Efficacy and safety results of a first-in-class PD-1/IL-2 ^α-bias bispecific antibody fusion protein IBI363 in patients (pts) with immunotherapy-treated, advanced acral and mucosal melanoma.

Abstract

2502 Background: Despite great success of immunotherapy (IO) in advanced melanoma, there remains an unmet clinical need for resistant tumors. Pts with acral and mucosal melanomas show limited benefit from current therapies. IBI363, a first-in-class PD-1/IL-2 α-bias bispecific antibody fusion protein that blocks PD-1 and activates α-bias IL-2 to rejuvenate exhausted tumor-specific T cells, has shown encouraging efficacy in pts with advanced melanoma. Here, we present results of IBI363 from a phase 1 study (NCT05460767) and a phase 2 study (NCT06081920) of pts with IO-treated, advanced acral and mucosal melanoma. Methods: Eligible pts with IO-treated advanced acral and mucosal melanoma were enrolled. IBI363 was administered intravenously at 0.1 mg/kg every week, 0.3/0.6/1 mg/kg every 2 weeks (Q2W), or 1/1.5/2/3 mg/kg every 3 weeks (Q3W). Primary endpoints for the phase 1 study were dose-limiting toxicity (DLT) and safety, and for the phase 2 study were safety and investigator-assessed objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and progression-free survival (PFS) according to RECIST v1.1. Results: As of December 6, 2024, 91 pts were enrolled across the phase 1 (n = 76) and phase 2 (n = 15) studies (male: 47%; median age: 57 years; Asian: 100%; ECOG PS 1: 66%; stage IV: 89%); 47 pts had acral melanoma and 44 had mucosal melanoma. Median follow-up time was 8.2 months. Median treatment duration was 13.4 weeks (range: 2.0-72.4). Treatment-emergent adverse events (TEAEs) occurred in 90/91 (98.9%) pts including 27 (29.7%) pts with grade ≥3 (≥G3) TEAEs. TEAEs led to treatment discontinuation in 3 (3.3%) pts, and 1 (1.1%) pt had a TEAE leading to death which was considered to be treatment-related (sepsis). Most common TEAEs were arthralgia (59.3%, with 4.4% ≥G3), rash (42.9%, with 3.3% ≥G3), and anemia (42.9%, with 2.2% ≥G3). Among all pts with at least one post-baseline tumor assessment (n = 87), 1 pt had a complete response, 22 had partial responses, 33 had stable disease, 31 had progressive disease. ORR was 26.4% (95%CI: 17.6-37.0) with 16 responses confirmed and 2 pts still waiting for confirmation; DCR was 64.4% (95%CI: 53.4-74.4). Among pts treated at 1mg/kg and above (n = 74), the ORR was 28.4% (95%CI: 18.5-40.1) and DCR was 68.9% (95%CI: 57.1-79.2). Patients treated at 1 mg/kg Q2W (n = 30) had median DOR 14.0 months with a median follow-up of 9.1 months and 50.0% events; the median PFS was 5.7 (95% CI, 3.6-6.7) months with a median follow-up of 11.0 months and 73.3% events. Conclusions: IBI363 showed encouraging efficacy in pts with IO-treated advanced acral and mucosal melanoma. The safety profile was acceptable and manageable. Further global clinical development of IBI363 in melanoma is ongoing. Clinical trial information: NCT05460767 and NCT06081920 .