Trial results for ponsegromab in patients with cancer, cachexia, and elevated GDF-15 were posted on ClinicalTrials.gov on 2025-04-29. The Phase 2 study indicated that ponsegromab led to a posterior median body weight increase of up to 3.0 kg compared to placebo in some dose groups.
Background
The study, titled "Study of the Efficacy and Safety of Ponsegromab in Patients With Cancer, Cachexia and Elevated GDF-15," investigated the drug in individuals suffering from cancer-related cachexia, characterized by conditions such as Non-small Cell Lung Cancer, Pancreatic Cancer, Colorectal Cancer, Loss of Appetite, and Fatigue, along with elevated GDF-15 levels.
Trial design
The Phase 2 study (NCT05546476) was a randomized, placebo-controlled trial that enrolled 187 participants. The trial evaluated the efficacy, safety, and tolerability of ponsegromab compared to placebo in patients with cancer, cachexia, and elevated GDF-15. Participants included those with Non-small Cell Lung Cancer, Pancreatic Cancer, and Colorectal Cancer, experiencing symptoms like Loss of Appetite and Fatigue. The interventions included ponsegromab at doses of 100 mg, 200 mg, and 400 mg, as well as placebo.
Key results
Key results from the trial included analyses of body weight and physical activity. For body weight, using a Bayesian Emax model, the differences in posterior median relative to placebo (measured in kilograms) were observed:
- A difference of 1.33 kg (90% credible interval: 0.49 to 2.34) in one dose group.
- A difference of 2.08 kg (90% credible interval: 1.08 to 3.15) in another dose group.
- A difference of 3.0 kg (90% credible interval: 1.68 to 4.34) in a third dose group.
These differences suggest an increase in body weight compared to placebo, with the highest observed difference being 3.0 kg. No adjustments were made for multiplicity in these calculations.
Regarding changes from baseline in physical activity at Week 12, measured in minutes per day, the least squares mean values were:
- For placebo, a change of -1.42 minutes per day.
- For ponsegromab 100 mg, a change of 51.93 minutes per day.
- For ponsegromab 200 mg, a change of -39.33 minutes per day.
- For ponsegromab 400 mg, a change of -3.37 minutes per day.
A second set of measurements for physical activity showed:
- For placebo, a change of -37.73 minutes per day.
- For ponsegromab 100 mg, a change of 0.03 minutes per day.
- For ponsegromab 200 mg, a change of -42.09 minutes per day.
- For ponsegromab 400 mg, a change of 12.11 minutes per day.
Further analyses on sedentary activity time, using an MMRM model, reported differences in LS Mean relative to placebo (measured in minutes per day):
- A difference of 53.36 minutes per day (90% confidence interval: -40.89 to 147.6) with a 1-sided p-value of 0.826.
- A difference of -37.9 minutes per day (90% confidence interval: -132.94 to 57.14) with a 1-sided p-value of 0.254.
- A difference of -1.95 minutes per day (90% confidence interval: -101.63 to 97.73) with a 1-sided p-value of 0.487.
What this means
The trial results suggest that ponsegromab may have a positive effect on body weight in patients with cancer cachexia and elevated GDF-15, with some dose groups showing an increase in posterior median body weight compared to placebo. While some physical activity measurements showed increases in certain ponsegromab groups, the overall findings for physical activity and sedentary time were mixed and did not consistently demonstrate a statistically significant benefit over placebo across all doses or analyses. These findings provide initial insights into the potential role of ponsegromab in managing cancer-related cachexia, particularly regarding body weight.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05546476, titled "Study of the Efficacy and Safety of Ponsegromab in Patients With Cancer, Cachexia and Elevated GDF-15," were posted on 2025-04-29 on clinicaltrials.gov.