{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["27(16)"],"submitter":["Maitland ML"],"funding":["Pfizer"],"pubmed_abstract":["<h4>Purpose</h4>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).<h4>Patients and methods</h4>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.<h4>Results</h4>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 (<i>n</i> = 63), 19% in NSCLC (<i>n</i> = 31), and 21% in TNBC (<i>n</i> = 29). Responders tended to have moderate or high PTK7 tumor expression by IHC.<h4>Conclusions</h4>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."],"journal":["Clinical cancer research : an official journal of the American Association for Cancer Research"],"pagination":["4511-4520"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9401513"],"repository":["biostudies-literature"],"pubmed_title":["First-in-Human Study of PF-06647020 (Cofetuzumab Pelidotin), an Antibody-Drug Conjugate Targeting Protein Tyrosine Kinase 7, in Advanced Solid Tumors."],"pmcid":["PMC9401513"],"pubmed_authors":["Stringer-Reasor E","Xuan D","Jackson-Fisher A","Li R","Moreau AR","Alekar S","Maitland ML","Sharma MR","Boni V","Kummar S","Sachdev JC","Moreno V","Lakhani N","Tolcher AW","Xin X","Calvo E","Powell EL","Bowers M"],"additional_accession":[]},"is_claimable":false,"name":"First-in-Human Study of PF-06647020 (Cofetuzumab Pelidotin), an Antibody-Drug Conjugate Targeting Protein Tyrosine Kinase 7, in Advanced Solid Tumors.","description":"<h4>Purpose</h4>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).<h4>Patients and methods</h4>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.<h4>Results</h4>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 (<i>n</i> = 63), 19% in NSCLC (<i>n</i> = 31), and 21% in TNBC (<i>n</i> = 29). Responders tended to have moderate or high PTK7 tumor expression by IHC.<h4>Conclusions</h4>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.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Aug","modification":"2026-05-10T06:44:14.916Z","creation":"2025-04-04T13:08:41.25Z"},"accession":"S-EPMC9401513","cross_references":{"pubmed":["34083232"],"doi":["10.1158/1078-0432.CCR-20-3757"]}}