Lorenzo Falchi, Memorial Sloan Kettering Cancer Center, New York, New York, provides insights into the extended follow-up from a pivotal phase 2 study on CD20-CD3 bispecific antibody glofitamab monotherapy for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). This data was presented at the 2023 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Illinois.

Transcript:

I'm Lorenzo Falchi. I'm an assistant attending in the lymphoma service at Memorial Sloan Kettering Cancer Center in New York City. And here at ASCO, I'm presenting an extended analysis of our pivotal phase 2 trial of glofitamab for patients with relapsed or refractory diffuse large B-cell lymphoma. 

Glofitamab belongs to a class of drugs called bispecific antibodies, and it has a unique structure. It's called a 2 to 1 ratio structure. It has 1 moiety that binds to CD3 on the T-cells and 2 moieties that bind to CD20 on the target B cells. And really this study goes to address a highly unmet need, which is a highly refractory, multiply-treated diffuse large B-cell lymphoma.

In this study, 155 patients were enrolled. Glofitamab was given on a step-up dosing scheduled during cycle 1, and then given at the dose of 30 mg per cycle for 12 cycles, each lasting 3 weeks. So 9 months of therapy in total. And treatment was preceded by a pre-treatment dose of obinutuzumab to mitigate the risk of cytokine release syndrome.

Among these 155 patients, roughly a third of them had been previously exposed to CAR T-cell therapy. So this is very akin to what would we would call a real-life patient population. For this analysis, we have an extended follow-up of 21.2 months for the overall population, and for responders, which is the group of patients we focused on, that follow-up is 18.2 months. The response rates had been previously reported: an overall response rate of 52% and a complete response rate of 40%. So, very encouraging signal there.

Among the responders, which were 62 in this particular analysis, the majority of them, provided that a response was achieved, were able to retain their response within the available follow-up. Precisely 2/3 of the patients remained in response. Now, if we look at patients who were in response at the end of the treatment program, at each time point of the analysis, which is 6 months by 6 months, only a few patients really came off study due to progression. And as a result, for patients who had a complete response, for example, at cycle 3, their progression-free survival at 18 months was 72%. And for patients who had a complete response at the end of therapy, that figure rose to 80%.

Importantly, those patients who had a complete response at the end of therapy had an overall survival that was around 90%. This is a very important finding. If we think about the fact that this is a time-limited therapy, and the median follow-up is close to 2 years now, then that means that there's patients whose follow-up is close to 3, 4 years, and those patients are still alive and well and without disease and without treatment. So we're always very cautious in using the word cure, but this state looks a lot like it.

In terms of safety, we haven't really observed any new signals. The CRS rate was around 60%. The distribution of CRS was similar to what's been already reported and published. So I think this study is highly significant. It does have regulatory implications. 

We're all eagerly awaiting the outcome of those filings, and I think that glofitamab will certainly occupy a preeminent role in the treatment of patients with DLBCL that have received 2 or more lines of prior therapies, and for whom really there are very limited therapeutic options.

Source:

Falchi L, Carlo-Stella C, Morschhauser F, et al. Glofitamab monotherapy in pts with relapsed/refractory (R/R) large B-cell lymphoma (LBCL): Extended follow-up and landmark analyses from a pivotal phase II study. Presented at ASCO Annual Meeting; June 2-6, 2023; Chicago, IL. Abstract 7550.