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

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

Abstract

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.

Keywords: Abemaciclib; KRAS-mutant; PD-L1 positive non–small cell lung cancer; Pembrolizumab; Squamous.

© 2021 THE AUTHORS.

Figures

Figure 1
Figure 1
Best percentage change in tumor size from baseline according to RECIST version 1.1. Best percentage change in tumor size from baseline is presented for the safety populations in (A) cohort A and (B) cohort B. The PD-L1 TPS in cohort A was evaluated by an IHC assay in tumor tissue samples (see the Materials and Methods section). Strong PD-L1 TPS was greater than or equal to 50%, and weak PD-L1 TPS was 1% to 49%. Best overall responses presented here are confirmed responses. Note: Patients without any postbaseline data are not included in the graphs. aThe patient did not meet stable disease criteria. IHC, immunohistochemistry; PD-L1, programmed death-ligand 1; RECIST, Response Evaluation Criteria In Solid Tumors; TPS, tumor proportion score.

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