Genentech recently announced findings from new data at the 2023 American Society of Hematology Annual Meeting and Exposition. In a presentation, data from the phase Ib/II GO40516 study of Lunsumio (mosunetuzumab-axgb), a CD20xCD3 T-cell–engaging bispecific antibody in addition to Polivy (polatuzumab vedotin-piiq), a first-in-class anti-CD79B antibody-drug conjugate in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL), were presented and concurrently published in Nature Medicine.

The new data were from a primary analysis of a phase Ib/II trial of these two agents, referred to as mosun-pola combination. The phase II component is a single arm of an ongoing multiarm trial.

The authors indicated that the primary endpoint during dose expansion was evaluated by an independent review committee (IRC), which assessed the best overall response rate, and the secondary endpoints included the investigator-evaluated overall response rate, complete response, duration of response, progression-free survival, and overall survival.

Between September 25, 2018, and February 14, 2022, 120 patients were enrolled from 15 sites in the United States and Canada, with 22 patients treated in the phase Ib dose-escalation cohort (n = 19 with R/R LBCL, n = 3 with R/R follicular lymphoma, and 98 patients treated in the phase II dose-expansion cohort [n = 98 with R/R LBCL]).

The results revealed that the primary endpoint was met during dose expansion, with IRC-assessed best overall response rate and complete response rates of 59.2% (58/98; 95% CI, 48.8-69.0) and 45.9% (45/98; 95% CI, 35.8-56.3), respectively (median follow-up, 23.9 months). The median duration of completion was not reached (95% CI: 20.5-not estimable [NE]); at 24 months average follow-up, the average progression-free survival was 11.4 months (95% CI: 6.2-18.7); and the average overall survival was 23.3 months (95% CI: 14.8-NE), highlighting the combination’s potential in the treatment of R/R LBCL. The overall safety profile was manageable in patients with R/R LBCL treated with Lunsumio plus Polivy. The authors noted that the incidence of cytokine release syndrome events was primarily low grade (grade 1: 10.2%; grade 2: 5.1%; grade 3: 3.1%).

The authors wrote, “Across dose escalation and expansion, the most common grade 3 or higher adverse events were neutropenia (25.0%, 30/120) and fatigue (6.7%, 8/120). Any-grade cytokine release syndrome occurred in 16.7% of patients.”

The authors said that results from this primary analysis from this phase Ib/II dose-escalation and dose-expansion study demonstrated that mosun-pola is an effective therapy with durable responses and a manageable safety profile in patients with R/R LBCL.

Based on their findings, the authors wrote, “In conclusion, this phase 1b/2 study demonstrated that mosun-pola, a combination regimen targeting two biologically relevant B-cell targets using a T-cell-engaging bispecific antibody and an antibody-drug conjugate, induced durable responses in patients with R/R LBCL, including patients with poor clinical and pathologic prognostic features, such as relapse after CAR-T cell therapy.”

The authors also noted that in spite of enrolling patients with poor prognostic features, the usage of this combination therapy in the outpatient setting is associated with a manageable safety profile, and based on the observed efficacy and safety profile, mosun-pola is promising as a therapy for patients with aggressive R/R LBCL ineligible for autologous stem cell transplant or aggressive intense immunochemotherapy.

Lunsumio, in combination with Polivy, is also being investigated as an outpatient therapy for patients with R/R diffuse LBCL in the ongoing phase III SUNMO study [NCT05171647].

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