Efficacy and safety of IBI363 monotherapy or in combination with bevacizumab in patients with advanced colorectal cancer.

104 Background: The prognosis of patients (pts) with microsatellite stable/proficient mismatch repair (MSS/pMMR) colorectal cancer (CRC) who failed standard chemotherapy is poor, highlighting a significant unmet need. No immune-oncology therapy has succeeded in this indication due to the "cold" tumor nature. IBI363 is a PD-1/IL-2 α-bias bispecific antibody fusion protein that blocks PD-1 and stimulates tumor-specific T cells that could potentially turn "cold" tumors into "hot" tumors. Methods: The analysis of efficacy and safety data were from 68 pts treated with IBI363 monotherapy and 73 pts treated with IBI363 plus bevacizumab (beva), respectively. Eligible pts were locally advanced unresectable or metastatic CRC who failed or were intolerant to the standard treatment. Data cutoff date was Dec 6, 2024. Results: A total of 68 pts and 73 pts (None were confirmed as microsatellite instability-high/deficient mismatch repair [MSI-H/dMMR]; MSS/pMMR: 86.8% and 90.4%; unknown microsatellite/MMR status: 13.2% and 9.6%; liver metastases: 61.8% and 54.8%; KRAS/NRAS mutations: 42.6% and 41.1%; previous treatment lines ≥ 3: 63.2% and 53.4%; previous immunotherapy: 27.9% and 16.4%) were treated with IBI363 monotherapy (0.1 mg/kg to 3 mg/kg every week [QW], every 2 weeks [Q2W] or every 3 weeks [Q3W]) and IBI363 plus beva (0.6 or 1 mg/kg Q2W, 1.5, 2 or 3 mg/kg Q3W, plus beva 5 mg/kg Q2W or 7.5 mg/kg Q3W), respectively. Median follow-up time was 11.8 months (range: 0.4–22.5) for monotherapy and 5.1 months (range: 1.2–14.9) for combination. In efficacy-evaluable pts (n = 63 for monotherapy and n = 68 for combination), the objective response rate (ORR) was 12.7% (95% confidence interval [CI]: 5.6–23.5) and 23.5% (95% CI: 14.1–35.4). The median duration of response was 7.5 months (95% CI: 1.2–19.6) for monotherapy and not mature for combination. The median OS was 16.1 months (95% CI: 10.1–not reached) for monotherapy and not mature for combination. Especially, in pts without liver metastasis who received the combination therapy (n = 31), the ORR was 38.7% (95% CI: 21.9–57.8), the DCR was 83.9% (95% CI: 66.3–94.6), and median PFS was 9.6 months (95% CI: 4.1–12.2). Grade ≥ 3 treatment-related adverse events were reported in 16 (23.5%) pts with monotherapy and 22 (30.1%) pts with combination. Arthralgia, rash, and thyroid disorders were commonly reported immune-related adverse events. Conclusions: IBI363 monotherapy demonstrated prolonged overall survival in pts with advanced CRC compared to historic data of standard of care. IBI363 plus beva showed even more encouraging efficacy with acceptable safety and warrants further development. Clinical trial information: NCT05460767 .