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

3593 Background: The prognosis of advanced colorectal cancer (CRC) is poor with limited treatment options available. IBI363 is a PD-1/IL-2 α-bias bispecific antibody that specifically activate PD-1(+)CD25(+) tumor specific T cells while sparing PD-1(-)CD25(-) bystander T cells, and activate peripheral regulatory T cells to protect the body from autoimmunity. Herein, we report the safety and efficacy of IBI363 in patients (pts) with advanced CRC in a phase I study. Methods: Eligible pts with locally advanced or metastatic CRC who failed or intolerant to standard treatment were enrolled and received IBI363 intravenously at dose levels ranging from 100 ug/kg to 3 mg/kg every week (QW), every two weeks (Q2W) or every three weeks (Q3W). The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), etc. per RECIST v1.1. Results: As of December 22, 2023, a total of 68 pts (males: 55.9%, median age: 55.5 years, ECOG PS 1: 50.0%, liver metastasis: 61.8%; previous treatment ≥3 lines: 76.5%; previous immunotherapy: 27.9%) were recruited and received IBI363 treatment including 26 pts at 600 µg/kg Q2W and 22 pts at 1 mg/kg Q2W. Microsatellite stable (MSS)/proficient mismatch repair (pMMR) was presented in 57 (83.8%) pts and microsatellite status of the remaining 11 (16.2%) pts were unknown. Median follow up time was 5.3 months (95%CI: 4.4-6.9). Treatment emergent adverse events (TEAEs) were reported in 65 (95.6%) pts including grade ≥3 TEAEs in 22 (32.4%) pts. Common TEAEs (≥20%) were arthralgia (35.3%), anemia (32.4%), pyrexia (22.1%) and hypoalbuminemia (20.6%). Treatment related adverse events (TRAEs) were reported in 62 (91.2%) pts including grade ≥3 TRAEs in 16 (23.5%) pts. Immune related adverse events (irAEs) were reported in 22 (32.4%) pts including grade ≥3 irAEs in 4 (5.9%) pts. Serious TRAE were reported in 12 (17.6%) pts. TRAEs leading to treatment interruption and discontinuation were reported in 25 (36.8%) and 2 (2.9%) pts. No TRAE leading to death was reported. Pts with at least 1 post-baseline tumor assessment were included in efficacy evaluable set. In all evaluable pts (n=63), overall ORR was 12.7% (95%CI: 5.6-23.5). In pts with liver metastasis (n=38), ORR was 13.2% (95%CI: 4.4-28.1). In pts with PD-L1 CPS ≥1 (n=13), ORR was 30.8% (95%CI: 9.1-61.4), and DCR was 76.9% (95%CI: 46.2-95.0). The median DoR was not reached. A prospective cohort of CRC pts with PD-L1 CPS ≥1 has been initiated. Further details and data will be updated at the meeting. Conclusions: IBI363 showed acceptable tolerability and manageable safety profiles in pts with advanced CRC. Preliminary efficacy of IBI363 was observed, particularly in pts with PD-L1 CPS ≥1. Clinical trial information: NCT05460767 .