TY - JOUR
T1 - First-in-human study of PF-06647020 (cofetuzumab pelidotin), an antibody-drug conjugate targeting protein tyrosine kinase 7, in advanced solid tumors
AU - Maitland, Michael L.
AU - Sachdev, Jasgit C.
AU - Sharma, Manish R.
AU - Moreno, Victor
AU - Boni, Valentina
AU - Kummar, Shivaani
AU - Stringer-Reasor, Erica
AU - Lakhani, Nehal
AU - Moreau, Allison R.
AU - Xuan, Dawei
AU - Li, Ray
AU - Powell, Eric L.
AU - Jackson-Fisher, Amy
AU - Bowers, Michelle
AU - Alekar, Shilpa
AU - Xin, Xiaohua
AU - Tolcher, Anthony W.
AU - Calvo, Emiliano
N1 - Funding Information:
M.L. Maitland reports institutional research funding to Inova Health System from Pfizer. J.C. Sachdev reports personal fees and other support from Pfizer during the conduct of the study, as well as personal fees from Novartis, Puma, AstraZeneca, Tempus, and Immunomedics outside the submitted work. M.R. Sharma reports institutional research funding to START Midwest from Pfizer, as well as ownership of Pfizer stock. V. Moreno reports personal fees from Roche, Janssen, Bayer, BMS, and Basilea outside the submitted work. V. Boni reports institutional funding from Pfizer during the conduct of the study. V. Boni also reports personal fees (consultant/ advisory boards) from Oncoart, Ideaya, Loxo Therapeutics, CytomX Therapeutics, Puma Biotechnology, and Guidepoint, as well as institutional funding from AbbVie, ACEO, Adaptimmune, Amcure, Amgen, AstraZeneca, BMS, CytomX, GSK, Gen-entech/Roche, H3, Incyte, Janssen, Kura, Lilly, Loxo, Nektar, Macrogenics, Menarini, Merck, Merus, Nanobiotix, Novartis, Pfizer, PharmaMar, Principia, Puma, Sanofi, Taiho, Tesaro, BeiGene, Transgene, Takeda, Incyte, Innovio, MSD, PsiOxus, Seattle Genetics, Mersana, Daiichi, Nektar, Astellas, Orca, Boston Therapeutics, Dynavax, DebioPharm, Boehringer Ingelheim, Regeneron, Millennium, Synthon, Spectrum, Rigontec, and Zenith outside the submitted work. S. Kummar reports other support from Boehringer Ingelheim, Springworks Therapeutics, Bayer, Genome & Company, HarbourBiomed, Seattle Genetics, Mundibiopharma, PathomIQ, Cadila Pharmaceuticals, and Arxeon during the conduct of the study. E. Stringer-Reasor reports other support from Pfizer, as well as personal fees and other support from Lilly, Novartis, Immunomedics, and Mylan during the conduct of the study; E. Stringer-Reasor also reports grants from Susan G Komen and VFoundation. N. Lakhani reports other support form Pfizer during the conduct of the study. N. Lakhani also reports other support from ALX Therapeutics, Ascentage, Asana, BeiGene, Constellation Pharma,
Funding Information:
Alexion, Cerulean, Forty Seven, Macrogenics, Merck, Shattuck Labs, Regeneron, TaiRx, Apexian, Formation Biologics (forbius), Symphogen, CytomX, InhibRx, Incyte, Jounce, Livzon, Northern Biologics, Innovent Biologics, Ikena, Odonate, Alpine Immune Sciences, Celgene, Seagen, and Mersana, as well as personal fees from Innovent Biologics outside the submitted work. A.R. Moreau is an employee of and owns stock in Pfizer Inc. D. Xuan was an employee of and owned stock in Pfizer Inc. at the time of this study. R. Li is an employee of and owns stock in Pfizer Inc. E.L. Powell is an employee of and owns stock in Pfizer Inc. A. Jackson-Fisher is an employee of and owns stock in Pfizer Inc. M. Bowers is an employee of and owns stock in Pfizer Inc. S. Alekar is an employee and owns stock