First-in-Human Study of PF-06647020 (Cofetuzumab Pelidotin), an Antibody–Drug Conjugate Targeting Protein Tyrosine Kinase 7, in Advanced Solid Tumors

• Published in: Clinical cancer research Vol. 27; no. 16; pp. 4511 - 4520
• Main Authors: Maitland, Michael L., Sachdev, Jasgit C., Sharma, Manish R., Moreno, Victor, Boni, Valentina, Kummar, Shivaani, Stringer-Reasor, Erica, Lakhani, Nehal, Moreau, Allison R., Xuan, Dawei, Li, Ray, Powell, Eric L., Jackson-Fisher, Amy, Bowers, Michelle, Alekar, Shilpa, Xin, Xiaohua, Tolcher, Anthony W., Calvo, Emiliano
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 15.08.2021
• Subjects: Adult; Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Ovarian Epithelial - drug therapy; Carcinoma, Ovarian Epithelial - pathology; Cell Adhesion Molecules - antagonists & inhibitors; Clinical Trials: Targeted Therapy; Female; Humans; Immunoconjugates - pharmacology; Immunoconjugates - therapeutic use; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Middle Aged; Neoplasm Staging; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Receptor Protein-Tyrosine Kinases - antagonists & inhibitors; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - pathology
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-20-3757

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 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. 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 ( = 63), 19% in NSCLC ( = 31), and 21% in TNBC ( = 29). Responders tended to have moderate or high PTK7 tumor expression by IHC. 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.