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

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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Abemaciclib KRAS-mutant PD-L1 positive non–small cell lung cancer Pembrolizumab Squamous Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/c9caff189596499fa7e9767a030f2c97
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spelling	oai:doaj.org-article:c9caff189596499fa7e9767a030f2c972021-12-02T05:03:45ZAbemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study2666-364310.1016/j.jtocrr.2021.100234https://doaj.org/article/c9caff189596499fa7e9767a030f2c972021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S266636432100093Xhttps://doaj.org/toc/2666-3643Introduction: 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.Jean-Louis Pujol, MD, PhDJohan Vansteenkiste, MD, PhDLuis Paz-Ares Rodríguez, MD, PhDVanesa Gregorc, MDJulien Mazieres, MD, PhDMark Awad, MD, PhDPasi A. Jänne, MD, PhDMichael Chisamore, PhDAnwar M. Hossain, MStatYanyun Chen, PhDJ. Thaddeus Beck, MD, FACPElsevierarticleAbemaciclibKRAS-mutantPD-L1 positive non–small cell lung cancerPembrolizumabSquamousNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJTO Clinical and Research Reports, Vol 2, Iss 11, Pp 100234- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Abemaciclib KRAS-mutant PD-L1 positive non–small cell lung cancer Pembrolizumab Squamous Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Abemaciclib KRAS-mutant PD-L1 positive non–small cell lung cancer Pembrolizumab Squamous Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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 Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study
description	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.
format	article
author	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
author_facet	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
author_sort	Jean-Louis Pujol, MD, PhD
title	Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study
title_short	Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study
title_full	Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study
title_fullStr	Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study
title_full_unstemmed	Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study
title_sort	abemaciclib in combination with pembrolizumab for stage iv kras-mutant or squamous nsclc: a phase 1b study
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/c9caff189596499fa7e9767a030f2c97
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Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study

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