LBA82 - Efficacy and safety of ponsegromab, a first-in-class, monoclonal antibody inhibitor of growth differentiation factor 15, in patients with cancer cachexia: A randomized, placebo-controlled, phase II study

Background

Ponsegromab is a humanized monoclonal antibody targeting growth differentiation factor 15 (GDF-15), a circulating cytokine implicated in cachexia. We report the results of a phase 2, randomized, double-blind trial of ponsegromab vs placebo in patients with cancer cachexia.

Methods

Patients with cancer cachexia and elevated serum GDF-15 (≥1500 pg/mL) 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 in weight from baseline to 12 weeks. Other endpoints included change in appetite and cachexia symptoms (Anorexia Cachexia Subscale and 5-item Anorexia Symptom Scale of the Functional Assessment of Anorexia/Cachexia Treatment [FAACT] instrument), digital measures of physical activity (including non-sedentary physical activity, total vector magnitude), and lumbar skeletal muscle index (LSMI).

Results

Overall, 187 patients (39.6% non-small cell lung, 31.6% pancreatic, and 28.9% colorectal cancer; 73.3% stage 4) were randomized. Ponsegromab resulted in significant dose-responsive increases in weight, with placebo-adjusted modeled median (90% credible interval) increases of 1.33 kg (0.49, 2.34) [100 mg], 2.08 kg (1.08, 3.15) [200 mg] and 3.00 kg (1.68, 4.34) [400 mg] at 12 weeks. Placebo-adjusted weight gain was observed from week 4 in all ponsegromab groups. Improvements across symptoms, overall activity, and LSMI were observed in the 400 mg group relative to placebo. All-causality and treatment-related adverse events occurred in 70.4% and 7.7% of ponsegromab-treated patients and 80.0% and 8.9% of placebo-treated patients, respectively. Table: LBA82

*Scale ranges from 0 to 48 (higher scores indicate a better outcome). †Scale ranges from 0 to 20 (higher scores indicate a better outcome).

Conclusions

Ponsegromab improved weight, symptoms, overall activity, and skeletal muscle mass in patients with cancer cachexia and elevated GDF-15, confirming GDF-15 as a primary driver of cancer cachexia.

Clinical trial identification

NCT05546476. First posted September 19, 2022.

Editorial acknowledgement

Medical writing support was provided by Alex Frings, PharmD, CMPP, of Engage Scientific Solutions and was funded by Pfizer Inc.

Legal entity responsible for the study

Pfizer.

Funding

Pfizer.

Disclosure

J. Crawford: Financial Interests, Personal, Speaker, Consultant, Advisor: Actimed, BIO Alta, Enzychem, Faraday, G1 Therapeutics, Pfizer, Tensegrity; Financial Interests, Institutional, Research Funding: AstraZeneca, Helsinn Healthcare, Pfizer. J.D. Groarke: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. S.M. Collins: Financial Interests, Personal, Stocks/Shares: Pfizer; Financial Interests, Personal, Full or part-time Employment: Pfizer. S. Lubaczewski: Financial Interests, Personal, Stocks/Shares: Pfizer; Financial Interests, Personal, Full or part-time Employment: Pfizer. E.J. Roeland: Financial Interests, Personal, Advisory Board: Napo Pharmaceuticals, Actimed Therapeutics, Meter Health, Veloxis Therapeutics, BYOMass, Takeda, Enzychem Lifesciences; Financial Interests, Institutional, Local PI: Pfizer, Napo Pharmaceuticals; Non-Financial Interests, Member, Evidence-based Guidelines committee: American Society of Clinical Oncology. T. Naito: Financial Interests, Personal, Speaker, Consultant, Advisor: Pfizer, Ono Pharmaceutical; Financial Interests, Institutional, Research Funding: Kracie holdings. A.E. Hendifar: Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Institutional, Local PI: Merck, Pfizer, Faeth, cantex, inspirna, elicio; Financial Interests, Personal, Other, I am on the DSMC: rayzebio; Non-Financial Interests, Advisory Role, SMAB: PANCAN. M.T. Fallon: Financial Interests, Institutional, Advisory Board: Ananda Developments; Financial Interests, Personal, Advisory Board: Pfizer. K. Takayama: Financial Interests, Personal, Speaker, Consultant, Advisor: Ono Pharmaceutical, AstraZeneca; Financial Interests, Personal, Other, Honoraria: Eli Lilly, Ono Pharmaceutical, AstraZeneca, Chugai Pharmaceutical, Boehringer Ingelheim, MSD-Merck, Daiichi Sankyo, Pfizer; Financial Interests, Institutional, Research Funding: Taiho Pharmaceutical, Eli Lilly. T.R. Asmis: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Bristol Myers Squibb, Eisai, Knight Therapeutics, Ipsen, Medison, Merck, Novartis, Pfizer. R.F. Dunne: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck, Toray Industries Inc., Exelixis Inc. M. Rossulek, R. Qiu, A.R. Saxena: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer.