Genentech presents data on glofitamab, mosunetuzumab potential at ASH 2022

Genentech announced that updated clinical data for its CD20xCD3 T-cell engaging bispecific antibodies, including five oral presentations, were presented at the 64th American Society of Hematology Annual Meeting & Exposition, December 10-13, 2022. Updated results for the investigational bispecific glofitamab in people with relapsed or refractory large B-cell lymphoma suggest glofitamab has the potential to be the first off-the-shelf CD20xCD3 T-cell engaging bispecific antibody that can be given for a fixed period of time to people with heavily pretreated aggressive lymphoma. These data will be presented at the meeting and simultaneously published online in the New England Journal of Medicine. Additionally, updated data for mosunetuzumab continued to demonstrate clinically meaningful outcomes in people with heavily pretreated follicular lymphoma. Mosunetuzumab is a fixed-duration treatment that can be administered in the outpatient setting, which could allow people the possibility of experiencing a lasting remission with a treatment-free period. Pivotal Phase II Glofitamab Data Presented at ASH 2022 and Published in NEJM: Updated data from the pivotal Phase II NP30179 study in people with R/R LBCL showed glofitamab given as a fixed course induced early and durable responses that were maintained beyond the end of treatment. Most patients who had achieved a complete response at the end of treatment experienced durable responses, with a median CR follow-up from end of treatment of 11.5 months. Twelve months after the end of treatment with glofitamab, 61% of patients maintained a CR, 92.6% remained progression-free, and only one patient experienced disease progression. Simultaneously, an earlier data cut from the Phase II NP30179 study in R/R diffuse large B-cell lymphoma was published online in NEJM. Data from this pivotal Phase II study have been submitted for review to the European Medicines Agency, and submissions to additional health authorities worldwide, including the U.S. Food and Drug Administration, are ongoing. Updated Pivotal Phase II Mosunetuzumab Data Presented at ASH 2022: An updated analysis from the pivotal Phase II GO29781 study of mosunetuzumab in people with R/R FL who had received two or more prior therapies showed 60.0% achieved a CR and 77.8% achieved an objective response at a median follow-up of 28.3 months. After 24 months of achieving a CR, 62.7% of patients remained in remission. Overall, 48.3% of patients remained progression-free. The median duration of response, median duration of CR, and median progression-free survival were not reached. Safety was consistent with the previous analysis of study data, with no new cytokine release syndrome events or Grade 3 or higher adverse events reported. CRS events were experienced by 44% of patients and were predominately low grade and during cycle one. Additional Mosunetuzumab and Glofitamab Data Presented at ASH 2022: Genentech continues to evaluate mosunetuzumab and glofitamab as part of its commitment to providing off-the-shelf therapies for people with lymphomas that can meet their diverse needs, including fixed-duration treatment options. Additional data presented at ASH 2022 include the following: A subcutaneous formulation of mosunetuzumab demonstrated comparable efficacy with the intravenous formulation and a manageable safety profile in people with R/R non-Hodgkin’s lymphoma. The most common AEs were injection site reactions and CRS events, which were all Grade 1 or 2. These findings suggest that a SC formulation of mosunetuzumab may offer patients a treatment option that could reduce their time spent in treatment centers. Updated results from the Phase I/II G050554 study of mosunetuzumab monotherapy in elderly/unfit patients with previously untreated DLBCL and additional analyses from the Phase I/II G040516 study of mosunetuzumab in combination with Polivy in heavily pretreated people with DLBCL continued to show promising efficacy and manageable safety, highlighting the potential of mosunetuzumab in these patient populations.Results from the Phase I/II NP30179 study evaluating glofitamab as a monotherapy following pretreatment with obinutuzumab in patients with heavily pretreated R/R mantle cell lymphoma continued to show early, high and durable response rates in this difficult-to-treat disease. After a median follow-up of eight months, the overall response rate was 83.8%, with the majority of patients showing durable complete responses at the data cut off. The most common AE was CRS, with the majority low grade. Data from the safety and expansion cohorts of the Phase Ib NP40126 study evaluating glofitamab in combination with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone in patients with previously untreated DLBCL showed, after a median follow-up of 8.5 months, a best ORR of 92.7% and a complete metabolic response rate of 72.7%. In the safety cohort, CRS events were all low grade, and serious AEs were reported in 18 patients. Both mosunetuzumab and glofitamab are being investigated as SC formulations and in Phase III studies that will expand the understanding of their impact in earlier lines of treatment, with the aim of continuing to address the diverse needs and preferences of people with blood cancers. This includes the confirmatory Phase III CELESTIMO study investigating mosunetuzumab plus lenalidomide as a chemotherapy-free option for patients with R/R FL; the Phase III SUNMO study investigating mosunetuzumab plus Polivy versus rituximab in combination with gemcitabine plus oxaliplatin in patients with R/R aggressive B-cell NHL who are ineligible for autologous stem cell transplant; and the Phase III STARGLO study evaluating glofitamab in combination with gemcitabine and oxaliplatin versus rituximab in combination with GemOx in patients with R/R DLBCL who are ineligible for ASCT.