1. First-in-Human Study of PF-06647020 (Cofetuzumab Pelidotin), an Antibody-Drug Conjugate Targeting Protein Tyrosine Kinase 7, in Advanced Solid Tumors
- Author
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Dawei Xuan, Valentina Boni, Xiaohua Xin, Shilpa Alekar, Anthony W. Tolcher, Jasgit C. Sachdev, Nehal Lakhani, Victor Moreno, Ruifeng Li, Amy Jackson-Fisher, Erica Stringer-Reasor, Michael L. Maitland, Allison R Moreau, Shivaani Kummar, Michelle Bowers, Emiliano Calvo, Eric L. Powell, and Manish R. Sharma
- Subjects
Adult ,Cancer Research ,medicine.medical_specialty ,Immunoconjugates ,Lung Neoplasms ,Triple Negative Breast Neoplasms ,Neutropenia ,Carcinoma, Ovarian Epithelial ,Gastroenterology ,Breast cancer ,Pharmacokinetics ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,Adverse effect ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Ovarian Neoplasms ,business.industry ,Receptor Protein-Tyrosine Kinases ,Middle Aged ,medicine.disease ,Regimen ,Oncology ,Tolerability ,Toxicity ,Female ,business ,Ovarian cancer ,Cell Adhesion Molecules - Abstract
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.
- Published
- 2020