Roche Showcases New Clinical Data on CD20xCD3 T-Cell Engaging Bispecific Antibodies for NHL Immunotherapy at ASCO 2021

Compiled and Translated by | River

Recently, according to foreign media reports, Roche's Genentech presented new data at the 2021 ASCO Annual Meeting on its investigational CD20xCD3 T-cell-engaging bispecific antibodies mosunetuzumab and glofitamab, as well as its first CD79b-targeting antibody-drug conjugate Polivy (polatuzumab vedotin), demonstrating enhanced clinical benefit for patients with non-Hodgkin lymphoma (NHL).

Approximately 500,000 individuals worldwide are diagnosed with NHL annually; however, current treatment options remain limited, and resistance to existing therapies or relapse following treatment is common. The most common form of NHL is an aggressive subtype, diffuse large B-cell lymphoma (DLBCL), which accounts for approximately 40% of newly diagnosed NHL cases. Without treatment, life expectancy is typically measured in weeks to months. In clinical trials to date, the investigational CD20xCD3 T-cell-engaging bispecific antibodies mosunetuzumab and glofitamab have demonstrated promising responses across various NHL subtypes, including relapsed or refractory (R/R) DLBCL and follicular lymphoma (FL).

Key data presented for mosunetuzumab and glofitamab include:

• The Phase I NP30179 study investigated glofitamab dose escalation in heavily pretreated patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL), demonstrating a sustained complete response (CR) and an acceptable safety profile. After a median follow-up of 6.3 months, results showed that in patients with aggressive (fast-growing) NHL, glofitamab achieved a complete metabolic response rate of 71.4% (defined as the disappearance of metabolic tumor activity). The most common adverse events (AEs) were cytokine release syndrome (CRS) (63.5%), neutropenia (38.5%), and pyrexia (32.7%); CRS events were predominantly low-grade and primarily limited to the first treatment cycle.
• The Phase I/II GO40516 study evaluating mosunetuzumab in combination with Polivy for R/R NHL demonstrated favorable efficacy and an acceptable safety profile. This regimen achieved a 54.5% CR rate in all patients. Of the evaluated patients, 86% had aggressive NHL, with a CR rate of 47.4% in this subgroup. The most common treatment-related AEs were neutropenia (45.4%), fatigue, nausea, and diarrhea (all 36.4%), and CRS (9.1%; all Grade 1).

Extensive development programs for mosunetuzumab and glofitamab are also ongoing, including:

• The Phase III GO42909 study evaluating the efficacy of mosunetuzumab + lenalidomide versus Rituxan (rituximab) + lenalidomide in R/R FL will begin patient enrollment shortly.
• The Phase III GO41944 open-label randomized trial of glofitamab is also ongoing, which aims to evaluate the safety and efficacy of glofitamab + gemcitabine + oxaliplatin (glofit-GemOx) versus Rituxan + GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).

The CD79b-targeted antibody-drug conjugate Polivy is already a treatment option for patients with R/R DLBCL and continues to demonstrate potential across various combination regimens. The key data presented include:

• Results from the Phase Ib/II GO29834 study demonstrated promising activity for the novel triplet combination of Polivy, Rituxan, and lenalidomide in difficult-to-treat R/R DLBCL. With a median follow-up of 9.7 months, the median overall survival for patients treated with the triplet therapy was 10.9 months (95% CI: 7.4–NE), and the median progression-free survival was 6.3 months (95% CI: 4.5–9.7). The most frequently reported Grade 3–4 adverse events were neutropenia (58.0%), thrombocytopenia (14.0%), infections (14.0%), and anemia (11.0%).

Genentech aims to submit the regulatory filing for mosunetuzumab by the end of 2021, following its Breakthrough Therapy designation from the FDA in June 2020.

Source: Genentech Presents Latest Advances With Immunotherapies in Non-Hodgkin’s Lymphoma