Phase I study of the efficacy and safety of IBI319 in patients with advanced malignant tumors.

2646 Background: IBI319 is a recombinant fully human anti-CD137/PD-1 bispecific antibody. In preclinical studies, IBI319 demonstrated a better anti-tumor efficacy and safety. Here we report the initial results from the first-in-human study of IBI319 in patients with advanced malignancies. Methods: Enrolled patients (pts), ECOG PS ≤ 1, had advanced solid tumors or hematological malignancies and failed standard treatment. This phase 1 monotherapy dose-escalation includes accelerated titration (0.03 and 0.1mg/kg) and conventional 3+3 dose escalation (0.3, 1.0, 3.0, 6.0 and 10.0 mg/kg). IBI319 is administered intravenously every 14 days after dose-limiting toxicity (DLT) evaluation. Objectives include evaluation of safety, DLT, pharmacokinetic (PK) and antitumor activity. Adverse events (AEs) were reported per CTCAE v5.0 and DLTs evaluated within a 28-day window. Results: At cutoff date of February 10, 2022, 21 pts were enrolled (median age 55 years; 81.0% male; 19.1% ECOG PS 1; 52.4% advanced solid tumors). The following dose levels have been evaluated; 0.03 mg; 0.1 mg; 0.3 mg; 1 mg; 3 mg and 6 mg. Dose escalation is ongoing. The maximum tolerated dose has not been reached. Treatment-emergent adverse events (TEAEs) was reported in 15 out of 21 (71.4%) pts, among which 1 pts had back pain and nausea of grade 3. The most common TEAEs ( > 10%) were interleukin level increased (6 pts, 28.6%) and C-reactive protein increased (3 pts, 14.3%). Eleven pts (52.4%) experienced treatment-related AEs; none were grade 3 or higher. The most common TRAEs ( > 10%) were interleukin level increased (6 pts, 28.6%) and C-reactive protein increased (3 pts, 14.3%). Importantly, no drug-related elevations in transaminases (ALT, AST) or bilirubin have been seen. No DLT was observed. PK analysis of IBI319 demonstrated consistent exposure with linear PK. For 14 evaluable pts, 1 classical Hodgkin lymphoma patient achieved PR as best response. Conclusions: IBI319 demonstrates good tolerability in patients with advanced solid tumors or hematological malignancies, with a safety profile characterized by a lack of hepatotoxicity frequently observed with CD137-targeting antibodies. Clinical trial information: NCT04708210.