PUL01.02 AcceleRET Lung: A Phase 3 Study of First-Line Pralsetinib in Patients with RET-Fusion+ Advanced/Metastatic NSCLC

Abstract

RET gene fusions have been identified as oncogenic drivers in multiple tumor types, including 1–2% of non-small cell lung cancer (NSCLC). The investigational oral RET inhibitor, pralsetinib, potently and selectively targets oncogenic RET alterations, including those that confer resistance to multi-kinase inhibitors. In the registration-enabling phase 1/2 study (ARROW; NCT03037385), patients with RET-fusion+ NSCLC treated with pralsetinib 400 mg once daily (QD) after platinum-based chemotherapy (n=80) achieved an overall response rate (ORR) of 61% (95% CI 50, 72; two responses pending confirmation) per independent central review. In addition, an ORR of 73% (all centrally confirmed responses) was attained in the systemic treatment naïve cohort (n=26). Most treatment-related adverse events were grade 1–2 across the entire safety population treated with pralsetinib 400 mg QD (N=354). AcceleRET Lung, an international, open-label, randomized, phase 3 study, will evaluate the efficacy and safety of pralsetinib versus standard of care (SOC) in first-line treatment of advanced/metastatic RET fusion+ NSCLC (NCT04222972). This abstract was previously submitted to and presented at the American Society of Clinical Oncology 2020 annual meeting (May 29 to June 2, 2020). Approximately 250 patients with advanced/metastatic RET-fusion+ NSCLC will be randomized 1:1 to pralsetinib 400 mg QD or SOC (non-squamous histology: platinum/pemetrexed ± pembrolizumab followed by maintenance pemetrexed ± pembrolizumab; squamous histology: platinum/gemcitabine). Stratification factors include intended use of pembrolizumab, history of brain metastases, and Eastern Cooperative Oncology Group Performance Status 0 vs 1. Key eligibility criteria include no prior systemic treatment for advanced/metastatic NSCLC; RET-fusion+ tumor by local or central assessment, no additional actionable oncogenic drivers, no prior treatment with a selective RET inhibitor, and measurable disease per RECIST v1.1. Cross-over to receive pralsetinib upon disease progression will be permitted for patients randomized to SOC. The primary endpoint is progression-free survival (blinded independent central review; RECIST v1.1). Secondary endpoints include ORR, overall survival, duration of response, disease control rate, clinical benefit rate, time to intracranial progression, intracranial ORR, safety/tolerability, and quality of life. Recruitment has begun with sites (active or planned) in North America, Europe, Asia, and Australia.