab in combination with gemcitabine and oxaliplatin compared with rituximab plus gemcitabine and oxaliplatin in patients with DLBCL. Outcome measures of this trial include a primary end point of OS, as well as secondary end points of progression-free survival, objective response rate (ORR), complete response rate, duration of ORR, and safety and tolerability.¹

Patients were required to have histologically diagnosed relapsed/refractory DLBCL, as well as exposure to at least 1 prior systemic therapy, except for patients who were eligible for high-dose chemotherapy followed by ASCT, per the study protocol. Tumor tissue availability; measurable lesions; an ECOG performance status of 0 to 2; and adequate hematologic and renal function were also among the required enrollment criteria.²

Exclusion criteria encompassed various factors, such as candidacy for stem cell transplantation after progression on only 1 prior therapy; specific lymphoma subtypes; prior allergic reactions to certain antibodies; contraindications to investigation-specific medications; prior treatment with certain agents, including bispecific antibodies targeting CD20 and CD3; peripheral neuropathy assessment; and recent treatments for cancer.

Patients were randomly assigned 2:1 to receive glofitamab plus chemotherapy or rituximab plus chemotherapy for up to 8 21-day cycles. Patients in the glofitamab arm received glofitamab plus chemotherapy, followed by up to 4 cycles of glofitamab monotherapy and a single dose of obinutuzumab (Gazyva) administered 7 days prior to the first dose of glofitamab.

Glofitamab, an off-the-shelf CD20xCD3 T-cell engaging bispecific antibody, uses a novel 2:1 structural format, which targets CD3 on T cells and CD20 on B cells, inducing T-cell release of cancer cell–killing proteins upon close interaction with B cells.¹ The agent is also a fixed-duration bispecific antibody and was the first fixed-duration bispecific antibody to receive accelerated approval from the FDA, as well as conditional marketing authorization from the European Commission, for the treatment of patients with relapsed/refractory DLBCL following 2 or more lines of systemic therapy.^3,4

Notably, these regulatory decisions by both the FDA and European Commission were based on data from the phase 1/2 NP30179 trial (NCT03075696), which demonstrated an ORR of 56% (95% CI, 47%-65%) and a CR rate of 43% (95% CI, 35%-52%).^3,4

References

1. Genentech’s Columvi meets primary endpoint of overall survival in people with relapsed or refractory diffuse large B-cell lymphoma in phase III STARGLO study. News release. Genentech. April 14, 2024. Accessed April 15, 2024. https://www.gene.com/media/press-releases/15021/2024-04-14/genentechs-columvi-meets-primary-endpoin
2. 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 8, 2024. Accessed April 15, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT04408638
3. FDA approves Genentech’s Columvi, the first and only bispecific antibody with a fixed-duration treatment for people with relapsed or refractory diffuse large B-cell lymphoma. News release. Genentech. June 15, 2023. Accessed April 15, 2024. https://www.gene.com/media/press-releases/14994/2023-06-15/fda-approves-genentechs-columvi-the-firs
4. European Commission approves Roche’s fixed-duration Columvi (glofitamab) for people with relapsed or refractory diffuse large B-cell lymphoma. News release. Roche. July 11, 2023. Accessed April 15, 2024. https://www.roche.com/media/releases/med-cor-2023-07-11