1696TiP Phase Ib study to assess the effect of PF-06946860 on appetite following subcutaneous administration in patients with anorexia and advanced cancer

Cachexia is a hypermetabolic multifactorial syndrome characterized by anorexia and loss of weight and skeletal muscle, leading to fatigue, functional impairment, increased treatment-related toxicity, poor quality of life, and reduced survival. Anorexia is a central component of the cachectic phenotype and may be primarily mediated by growth differentiation factor 15 (GDF-15). Neutralization of GDF-15 may improve anorexia and other cancer cachexia-related clinical outcomes. PF-06946860 is a highly potent and selective humanized monoclonal antibody directed against GDF-15. The primary objective of this study (NCT04803305) is to assess the effect of repeated subcutaneous (SC) administration of PF-06946860 on appetite in participants with advanced cancer and elevated circulating GDF-15 concentrations. Secondary objectives include assessing fatigue and safety. Exploratory objectives include evaluating body weight, pharmacokinetics, pharmacodynamics, and immunogenicity. The study will be conducted in 2 parts in approximately 40 adult male or female participants with incurable cancer, including non-small cell lung, pancreatic, colorectal, prostate, breast, and ovarian cancers, as well as anorexia and elevated concentrations of GDF-15. The initial 6-week treatment period will be a randomized, double-blind, placebo-controlled, parallel-group study wherein participants who meet entry criteria will be randomized (2:1) to PF-06946860 or placebo, administered SC every 3 weeks. This period will be followed by an optional open-label treatment with PF-06946860 for up to 18 weeks. The primary outcome measure is change from baseline for the patient-reported 7-day recall Cancer-Related Cachexia Symptom Assessment-Appetite score at Week 4. Secondary outcome measures include patient-reported fatigue (Fatigue score from the Cancer-Related Cachexia Symptom Assessment), adverse events, and laboratory abnormalities. The study is currently recruiting participants in the US, with planned sites in Canada. NCT04803305. Medical writing support was provided by Diane Hoffman, PhD, of Engage Scientific Solutions, and was funded by Pfizer. Pfizer. Pfizer.