A phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab in patients with advanced solid tumors

Area of Science:

• Immunotherapy
• Oncology
• Clinical Pharmacology

Background:

• Simultaneous inhibition of PD-1 and CTLA-4 with bispecific antibodies offers a potential strategy to enhance anti-tumor efficacy compared to single-agent therapies.
• Bispecific antibodies can target multiple immune checkpoints, potentially leading to synergistic effects and improved safety profiles.

Purpose of the Study:

• To evaluate the safety, tolerability, and preliminary efficacy of cadonilimab, a novel bispecific antibody targeting PD-1 and CTLA-4.
• To determine the recommended dose for future clinical studies of cadonilimab in patients with advanced solid tumors.

Main Methods:

• A Phase 1 clinical trial involving dose escalation (n=39) and dose expansion (n=80) cohorts.
• Assessment of safety, including dose-limiting toxicities and treatment-related adverse events.
• Evaluation of efficacy through overall response rate and duration of response.

Main Results:

• The maximum tolerated dose was not reached; 6 mg/kg every 2 weeks was established as the recommended dose.
• Infusion-related reactions were the most common adverse event (18.5%), primarily grade 1/2.
• The overall response rate was 13.4%, with a median duration of response of 12.9 months. Immune-related adverse events occurred in 44.5% (any grade) and 6.7% (grade ≥3).

Conclusions:

• Cadonilimab is well-tolerated in patients with advanced solid tumors.
• The bispecific antibody demonstrated promising anti-tumor activity, supporting further investigation in clinical trials.
• Simultaneous PD-1 and CTLA-4 inhibition with cadonilimab represents a potential therapeutic advancement in cancer immunotherapy.