Baseline circulating growth differentiation factor-15 and the cancer phenotype in the PROACC-1 phase 2 study of the efficacy and safety of ponsegromab in patients with cancer cachexia.

Abstract

12060 Background: Growth differentiation factor-15 (GDF-15) is an emerging therapeutic target in cancer cachexia. However, the association of circulating GDF-15 with the cancer cachexia phenotype remains poorly characterized. Methods: Serum GDF-15 was measured using the Roche Elecsys GDF-15 assay at screening in a phase 2, randomized trial of ponsegromab (an investigational anti-GDF-15 monoclonal antibody) in patients with cancer cachexia, and an elevated serum GDF-15 (≥ 1500 pg/mL) (NCT05546476). Cachexia was defined by international consensus criteria and sarcopenia by standardized sex-specific cut-off values for lumbar skeletal muscle index. Cross-sectional associations of GDF-15 with various demographic and clinical parameters were explored post-hoc using summary statistics and Pearson’s correlation (with GDF-15 on the log 10 scale). Results: A total of 187 patients were enrolled in this study with a median (IQR) age of 67 (60-74) years and 37% were female. Baseline median GDF-15 values were higher among patients with cachexia and colorectal and pancreatic cancers, compared to NSCLC. GDF-15 elevation was higher in patients with stage IV disease, sarcopenia, and worse performance status (Table). Higher GDF-15 levels were associated with lower serum albumin (r = -0.31 [95% CI: -0.44, -0.177]) and pre-albumin (r = -0.17 [95% CI: -0.31, -0.03]). No significant associations were observed between GDF-15 levels and appetite or fatigue assessments. Conclusions: Among patients with cancer cachexia, GDF-15 elevation was more pronounced in those with more advanced cancer, sarcopenia, and worse performance status. In addition, GDF-15 levels were negatively correlated with markers of nutritional status. Clinical trial information: NCT05546476 . Demographic or Clinical Characteristic n Median (IQR) serum GDF-15, pg/ml Age, years- 18-44- 45-64- ≥65 670111 2718 (2461, 8117)4197 (2366, 9425)3849 (2310, 7125) Type of cancer- NSCLC- Pancreatic- Colorectal 745954 2701 (2114, 4094)4714 (2408, 9561)6468 (4106, 10052) Interval from cancer diagnosis- <1 year- ≥1 year 9691 4259 (2447, 8919)3781 (2259, 6997) Stage of cancer- I/II- III- IV 1634137 3551 (2264, 6320)3232 (2461, 5704)4365 (2387, 8117) Body mass index (BMI), kg/m2- <20- ≥20 9988 3254 (2220, 6801)5052 (2712, 8749) % weight loss in 6 months prior to screening- < 10%- ≥ 10% 9988 3849 (2290, 7677)4118 (2381, 7595) Sarcopenia status- Yes- No 14440 4259 (2402, 7672)2928 (2136, 8052) ECOG Performance Status- 0- 1- 2/3 3312331 2842 (2408, 5673)4094 (2366, 8623)5119 (2272, 7667) Systemic anticancer therapy- Platinum-based therapy- Antimetabolite agents- Biological agents- Antimicrotubule agents- PD-1 or PD-L1 inhibitors 68100407330 5760 (3053, 10008)5914 (2847, 10768)5744 (3317, 9644)4891 (2762, 9425)2744 (2149, 4787)