Phase (Ph) 3 Study of Patritumab (P) Plus Erlotinib (E) in Egfr Wild-Type Subjects with Advanced Non–Small Cell Lung Cancer (Nsclc)

Abstract

Background: P is a fully human anti-human epidermal growth factor receptor 3 (HER3) antibody that inhibits HER3 from binding to its ligand, heregulin (HRG). A Ph 2 study (NCT01211483; von Pawel, ASCO 2014, #8045; Mendell, ASCO 2014, #e19016) demonstrated progression-free survival (PFS) benefits for subjects with advanced NSCLC and high HRG mRNA expression (HRG-high) when treated with P + E vs E.Trial design: This is a Ph 3, randomized, placebo-controlled, double-blind, multicenter study examining P + E vs E in EGFR wild-type subjects with advanced NSCLC who have progressed on 1–2 systemic therapies. The study has 2 parts: part A will enroll subjects with any HRG value to confirm Ph 2 results and further refine the HRG cutoff level before expanded enrollment in part B, while also evaluating the efficacy of P + E vs E in the HRG-high group; part B will enroll only HRG-high (per revised criteria) subjects to evaluate the efficacy and safety of P + E vs E. Subjects must have tumor samples (for HRG, and EGFR/anaplastic lymphoma kinase [ALK] measurements for adenocarcinoma histology), and must not have EGFR mutations, ALK rearrangement, or received prior anti-HER family treatment. Recruitment began April 2014, and 780 subjects will be recruited: 180 to part A (120 HRG-high, 60 HRG-low), 600 to part B (all HRG-high). Part A subjects will be stratified by histology subtype, ECOG status, and best response according to the most recent therapy. Part B subjects will be stratified similarly plus by geographic region and subcategories of HRG-high status. Within each stratum, subjects will be randomized in a 1:1 ratio to E (150 mg/day PO) with P (18 mg/kg IV loading dose, then 9 mg/kg maintenance dose every 3 weeks) or E with placebo. Subjects will be treated until disease progression, unacceptable toxicity, or withdrawal of consent. In part A, the primary end point is PFS; secondary end points are overall survival (OS), objective response rate (ORR), and safety. In Part B, the primary end point is OS; secondary end points are PFS, ORR, changes in quality of life, and safety. The study has 90% power to detect a 67% increase in median PFS in HRG-high subjects in part A (with 100 PFS events) and a 37% increase in median OS in part B (with 424 deaths).Disclosure: L. Paz-Ares: I have served on Advisory Boards for Daiichi; J. von Pawel: Advisory Boards for Daiichi Sankyo, Pfizer Inc., Vertex Pharmaceuticals, Novartis, Clovis, and AbbVie.; J. Mendell: Stock ownership and corporate-sponsored research from Daiichi Sankyo; X. Jin: Stock ownership in Daiichi Sankyo; C. Copigneaux: Employee of and holds stock ownership in Daiichi Sankyo; R. Beckman: Full-time employment and stock ownership in Daiichi Sankyo; stock ownership in Johnson & Johnson; Advisory Board for Cancer Institute of New Jersey Medicine. All other authors have declared no conflicts of interest.