in Pfizer Inc. X. Xin was an employee of and owned stock in Pfizer Inc. at the time this investigational work was being conducted. A.W. Tolcher reports personal fees and other support from Pfizer during the conduct of the study, as well as personal fees and other support from AbbVie, Agenus Inc, Asana Biosciences, Ascentage, AxImmune, Bayer, Gilde Healthcare Partners, HBM Partners, Immunomet Therapeutics Inc., Karma Oncology B.V., Mekanistic Therapeutics, Menarini Ricerche, Mersana, Nanobiotix, Partner Therapeutics, Pfizer Inc., Pierre Fabre, Ryvu Therapeutics, Seattle Genetics, Sioto Biotechnology Co., Spirea Limited Inc., Transcenta Therapeutics Inc., Trillium Therapeutics Inc., Mirati, Zymeworks Biopharmaceuticals Inc., Pyxis Oncology, Pieris Pharma, Pelican, NBE Therapeutics, Immunome, EMD Serono/Merck KGaA, Elucida, Eleven Bio, Deka Biosciences, Boehringer Ingelheim International GmbH, BioInvent, Aro Biotherapeutics, Adagene Inc., ABL Bio Inc., ADC Therapeutics SA, Aminex Therapeutics Inc., Amphivena Therapeutics Inc., Apros Therapeutics Inc., Arcellx Inc., Armo Biosciences, Arrys Therapeutics Inc., Artios Pharma Limited, Astex Pharmaceuticals, Basilea Pharmaceutica International Ltd, BioInvent International AB, BioNTech RNA Pharmaceuticals GmbH, Birdie Biopharmaceuticals, HK Ltd, BJ Bioscience Inc., Boston Biomedical Inc., Calgent Biotechnology Co. Ltd., Codiak Sciences Inc., CStone Pharmaceuticals (Suzhou) Co. Ltd., Cybrexa Therapeutics Inc., Daiichi Sankyo Inc., Deciphera Pharmaceuticals LLC, eFFECTOR Therapeutics Inc., Eli Lilly and Company, Gilead Sciences Inc., GlaxoSmithKline Research & Development Limited, Haihe Biopharma Co. Ltd., Shanghai Huaota, Heat Biologics, Ideaya Biosciences, ImmuneOncia Therapeutics Inc., IMPACT Therapeutics Inc., Inhibrx Inc., Innate Pharma SA, Janssen Research & Development, K-Group Beta Inc., KeChow Pharma Inc., Kiromic Biopharma Inc, Mabspace Biosciences (Suzhou) Co. Ltd., Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., NatureWise Biotech & Medicals Corporation, Navire Pharma Inc., Kirovax, MV Pharmaceuticals, 3’s Bio, NextCure Inc, Nitto BioPharma Inc., Odonate Therapeutics Inc., Oric Pharmaceuticals, Pelican Therapeutics Inc., Petra Pharma, Pieris Pharmaceuticals Inc., PMV Pharmaceuticals Inc., Qilu Puget Sound Biotherapeutics Corporation, Samumed LLC, Seattle Genetics Inc., Spring Bank Pharmaceuticals Inc., Sunshine Guojian Pharmaceutical (Shanghai) Co. Ltd., Symphogen A/S, Syndax Pharmaceuticals Inc., Synthorx Inc., Takeda, Tizona Therapeutics, and Zymeworks Inc. outside the submitted work. E. Calvo reports non-financial support and other support from Adcendo, Amcure, Janssen, T-knife, Chugai Pharmaceuticals, and PsiOxus Pharmaceuticals; personal fees and other support from Alkermes, Amunix, Anaveon, AstraZeneca, BMS, MSD, Nanobiotix, Novartis, OncoDNA, PharmaMar, Roche/ Genentech, Servier, and TargImmune; and grants from Achilles and BeiGene outside
Funding Information:
The study was approved by the institutional review board or independent ethics committee of the participating institutions and followed the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice (ICH GCP) guidelines. The patient informed consent complied with ICH GCP guidelines, local regulatory requirements, and legal requirements. The study was sponsored by Pfizer and registered at ClinicalTrials. gov (NCT02222922).
