BACKGROUND: Protein tyrosine kinase 7 (PTK7) overexpression in lung cancer is associated with tumor progression. Cofetuzumab pelidotin (Cofe-P) is an antibody-drug conjugate comprising an anti-PTK7 antibody conjugated to a microtubule inhibitor. Herein, we report the results of a phase 1b study evaluating Cofe-P safety, efficacy, and pharmacokinetics in patients with recurrent non-small cell lung cancer (NSCLC). METHODS: This signal-seeking phase 1b, open-label, multicenter, single-arm study enrolled patients with PTK7-expressing recurrent NSCLC. Cofe-P was administered at 2.8 mg/kg intravenously once every 3 weeks. The primary endpoint was objective response rate (ORR) and secondary endpoints were duration of response (DOR), progression-free survival (PFS), and overall survival (OS). RESULTS: Overall, 65 patients received Cofe-P
51 had PTK7 expression of ≥90 % tumor cells with ≥2+ staining intensity by immunohistochemistry. All patients reported adverse events (AEs), most commonly alopecia (52 %) and decreased neutrophil count (43 %)
69 % had grade ≥3 AEs, including grade ≥3 neutropenia in 25 %. Treatment-related AEs were reported in 94 % of patients
none were fatal. Overall, ORR was 18 %
in patients with PTK7 expression of ≥90 % tumor cells with ≥2+ staining and non-squamous epidermal growth factor receptor (EGFR) wild type or mutant, or squamous NSCLC, ORR was 21 %, 15 %, and 13 %, respectively. Overall, median DOR was 7.2 months, median PFS was 5.5 months, and median OS was 12.6 months
longest DOR (median 9.0 months), PFS (median 6.8 months), and OS (median 12.6 months) were in patients with non-squamous EGFR-mutant NSCLC. CONCLUSIONS: Cofe-P demonstrated a manageable safety profile and preliminary efficacy across NSCLC histologies and EGFR mutation status. These data support PTK7 as a valid therapeutic target for NSCLC.