PF-06801591, a humanized IgG4 monoclonal antibody, blocks the Programmed Cell Death (PD-1) pathway by binding with high affinity to PD-1 and preventing its interaction with its ligands. A phase 1 study to assess the safety and tolerability of PF-06801591 after IV or SC administration is ongoing in patients (pts) with locally advanced or metastatic solid tumors.
PF-06801591 was administered at 0.5, 1, 3, or 10 mg/kg IV once every 3 weeks (q3w), or 300 mg SC once every 4 weeks (q4w). Dose escalation occurred after the first 2-4 pts at each dose cohort, with additional pts then enrolled to each cohort for further PD assessment. Safety, tolerability, PK, and PD were assessed for all pts.
As of January 31, 2017, 26 pts (ovarian cancer, n = 12; sarcoma, n = 6; head and neck cancer [SCCHN]; n = 5; melanoma, n = 1; small cell lung cancer, n = 1; and malignant peritoneal neoplasm, n = 1) were treated in the dose-escalation phase: 0.5 (n = 2), 1 (n = 8), 3 (n = 7), 10 (n = 5) mg/kg IV, and 300 mg (n = 4) SC. Maximum tolerated dose was not reached. No drug-related SAEs or dose-limiting toxicities were observed. All drug-related AEs were Grade 1 or 2, and the most frequently reported in > 15% of pts include nausea (15.4%) and fatigue (15.4%). No dose-dependency of AEs was observed during IV dose escalation nor serious skin toxicity with SC administration. Four pts had partial response at 0.5, 1, and 10 mg/kg IV (ovarian pts) and 300 mg SC (SCCHN pt) and 3 pts had stable disease lasting >24 wks. There was a dose-dependent increase in the maximum concentration (Cmax) and area under the concentration-time curve (AUC) after IV administration. Following SC administration, PF-06801591 was slowly absorbed, with a median time to Cmax of 182 hours. The mean average concentration (Cav) after the first SC dose at 300 mg q4w was approximately 50% of the mean Cav following IV administration at 3 mg/kg q3w. Full receptor occupancy of PD-1 was seen in all dose cohorts.
Preliminary results demonstrate that PF-06801591 is well-tolerated with objective responses observed across the dose levels tested in both IV and SC forms. PK data confirmed the appropriateness of the dosing frequency.
Clinical trial identification
Legal entity responsible for the study
S. Hu-Lieskovan: Consulting: Amgen, Merck, Novartis, Vaccinex, Emergent BioSolutions Contracted Research: Pfizer, Plexxikon, Genentech, Neon Therapeutics Research Support: Bristol-Myers Squibb, Merck Travel Support: Amgen, Merck, Novartis, Vaccinex, Emergent BioSolutions, Neon Thera. M. Johnson: Research funding (institution): OncoMed, BerGenBio, Lilly, EMD Serono, Kadmon, Janssen, Mirati, Genmab, Pfizer, AstraZeneca, Genentech/Roche Stemcentrix, Novartis, and others; compensation (institution) from Genentech/Roche, Celgene and Boehringer Ingelheim. F.S. Braiteh: Speaker and advisor/consultant for Pfizer. J. Grilley-Olson: Only disclosures are for Institutional research funding from: Pfizer, Genentech, Novartis, Seattle Genetics, Medimmune, Nanocarrier. J. Chou J. Davda, B. Jin, A. Forgie: Employed by Pfizer and own Pfizer stock. D. Rassam, S. Youssef: Pfizer consultant but privately own Pfizer stock.