A phase 1b study of cofetuzumab pelidotin monotherapy in patients with PTK7-expressing recurrent non-small cell lung cancer

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.