ICML 2025 | Extended follow-up results from the MITHIC-FL1 trial: subcutaneous mosunetuzumab for advanced FL

This year at the Lugano meeting we thought we’d present an extended follow-up of our multi-center Phase II study of subcutaneous mosunetuzumab for the treatment of advanced follicular lymphoma named the MITHIC-FL1 study. This study was initiated in 2022 but now we have relatively mature results and really the idea behind it is that standard of care chemoimmunotherapy which remains a standard of care for follicular lymphoma is insufficient in several ways including not being a curative option and carrying several toxicities including infectious disease and complications and secondary cancers. The pathobiology of follicular lymphoma is such that redirecting the dysfunctional T-cells that are in the intratumoral space may be irrational and at the same time effective therapies. So CD20xCD3 bispecific antibodies really represent a very rational pathogenetic therapy for this disease. MITHIC-FL1 was a Phase II study that included 78 safety evaluable patients and 76 efficacy evaluable patients. These patients were all CD20 positive follicular lymphoma, grade one to three A, in need of therapy for the GELF criteria. And the primary endpoint of the study was complete response. This was a treatment that was given subcutaneously, entirely on an outpatient basis, using a step-up dosing in cycle one. And then depending on the response after eight cycles or six months of therapy, patients would discontinue treatment if they were in a CR complete response continue up to another six months if they were in a partial response or come off study if the response was unsatisfactory. But we were very reassured to see that the primary endpoint of the study was met. The complete metabolic response rate at the end of therapy was 82% and the overall objective response rate was 95%. These figures were preserved across key subgroups including patients with higher-risk disease such as high SUV or lymphoma follicular lymphoma grade 3a or high burden of disease and also across groups defined cytogenetically or molecularly with the use of FISH testing or next-generation sequencing so we really couldn’t identify a subgroup of patients that didn’t benefit from this treatment we also didn’t see any new safety signals. CRS remains low grade mostly. We saw it in 54% of patients. Only two had a grade two event. The rest of them was grade one. Injection site reactions, skin manifestations, infectious complications were the other common adverse events, but really nothing new compared to the last time we analyzed the data. So that was reassuring to us. So I think comprehensively, the collection of the data we put together continues to support studying subcutaneous mosunetuzumab as a frontline therapy for high-burden follicular lymphoma. And there’s other studies in this space that are, I think, corroborating our findings as well. So it’s hopefully the start of a bright new era.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.