Efficacy and safety of ponsegromab in patients with colorectal cancer and cachexia: A subgroup analysis of the PROACC-1 phase 2 study.

110 Background: Ponsegromab is a monoclonal antibody that inhibits growth differentiation factor 15 (GDF-15), a circulating cytokine implicated in cachexia. Here, we report the body weight and safety findings from the subset of participants with colorectal cancer (CRC) in a phase 2, randomized, double-blind trial of ponsegromab versus placebo in patients with cancer cachexia (PROACC-1; NCT05546476). Methods: Patients with cancer, cachexia, and elevated serum GDF-15 (≥1500 pg/mL) (n=187) were randomized 1:1:1:1 to subcutaneous ponsegromab (100, 200, 400 mg) or matching placebo every 4 weeks for 12 weeks. The primary endpoint was a change from baseline (CFB) in body weight at 12 weeks. Safety and tolerability were key secondary endpoints. Results: Overall, 54 participants (28.9% of the overall study population) had CRC (mean age 65.1±11.9 years; 61.1% male; 81.5% stage IV). Baseline mean body weight was 56.5±13.3 kg; 51.9% and 48.1% had a body mass index