JTO Clinical and Research Reports (Nov 2021)

Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study

  • Jean-Louis Pujol, MD, PhD,
  • Johan Vansteenkiste, MD, PhD,
  • Luis Paz-Ares Rodríguez, MD, PhD,
  • Vanesa Gregorc, MD,
  • Julien Mazieres, MD, PhD,
  • Mark Awad, MD, PhD,
  • Pasi A. Jänne, MD, PhD,
  • Michael Chisamore, PhD,
  • Anwar M. Hossain, MStat,
  • Yanyun Chen, PhD,
  • J. Thaddeus Beck, MD, FACP

Journal volume & issue
Vol. 2, no. 11
p. 100234

Abstract

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Introduction: Abemaciclib is an oral, selective small-molecule CDK 4 and 6 inhibitor. In preclinical models, abemaciclib synergized with programmed cell death protein-1 blockade to enhance antitumor efficacy. Here, we report the safety and anticancer activity of abemaciclib plus pembrolizumab in two cohorts with NSCLC. Methods: This nonrandomized, open-label, phase 1b study included patients with previously untreated programmed death-ligand 1–positive, KRAS-mutant nonsquamous metastatic NSCLC (cohort A); squamous NSCLC after one previous platinum-containing chemotherapy regimen for metastatic disease (cohort B); and two breast cancer cohorts (disclosed separately). Patients received 150 mg abemaciclib every 12 hours plus 200 mg pembrolizumab intravenously on day 1 every 21 days. The primary objective was safety; secondary objectives included objective response rate, disease control rate, progression-free survival, and overall survival. Clinical Trial Number: NCT02779751. Results: Each cohort enrolled 25 patients. Grades greater than or equal to 3 treatment-emergent adverse events in cohorts A and B were reported by 20 (80%) and 19 patients (76%), respectively. Six patients in cohort A (24.0%) and two patients in cohort B (8.0%) had a confirmed partial response; disease control rate was 56% and 64%, respectively. Median progression-free survival was 7.6 months (95% confidence interval [CI]: 1.6–not estimable) and 3.3 months (95% CI: 1.4–5.2); median overall survival was 27.8 months (95% CI: 9.9–not estimable) and 6.0 months (95% CI: 3.7–13.1) in cohorts A and B, respectively. Conclusions: The combination of abemaciclib and pembrolizumab in stage IV NSCLC resulted in greater toxicity compared with that previously reported for each individual treatment. Risk-benefit profile does not warrant further evaluation of the combination in this population.

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