Abemaciclib, an oral inhibitor of CDK 4/6, and pembrolizumab both have demonstrated single-agent activity and acceptable safety profiles with nonoverlapping toxicities. This ongoing open-label phase 2 study (JPCE) is evaluating the safety and preliminary efficacy of abemaciclib (150 mg orally every 12 hours) on a continuous schedule for 21 days combined with pembrolizumab (200 mg IV every 21 days). Enrolled patients will be categorized into 1 of 3 disease cohorts: [A] KRAS muted, PD-L1–positive, metastatic non–small-cell lung cancer (NSCLC); [B] metastatic NSCLC with squamous histology; and [C] hormone receptor–positive, HER2-negative metastatic breast cancer. The total accrual will be approximately 75 patients; 25 per cohort.
Patients with NSCLC who are eligible for cohort A require a confirmed KRAS mutation, and PD-L1 expression ≥1%. They cannot have received chemotherapy for metastatic NSCLC. Cohort B includes patients with predominantly squamous NSCLC who received 1 prior platinum-based chemotherapy for advanced NSCLC. Patients must have measurable disease, adequate organ function, an ECOG PS ≤1, and a life expectancy that exceeds 12 weeks.
The primary objective of the study is to characterize the safety profile of abemaciclib plus pembrolizumab in NSCLC. Secondary objectives include objective response rate, disease control rate, duration of response, progression-free survival, characterization of pharmacokinetics, and health outcomes using the MD Anderson Symptom Inventory.
An interim analysis of safety and preliminary efficacy may occur after all patients have completed (or discontinued from) approximately 24 weeks of treatment. The final overall survival analysis will occur based on data collected for approximately 12 months after the last patient receives treatment.
This phase 2 trial is expected to report primary outcome data in late 2017 or early 2018.
Mazieres M, et al. WCLC 2016. Abstract P2 06.012. ID 4176.