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J Thorac Oncol. 2018 May;13(5):682-688. doi: 10.1016/j.jtho.2018.02.022. Epub 2018 Mar 6.

Phase 1/2 Study of the Safety and Tolerability of Nivolumab Plus Crizotinib for the First-Line Treatment of Anaplastic Lymphoma Kinase Translocation - Positive Advanced Non-Small Cell Lung Cancer (CheckMate 370).

Author information

1
Sarah Cannon Research Institute, Nashville, Tennessee. Electronic address: dspigel@tnonc.com.
2
Florida Cancer Specialists, Ocala, Florida.
3
OHC (Oncology Hematology Care), an affiliate of US Oncology Research, Cincinnati, Ohio; US Oncology Research, The Woodlands, Texas.
4
David Geffen School of Medicine at UCLA/Translational Research in Oncology-US Network, Santa Monica, California.
5
West Cancer Center, Memphis, Tennessee.
6
Fort Wayne Medical Oncology and Hematology, Fort Wayne, Indiana.
7
Minnesota Oncology, Minneapolis, Minnesota.
8
US Oncology Research, The Woodlands, Texas; Virginia Cancer Specialists, Fairfax, Virginia.
9
US Oncology Research, The Woodlands, Texas; Rocky Mountain Cancer Center, Denver, Colorado.
10
Bristol-Myers Squibb, Princeton, New Jersey.
11
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Abstract

INTRODUCTION:

Crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, is a first-line treatment for ALK translocation-positive advanced non-small cell lung cancer (NSCLC); however, patients eventually progress. Immunotherapies, including the programmed death-1 inhibitor nivolumab, have resulted in durable responses and long-term overall survival in patients with NSCLC. We hypothesized that combining targeted therapy with immunotherapy could result in more patients with responses and/or more durable responses. Herein we report data from a study assessing nivolumab plus crizotinib in patients with previously untreated advanced ALK translocation-positive NSCLC.

METHODS:

Group E in CheckMate 370 was a single-arm cohort designed to evaluate the safety of first-line nivolumab (240 mg every 2 weeks) plus crizotinib (250 mg twice daily) in patients with ALK translocation-positive NSCLC. The primary endpoint of safety would be met if ≤20% of patients discontinued treatment due to treatment-related adverse events by week 17. Objective response rate was a secondary endpoint. A planned safety review occurred in November 2016; the data cutoff was May 26, 2017.

RESULTS:

Of the first 13 patients treated with nivolumab plus crizotinib, 5 (38%) developed severe hepatic toxicities leading to the discontinuation of the combination. Of these, two patients died and the presence of severe hepatic toxicities may have contributed to death. Enrollment was closed and combination treatment discontinued due to observed grade ≥3 hepatic toxicities. Five patients (38%) had a partial response.

CONCLUSIONS:

These findings do not support further evaluation of nivolumab 240 mg every 2 weeks plus crizotinib 250 mg twice daily.

KEYWORDS:

Crizotinib; Nivolumab; Non–small cell lung cancer; PD-1 inhibitor; anaplastic lymphoma kinase translocation

PMID:
29518553
DOI:
10.1016/j.jtho.2018.02.022

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