Ipilimumab plus nivolumab and chemoradiotherapy followed by surgery in patients with resectable and borderline resectable T3-4N0-1 non-small cell lung cancer: the INCREASE trial
- PMID: 32795284
- PMCID: PMC7427738
- DOI: 10.1186/s12885-020-07263-9
Ipilimumab plus nivolumab and chemoradiotherapy followed by surgery in patients with resectable and borderline resectable T3-4N0-1 non-small cell lung cancer: the INCREASE trial
Abstract
Background: The likelihood of a tumor recurrence in patients with T3-4N0-1 non-small cell lung cancer following multimodality treatment remains substantial, mainly due distant metastases. As pathological complete responses (pCR) in resected specimens are seen in only a minority (28-38%) of patients following chemoradiotherapy, we designed the INCREASE trial (EudraCT-Number: 2019-003454-83; Netherlands Trial Register number: NL8435) to assess if pCR rates could be further improved by adding short course immunotherapy to induction chemoradiotherapy. Translational studies will correlate changes in loco-regional and systemic immune status with patterns of recurrence.
Methods/design: This single-arm, prospective phase II trial will enroll 29 patients with either resectable, or borderline resectable, T3-4N0-1 NSCLC. The protocol was approved by the institutional ethics committee. Study enrollment commenced in February 2020. On day 1 of guideline-recommended concurrent chemoradiotherapy (CRT), ipilimumab (IPI, 1 mg/kg IV) and nivolumab (NIVO, 360 mg flat dose IV) will be administered, followed by nivolumab (360 mg flat dose IV) after 3 weeks. Radiotherapy consists of once-daily doses of 2 Gy to a total of 50 Gy, and chemotherapy will consist of a platinum-doublet. An anatomical pulmonary resection is planned 6 weeks after the last day of radiotherapy. The primary study objective is to establish the safety of adding IPI/NIVO to pre-operative CRT, and its impact on pathological tumor response. Secondary objectives are to assess the impact of adding IPI/NIVO to CRT on disease free and overall survival. Exploratory objectives are to characterize tumor inflammation and the immune contexture in the tumor and tumor-draining lymph nodes (TDLN), and to explore the effects of IPI/NIVO and CRT and surgery on distribution and phenotype of peripheral blood immune subsets.
Discussion: The INCREASE trial will evaluate the safety and local efficacy of a combination of 4 modalities in patients with resectable, T3-4N0-1 NSCLC. Translational research will investigate the mechanisms of action and drug related adverse events.
Trial registration: Netherlands Trial Registration (NTR): NL8435 , Registered 03 March 2020.
Keywords: Locally advanced; NSCLC; Neoadjuvant immunotherapy; Pathological response; Thoracic surgery.
Conflict of interest statement
CD, FS, JV, SH, JD, MF, DH, PV, IHB, LM, JGV and DOLdeclare no competing interests. TG receives consultation fees from TILT Biotherapeutics, DCPrime, Macrophage Pharma and Partner Therapeutics, and receives research support from Marcrophage Pharma and Idera Pharmaceuticals, outside the submitted work. TR reports research support from Abbvie Pharmaceuticals ad participates in advisory boards of Roche, MSD, and Abbvie. Suresh Senan reports consulting/advisory fees from AstraZeneca, Merck, Celgene and Eli Lilly. His department has received research funding from AstraZeneca, ViewRay Inc. and Varian, outside the submitted work. IB reports consulting/advisory fees from AstraZeneca, MSD, Boehringer Ingelheim, Pfizer, Takeda, Celgene, Roche, BMS and Eli Lilly. His department has received research funding from AstraZeneca, BMS, Boehringer Ingelheim, HeatBiologics, Roche and MSD outside the submitted work.
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