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

e14593 Background: IBI363 is a first-in-class PD-1/IL-2 α -bias bispecific antibody fusion protein which could block PD-1 checkpoint and rejuvenate exhausted tumor-specific T cells by cis-activating α-bias IL-2. It was well tolerated and showed encouraging efficacy in patients (pts) with advanced melanoma, non-small cell lung cancer and colorectal cancer. Herein, we report a phase I study of IBI363 in patients (pts) with other solid tumors. Methods: Eligible pts with advanced biliary tract cancer (BTC), head and neck squamous cell carcinoma (HNSCC), cervical cancer (CC) and ovarian cancer (OC) who failed or intolerant to standard therapy were enrolled. IBI363 was intravenously administered at different dose levels ranging from 600 to 1500 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) and disease control rate (DCR). Results: As of January 26, 2024, 24 pts were enrolled including 13 pts with BTC, 3 pts with HNSCC, 4 pts with CC and 4 pts with OC. In BTC, 6 (46.2%) pts received IBI363 treatment for more than 3 months and the maximum treatment duration was 7 months. In HNSCC, CC and OC, the maximum treatment duration was 4.6, 6.2 and 6.5 months respectively. Pts with at least 1 tumor assessment were included in efficacy evaluable set (n = 18). The overall ORR was 22.2% and DCR was 77.8%. In 11 evaluable pts with BTC, best overall response (BOR) was confirmed partial response (cPR) in 1 pt (600 μg/kg Q2W, immunotherapy (IO)-failed), stable disease (SD) in 9 pts (including 6 pts with tumor regression) and progressive disease (PD) in 1 pt. ORR was 9.1% and DCR was 90.9%. In 2 evaluable pts with HNSCC, 1 pt had cPR (600 μg/kg Q2W, IO-naïve, PD-L1 expression negative) and 1 pt had PD. In 3 evaluable pts with CC, 1 pt had cPR (1000 μg/kg Q2W, IO-failed), 1 pt had SD and 1 pt had PD. In 2 evaluable pts with OC, 1 pt had cPR (1000 μg/kg Q2W, platinum-resistant) and 1 pt had PD. All cPR pts had previous 1-2 lines of treatments and had tumor regression ranging from 45% to 87%. Durable tumor responses were observed with cPR remained at week 30 in BTC and remained at week 24 in HNSCC, CC and OC. In 4 pts with cPR, 3 pts still on treatment and 1 pt with HNSCC received curative resection. No new safety signals of IBI363 were observed. More updated data on safety and efficacy will be presented at the meeting. Conclusions: IBI363 showed promising and durable efficacy in pts with various solid tumors including refractory tumors such as BTC and IO or platinum-resistant tumors such as CC and OC. Further clinical investigations on these tumors using IBI363 alone or in combination with other treatments are ongoing. Clinical trial information: NCT05460767 .