Methods and Design of Phase 1/2 Glofitamab Study in LBCL

Cyrus M. Khan, MD, hematologist in the Division of Hematology and Cellular Therapy at West Penn Hospital of Allegheny Health Network, discusses the phase 1/2 trial (NCT03075696) of glofitamab (Columvi) for use as a treatment option for patients with relapsed/refractory large B-cell lymphoma.

Glofitamab is a CD20/CD3 T-cell-engaging bispecific monoclonal antibody being investigated in a multicenter, open-label, phase 1/2 study as a single agent or in combination with obinatuzumab (Gazyva) for this patient population. In the phase 2 portion of the study, patients with relapsed or refractory diffuse large B-cell lumphoma who had received at least 2 prior lines of therapy were enrolled and given pretreatment with obinutuzumab to mitigate cytokine release syndrome, followed by fixed-duration glofitamab monotherapy for a total of 12 cycles.

Investigators assessed the primary end point of complete response according to assessment by an independent review committee, and the key secondary end points of duration of response, survival, and safety.

Transcription:

0:10 | This was a phase 2 clinical trial, and it took patients with relapsed/refractory large B-cell lymphoma, whether they had transformed lymphomas or hybrid B-cell lymphomas. They took all comers, whether they were post-autologous transplant [or other]. Initially, the idea was to give them 1 dose of obinutuzumab to minimize the cytokine release syndrome, because all these products do cause cytokine release syndrome.

0:38 | Then there was a step-up dosing involved. It started off at a very small dose and eventually the dose was taken up to the highest dose that was tolerable. The infusion is given every 3 weeks, and just for 12 cycles. The idea is to get a finite duration of treatment instead of something that would continue indefinitely for those patients. That was pretty much the design of the trial and of course, assessments were done after 3 cycles, and most of the patients who achieved the response, got the response at that third cycle.