A Phase 1b First-In-Patient Study Assessing the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Ponsegromab in Participants with Cancer and Cachexia
Mené sur 10 patients atteints d'un cancer de stade avancé, présentant une cachexie et une concentration sérique élevée de GDF-15, cet essai de phase IB détermine la dose maximale tolérée du ponségromab (un anticorps anti-GDF-15) et analyse ses caractéristiques pharmacocinétiques et pharmacodynamiques
Purpose: Cachexia is common in patients with advanced cancer and is associated with elevated serum growth differentiation factor 15 (GDF-15) concentrations. This first-in-patient (phase Ib), 24-week study assessed use of ponsegromab, a monoclonal antibody against GDF-15, in adults with advanced cancer, cachexia, and elevated GDF-15 serum concentration. Experimental Design: Participants (n = 10 received open-label ponsegromab subcutaneous 200 mg every 3 weeks for 12 weeks in addition to standard-of-care anti-cancer treatment Ponsegromab safety, tolerability, and pharmacokinetics were assessed in addition to serum GDF-15 concentrations and exploratory measures of efficacy. Results: No treatment-related treatment-emergent adverse events, injection site reactions, or adverse trends in clinical laboratory tests, vital signs, or electrocardiogram parameters attributable to ponsegromab were identified Median serum unbound GDF-15 concentration at baseline was 2.269 ng/mL Following initiation of study treatment, median unbound GDF-15 concentrations were below the lower limit of quantification (0.0424 ng/mL) from day 1 (3 hours post-dose) through week 15 Increases in body weight were observed at all time points during the treatment and follow-up. A least-squares mean (standard error) increase of 4.63 kg (1.98) was observed at week 12, an increase of approximately 6.6% relative to baseline Ponsegromab-mediated improvements in actigraphy-based assessments of physical activit and in quality of life, including appetite as assessed by Functional Assessment of Anorexia-Cachexia Therapy total and subscale scores, were also observed. Conclusions: Ponsegromab was well tolerated, suppressed serum GDF-15 concentrations, and demonstrated preliminary evidence of efficacy These findings support the continued development of ponsegromab for the treatment of cachexia. ClinicalTrials.gov: NCT04299048