A phase 2, fast real-time assessment of combination therapies in immuno-oncology trial in patients with advanced non-small cell lung cancer (FRACTION-lung)

Background

The unprecedented success of the immuno-oncology (I-O) agents, nivolumab and ipilimumab, in several malignancies has resulted in the rapid development of other I-O agents against novel immune targets. Given the potential promise of increased survival, these agents have not followed the traditional phase 2 trial evaluation. FRACTION-Lung is a randomized, open-label, phase 2 trial with an adaptive design that offers patients (pts) with advanced non-small cell lung cancer (NSCLC) expeditious access to early I-O therapies in combination with nivolumab. Based on both preclinical and clinical trial data, combinations of I-O therapies that have potential to produce transformational activity in lung cancer will be selected and offered to pts in a continuous throughput design.

Trial design

Methods: A master protocol defines the overarching framework for this clinical study in which pts with metastatic and/or recurrent NSCLC previously treated with platinum chemotherapy and tyrosine kinase inhibitors (if EGFR mutated or ALK rearranged) are eligible. Based on prior I-O therapy experience and PD-L1 expression, pts will be enrolled into various treatment tracks. Sub-protocols specify the preclinical and preliminary clinical data for new treatment combinations that will be added on a rolling basis. Pts will receive treatment until completion, progression, or toxicity. On progression, pts may enroll into other combination regimens allowing evolution of treatment if needed. An assessment of peripheral blood and tumor biomarkers will enable interrogation of the biological basis for pt response. Primary endpoints are objective response rate, duration of response, and progression-free survival at 24 weeks, with the potential for early stopping; the secondary endpoint is safety. The study is actively enrolling (NCT02750514).

Conclusion: FRACTION-Lung represents an innovative clinical trial that utilizes a rolling, adaptive design with novel I-O therapies. It will accelerate the development and selection of the next generation of transformational I-O combinations for pts with metastatic NSCLC.

Clinical trial identification

NCT02750514

Legal entity responsible for the study

Sponsored by Bristol Myers-Squibb

Funding

Sponsored by Bristol Myers-Squibb

Disclosure

P.M. Fracasso, D.J. Freeman, K. Simonsen, Y. Shen, A. Comprelli, J. Cassidy: Employee of Bristol-Myers Squibb. M. Gupta: Employed by the study sponsor (Bristol-Myers Squibb) and has stock ownership or options in Bristol-Myers Squibb. J.F. Gainor: Personal fees from Bristol-Myers Squibb, Novartis, Merck, Genentech/Roche, Clovis, Boehringher Ingelheim, and non-financial support from Jounce outside the submitted work. M. Hellmann: Consultant/Advisory Board member for BMS, Merck, Genentech, AZ, and Neon. Research support from BMS. L.Q. Chow: Fees from Astellas, grants, fees & non-financial support from Novartis, grants & fees from BMS, fees & non-financial support from Merck, grants from Eli Lilly/Imclone, OSI Pharma, Genentech, VentiRx, Pfizer, GSK, AZ/MedImmune outside the submitted work. P.M. Forde: Grants from BMS during the conduct of the study, and grants from BMS, Novartis, AstraZeneca, and Kyowa outside the submitted work. R. Govindan: Personal fees from Boehringer Ingelheim, GlaxoSmithKline, Celgene, Roche, Merck, Bayer, Genentech, Clovis Oncology, Helsinn Healthcare, and Pacritinib outside the submitted work. T.P. Reilly: Employee and stockholder of Bristol-Myers Squibb.