First-in-class PD-1/IL-2 bispecific antibody fusion protein IBI363 in patients with advanced melanoma: Safety and efficacy results from a phase I study.

9562 Background: Despite great success of immunotherapy (IO) in advanced melanoma, there remains unmet clinical needs for IO resistant and cold tumors. IBI363 is a first-in-class PD-1/IL-2 α -bias bispecific antibody fusion protein which could block PD-1 checkpoint and activate α-bias IL-2 to rejuvenate exhausted tumor-specific T cells. Herein, we report updated results from the phase I study to evaluate safety and efficacy of IBI363 in pts with advanced melanoma. Methods: Eligible pts with advanced melanoma who failed or intolerant to standard therapy were enrolled to receive IBI363 intravenously at different dose levels ranging from 100-2000 μg/kg QW/Q2W/Q3W. Primary objective of the study was safety. Secondary objective was efficacy assessed by investigator per RECIST v1.1 including objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and progression free survival (PFS). Results: As of January 11, 2024, 67 pts were enrolled (females: 55.2%, median age: 59.0 years, ECOG PS 1: 74.6%, prior treatment lines ≥2: 59.7%, prior IO: 89.6%). There were 17 pts with cutaneous melanoma, 22 pts with acral melanoma, 25 pts with mucosal melanoma and 3 pts with unknown primary melanoma. The median treatment duration was 12.0 weeks (range: 2.0-43.6) with 38 pts (56.7%) still on treatment. Most comment reason for end of treatment was disease progression in 25 pts (37.3%). All pts were included in safety analysis. Treatment-emergent adverse events (TEAEs) occurred in 63 (94.0%) pts. Grade ≥3 TEAEs and TRAEs occurred in 16 (23.9%) and 12 (17.9%) pts. Common TEAEs (≥20%) were arthralgia (34.3%), hyperthyroidism (29.9%), anemia (25.4%). TEAE leading to treatment discontinuation occurred in 1 (1.5%) pt.No pts had TEAEs leading to death. Pts with at least 1 post-baseline tumor assessment were included in efficacy evaluable set. In all evaluable pts (n=57), the best overall response was complete response (CR) in 1 pt, partial response (PR) in 15 pts, stable disease (SD) in 25 pts and progressive disease (PD) in 16 pts. The overall ORR was 28.1% (95%CI: 17.0-41.5%) and DCR was 71.9% (95%CI: 58.5-83.0). In pts had prior IO (n=52), ORR was 21.2% (95%CI: 11.1-34.7) and DCR was 67.3% (95%CI: 52.9-79.7). In 1 mg/kg Q2W pts had prior IO (n=25), ORR was 32.0% (95%CI: 14.9-53.5) and DCR was 80.0% (95%CI: 59.3-93.2). The DoR and PFS data were immature at the time of analysis. Biomarker analysis in baseline tumor region observed significantly higher CD8 T cell infiltration (measured by cell positivity and density) in PR/SD patients than PD patients (p<0.05). More updated data on safety and efficacy will be presented at the meeting. Conclusions: In pts with advanced melanoma, IBI363 showed encouraging efficacy in different tumor subtypes and in pts wit prior IO. The safety profiles were acceptable and manageable. Further clinical development of IBI363 in melanoma are ongoing both in China and overseas. Clinical trial information: NCT05460767 .