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Clinical Trial ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.01256

Safety and Efficacy Results of a Phase I, Open-Label Study of Concurrent and Delayed Nivolumab in Combination With nab-Paclitaxel and Carboplatin in Advanced Non-Small Cell Lung Cancer

 Jonathan W. Goldman1, David M. Waterhouse2,  Ben George3, Peter J. O'Dwyer4, Rafia Bhore5, Sibabrata Banerjee5, Larry Lyons5, Chrystal U. Louis5, Teng J. Ong5 and  Karen Kelly6*
  • 1UCLA David Geffen School of Medicine, United States
  • 2Oncology Hematology Care, Inc., United States
  • 3Froedtert and the Medical College of Wisconsin, United States
  • 4Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, United States
  • 5Celgene (United States), United States
  • 6Comprehensive Cancer Center, University of California, Davis, United States

Introduction: Multicenter, phase I study of concurrent and delayed nivolumab plus nab-paclitaxel/carboplatin in advanced non-small cell lung cancer (NSCLC).
Methods: Chemotherapy-naive patients with advanced NSCLC (ineligible for potentially curative radiation or surgery) received nab-paclitaxel 100 mg/m2 (days 1, 8, 15) and carboplatin area under the curve 6 (day 1) intravenously every 21 days (first 4 cycles); nivolumab 5 mg/kg was administered intravenously (day 15) beginning in cycle 1 (concurrent) or cycle 3 (delayed) in separate cohorts and continued beyond the 4 chemotherapy cycles. The primary objective was to assess safety. Secondary objectives were to assess tolerability and explore antitumor activity.
Results: All 32 patients received chemotherapy; 20 of 22 and 6 of 10 patients also received concurrent or delayed nivolumab, respectively. No dose-limiting toxicities were reported in the concurrent cohort; 1 dose-limiting toxicity was reported in the delayed cohort. In the concurrent cohort, 20 patients (91%) had ≥1 grade 3/4 treatment-emergent adverse event (TEAE), and 7 (32%) discontinued treatment due to TEAEs. In the delayed cohort, all patients had ≥1 grade 3/4 TEAE, and 2 (20%) discontinued due to TEAEs. The median progression-free and overall survival, respectively, were 10.5 and 29.3 months in the concurrent cohort and 4.1 and 8.2 months in the delayed cohort.
Conclusions: The safety profile of the combination was consistent with that of individual agents and generally similar in the 2 cohorts. Efficacy outcomes in the concurrent cohort, but not in the delayed cohort, were encouraging and support the rationale for concurrent administration of nivolumab with nab-paclitaxel/carboplatin for the treatment of advanced NSCLC.

Keywords: Non-small cell lung cancer, Nab-Paclitaxel, Carboplatin, Nivolumab, Treatment beyond progression

Received: 07 Aug 2019; Accepted: 31 Oct 2019.

Copyright: © 2019 Goldman, Waterhouse, George, O'Dwyer, Bhore, Banerjee, Lyons, Louis, Ong and Kelly. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Karen Kelly, Comprehensive Cancer Center, University of California, Davis, Sacramento, 95817, California, United States,