Nivolumab is a PD-1 inhibitor that has demonstrated durable responses and improved survival in patients (pts) with previously treated, metastatic non-small-cell lung cancer (NSCLC). This is the first report of neoadjuvant PD-1 blockade in pts with early stage NSCLC.
Pts with untreated, resectable, stage I-IIIA NSCLC underwent pretreatment tumor biopsy and then received two doses of nivolumab 3mg/kg administered at 4 and 2 weeks prior to surgical resection. Postoperatively, standard adjuvant chemotherapy was administered at investigator discretion. The primary endpoints were safety and feasibility of preoperative nivolumab administration. Exploratory endpoints included the degree of pathologic regression, as well as molecular and immunophenotypic changes in tumor and peripheral blood, including T cell repertoire analysis by TCR CDR3 deep sequencing, function, gene expression profiling, and tumor antigen recognition. An initial 6-patient safety run-in cohort was followed by an expansion cohort, with a planned accrual of 16 resected pts.
As of 09/19/2016, 18 pts were enrolled and 16 completed surgical resection (two patients were not ultimately resected). No delays to surgery or surgical complications related to nivolumab occurred. Twelve of 15 resected patients (80%) had pathologic evidence of tumor regression, and 6 (40%) achieved major pathologic responses (MPR;
Neoadjuvant nivolumab was feasible and safe. Most pts have pathologic evidence of anti-tumor response, including MPR in 6 of 15 pts. Neoadjuvant anti-PD1 immunotherapy may have substantial anti-tumor activity in early stage NSCLC.
Clinical trial identification
Legal entity responsible for the study
Johns Hopkins University School of Medicine
Stand Up to Cancer, AACR, CRI and LUNGevity BMS pharmaceuticals supplied nivolumab and funding for PD-L1 testing
P.M. Forde: Research grants to my institution for clinical trials of which I am PI from BMS, Novartis, AstraZeneca, Kyowa, outside of this submitted work. Consultant/Advisory Board (uncompensated) - AstraZeneca, Celgene. J.E. Chaft: Consulting or Advisory Role: Myriad Genetics, Biodesix, Genentech/Roche, Clovis Oncology, AstraZeneca/MedImmune. Honoraria: Dava Oncology Research funding to Institution: Lilly, Genentech/Roche, BMS, AstraZeneca/Medimmune. M. Hellmann: Consulting or Advisory Role: Third Rock Ventures, BMS, Merck, Genentech, Alexion Pharmaceuticals, Inovio Pharmaceuticals, AstraZeneca/Medimmune Research Funding: BMS J.D. Wolchok: Consultant/Advisory Role: BMS, Merck, Medimmune, Ziopharm, Polynoma, Polaris, Jounce, Genentech Travel/Expenses: BMS Stock/Ownership: Potenza, Vesuvius Research Funding to Institution: BMS, Medimmune, GSK, Merck. E. Gabrielson: Leadership: Taxus Cardium Pharmaceuticals Stock/Ownership: Taxus Cardium Pharmaceuticals. J.M. Taube: Consultant/advisory board for Merck, BMS, Astra Zeneca and I receive investigator-initiated research funding from BMS. V.E. Velculescu: Leadership/Stock/Ownership/Consultant/Advisory Role: Personal Genome Diagnostics Honoraria: Janssen Patents/Royalties: Qiagen, Exact Sciences, Inostics, Myriad Genetics, Personal Genome Diagnostics. S.L. Topalian: Consultant/Advisory Role: Five Prime Therapeutics, GSK, Jounce Therapeutics, ImaginAb Travel Expenses: BMS, Five Prime Stock/Ownership: Five Prime Research Funding: BMS. D.M. Pardoll: Consultant/Advisory Role: Pfizer Research Funding: Potenza Therapeutics, Compugen, BMS Patents/Royalties: BMS Travel/Expenses: AstraZeneca, BMS, Pfizer. J.R. Brahmer: Consultant/Advisory Role: Merck KGaA, BMS, Lilly Travel Expenses: BMS, Merck Other relationship: BMS Research Funding to Institution: BMS, Merck, AstraZeneca, Celgene. All other authors have declared no conflicts of interest.