574P - First-in-class PD-1/IL-2 bispecific antibody fusion protein IBI363 + bevacizumab (beva) in patients (pts) with advanced colorectal cancer (CRC): A phase I study

Background

IBI363 is a PD-1/IL-2^α-bias bispecific antibody fusion protein which can block the PD-1 checkpoint and rejuvenate exhausted tumor-specific T cells by cis-activating the α-bias IL-2 receptor. IBI363 monotherapy showed acceptable safety and efficacy in pts with advanced non-microsatellite instability high/deficient mismatch repair (non-MSI-H/dMMR) CRC (Chen et al, abstract No. 3593 at 2024 ASCO annual meeting). We report initial safety and efficacy results of IBI363 + beva biosimilar in pts with advanced CRC in a phase I study.

Methods

Eligible pts with locally advanced or metastatic CRC (non-MSI-H/dMMR) who failed or intolerant of standard treatment were enrolled to receive IBI363 intravenously at 0.6-1.5 mg/kg + beva at 5/7.5 mg/kg. Primary objective was safety and tolerability; secondary objective was antitumor activity per RECIST v1.1. Data cutoff date was Apr 19, 2024.

Results

A total of 35 pts (males: 57.1%, median age: 53.0 yrs, liver metastasis: 54.3%; previous treatment lines ≥3: 62.9%; previous immunotherapy [IO]: 25.7%) were enrolled, including 3 pts at 0.6 mg/kg Q2W, 25 pts at 1 mg/kg Q2W, and 7 pts at 1.5 mg/kg Q3W. MSS was presented in 82.9% pts and microsatellite status were unknown in the remaining pts. Median treatment exposure was 8.9 weeks (range: 2.0-37.3). Treatment-emergent adverse events (TEAEs) occurred in all pts, with grade ≥3 TEAEs in 6 (17.1%) pts. Most common TEAEs (≥20%) were arthralgia (42.9%), rash (31.4%), cough (25.7%), hyperthyroidism (25.7%), myalgia (22.9%), and hypothyroidism (20.0%). Immune-related adverse events (irAEs) occurred in 9 (25.7%) pts including grade ≥3 irAEs in 1 (2.9%) pts. TEAE led to treatment discontinuation and death in 1 (2.9%) pts each. In 32 efficacy-evaluable pts (defined as pts with ≥1 post-baseline tumor assessment), ORR was 18.8% (95%CI: 7.2-36.4) and DCR was 65.6% (95%CI: 46.8-81.4). In 17 pts with liver metastasis, ORR and DCR were 11.8% (95%CI: 1.5-36.4) and 58.8% (95%CI: 32.9-81.6), respectively. In 8 IO-treated pts, ORR and DCR were 25.0% (95%CI: 3.2-65.1) and 62.5% (95%CI: 24.5-91.5), respectively.

Conclusions

IBI363 + beva showed acceptable safety and encouraging efficacy in pts with advanced CRC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Innovent Biologics (Suzhou) Co., Ltd.

Funding

Innovent Biologics (Suzhou) Co., Ltd.

Disclosure

M. Yuan, L. Zhao, H. Wang, C. Wei, L. Ding, Y. Chen, H. Zhou: Financial Interests, Personal and Institutional, Full or part-time Employment: Innovent Biologics (Suzhou) Co., Ltd. All other authors have declared no conflicts of interest.