Publisher Copyright:
© 2021 The Authors; Published by the American Association for Cancer Research
PY - 2021/8/15
Y1 - 2021/8/15
N2 - Purpose: We investigated safety, tolerability, pharmacokinetics, and antitumor activity of the protein tyrosine kinase 7 (PTK7)targeted, auristatin-based antibody-drug conjugate (ADC) PF-06647020/cofetuzumab pelidotin (NCT02222922). Patients and Methods: Patients received PF-06647020 intravenously every 3 weeks at 0.2-3.7 mg/kg or every 2 weeks at 2.1-3.2 mg/kg, in sequential dose escalation, following a modified toxicity probability interval method. In dose expansion, pretreated patients with advanced, platinum-resistant ovarian cancer, non-small cell lung cancer (NSCLC), or triple-negative breast cancer (TNBC) received PF-06647020 2.8 mg/kg every 3 weeks. Results: The most common, treatment-related adverse events for PF-06647020 administered every 3 weeks were nausea, alopecia, fatigue, headache, neutropenia, and vomiting (45%-25%); 25% of patients had grade ≥ 3 neutropenia. Two patients experienced dose-limiting toxicities (grade 3 headache and fatigue) at the highest every 3 weeks dose evaluated. The recommended phase II dose was 2.8 mg/kg every 3 weeks. The overall safety profile observed with PF-06647020 administered every 2 weeks was similar to that of the every 3 weeks regimen. Systemic exposure for the ADC and total antibody generally increased in a dose-proportional manner. Antitumor activity was observed in treated patients with overall objective response rates of 27% in ovarian cancer (n = 63), 19% in NSCLC (n = 31), and 21% in TNBC (n = 29). Responders tended to have moderate or high PTK7 tumor expression by IHC. Conclusions: This PTK7-targeted ADC demonstrated therapeutic activity in previously treated patients with ovarian cancer, NSCLC, and TNBC at a dose range of 2.1-3.2 mg/kg, supporting further clinical evaluation to refine dose, schedule, and predictive tissue biomarker testing in patients with advanced malignancies.
AB - Purpose: We investigated safety, tolerability, pharmacokinetics, and antitumor activity of the protein tyrosine kinase 7 (PTK7)targeted, auristatin-based antibody-drug conjugate (ADC) PF-06647020/cofetuzumab pelidotin (NCT02222922). Patients and Methods: Patients received PF-06647020 intravenously every 3 weeks at 0.2-3.7 mg/kg or every 2 weeks at 2.1-3.2 mg/kg, in sequential dose escalation, following a modified toxicity probability interval method. In dose expansion, pretreated patients with advanced, platinum-resistant ovarian cancer, non-small cell lung cancer (NSCLC), or triple-negative breast cancer (TNBC) received PF-06647020 2.8 mg/kg every 3 weeks. Results: The most common, treatment-related adverse events for PF-06647020 administered every 3 weeks were nausea, alopecia, fatigue, headache, neutropenia, and vomiting (45%-25%); 25% of patients had grade ≥ 3 neutropenia. Two patients experienced dose-limiting toxicities (grade 3 headache and fatigue) at the highest every 3 weeks dose evaluated. The recommended phase II dose was 2.8 mg/kg every 3 weeks. The overall safety profile observed with PF-06647020 administered every 2 weeks was similar to that of the every 3 weeks regimen. Systemic exposure for the ADC and total antibody generally increased in a dose-proportional manner. Antitumor activity was observed in treated patients with overall objective response rates of 27% in ovarian cancer (n = 63), 19% in NSCLC (n = 31), and 21% in TNBC (n = 29). Responders tended to have moderate or high PTK7 tumor expression by IHC. Conclusions: This PTK7-targeted ADC demonstrated therapeutic activity in previously treated patients with ovarian cancer, NSCLC, and TNBC at a dose range of 2.1-3.2 mg/kg, supporting further clinical evaluation to refine dose, schedule, and predictive tissue biomarker testing in patients with advanced malignancies.
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U2 - 10.1158/1078-0432.CCR-20-3757
DO - 10.1158/1078-0432.CCR-20-3757
M3 - Article
C2 - 34083232
AN - SCOPUS:85112633409
VL - 27
SP - 4511
EP - 4520
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 16
ER -