Phase Ia dose escalation of IBI318, a first-in-class bispecific anti-PD-1/PD-L1, in patients with advanced tumors

3062 Background: With the proven success of PD-1 and PD-L1 monoclonal antibodies, exploiting antibody based immune checkpoint strategies has potential to reduce disease burden and improve patient survival outcome. IBI318, as a first-in-class anti-PD-1/PD-L1 bispecific antibody, could provide more potent anti-tumor activity and more durable response. Here we report preliminary results from an ongoing phase 1a/1b study of IBI318 in advanced tumors. Methods: In the dose escalation of Phase 1a, patients with advanced and/or refractory solid tumors or hematological malignancies were enrolled to receive IBI318. Dose escalation was from 0.3 mg to 600 mg (8 cohorts) via an accelerated titration followed by a modified toxicity probability interval-2 design with a 28-day dose-limiting toxicity (DLT) observation period. Patients without DLT will receive IBI318 every two week (Q2W). Tumor assessments were performed every 6 weeks. Results: As of Jan 10, 2020, 15 pts who had failed at least one line of treatment had been enrolled (1 pt each in 0.3 mg, 1 mg, 3 mg and 10 mg; 3 pts in 30 mg; 3 pts in 100 mg, 3 pts in 300 mg and 2 pts in 600 mg) for dose escalation and received at least 1 dose of treatment. Median duration of treatment was 6.1 (range: 2.1-24.7) weeks. IBI318 had been well tolerated with no DLT from 0.3mg to 300mg group. 11 of 15 pts had treatment related AEs (TRAEs) and the most common (≥10%) TRAEs were pyrexia (20.0%, G1/2) and infusion-related reaction (20.0%, G1/2). 1 patient in 300 mg had an immune-related AE (G2 arthritis). No ≥G3 TRAE had been observed. 12 pts had at least one on-study tumor assessment. 3 of 9 pts receiving dose level ≥10mg had achieved partial response (1 confirmed, 1 pending confirmation and the other PD after the first PR scan). A total of 10 pts discontinued treatment due to disease progression (8) and AE (2, G4 lung infection and G4 upper gastrointestinal hemorrhage, both were not related to treatment). Conclusions: IBI318 has shown an acceptable safety profile. Preliminary efficacy results are promising in advanced cancer patients. The study is currently ongoing at dose level of 600 mg Q2W. Clinical trial information: NCT03875157 .