Background IBI363 was designed to simultaneously block the PD-1/PD-L1 pathway and activate the IL-2 pathway with improved efficacy and reduced toxicity. In previously reported phase 1 results, IBI363 was well tolerated with promising efficacy in advanced melanoma. Herein, we present the analysis of IBI363 in IO-naïve melanoma patients (defined as no previous exposure to immune checkpoint inhibitors) from the phase 1 study (NCT05460767) and an additional cohort from a phase 2 study (NCT06081920).

Methods Eligible IO-naïve patients with unresectable locally advanced or metastatic melanoma were enrolled. IBI363 monotherapy was administered intravenously at 0.3 mg/kg QW, 0.6 mg/kg Q2W, 1 mg/kg Q2W, 1.5 mg/kg Q3W or 3 mg/kg 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 Aug 19^th, 2024, a total of 40 patients were enrolled (males: 50.0%; median age: 61.0 years; ECOG PS 1: 62.5%; stage IV: 77.5%; prior systemic anti-tumor medication: 47.5%). Melanoma subtypes included mucosal (n=26), acral (n=4), cutaneous (n=7) and unknown primary site(n=3). Median treatment duration was 10 weeks (range: 3.0–51.6), with 27 patients (67.5%) remaining on treatment. Treatment-emergent adverse events (TEAEs) occurred in 35 patients (87.5%), including 14 patients (35.0%) with grade ≥3 (≥G3) TEAEs. Common TEAEs (≥20%) were arthralgia (37.5%, with 2.5% ≥G3), hyperthyroidism (35.0%, all G1-2), rash (32.5%, with 5.0% ≥G3) and hypothyroidism (22.5%, with 2.5% ≥G3). Immune-related adverse events occurred in 24 patients (60.0%, with 20.0% ≥G3). Only 1 patient had TEAEs leading to treatment discontinuation and no patient had TEAEs leading to death. As of September 12^th, 2024, in patients with at least one post-baseline tumor assessment (n=31), overall ORR was 67.7% (95% CI: 50.1–81.4, including 15 of 21 with confirmed response, 4 waiting for confirmation, 2 not confirmed) and DCR was 87.1% (95% CI: 71.1–94.9). In mucosal melanoma (n=20), ORR was 60.0% (95% CI: 38.7–78.1, including 10 of 12 with confirmed response, 2 waiting for confirmation) and DCR was 85.0% (95% CI: 64.0–94.8). The DoR and PFS data were not mature.

Conclusions In conclusion, IBI363 showed encouraging efficacy and manageable safety profile in patients with IO-naïve advanced melanoma. More updates of efficacy and safety data will be presented at the meeting.