The proposed study will evaluate the safety and feasibility of preoperative administration nivolumab +/- ipilimumab in patients with high-risk resectable NSCLC, and will facilitate a comprehensive exploratory characterization of the tumor immune milieu and circulating immune cells and soluble factors in these patients. Data obtained in this study will provide valuable information for planning further prospective clinical trials of anti-PD-1 and other immunotherapies in NSCLC, both in the peri-operative and advanced disease setting.
The proposed study will evaluate the safety and feasibility of preoperative administration nivolumab +/- ipilimumab in patients with high-risk resectable NSCLC, and will facilitate a comprehensive exploratory characterization of the tumor immune milieu and circulating immune cells and soluble factors in these patients. Data obtained in this study will provide valuable information for planning further prospective clinical trials of anti-PD-1 and other immunotherapies in NSCLC, both in the peri-operative and advanced disease setting. Ultimately, it is highly desirable to discover prospective biomarkers of response and toxicity to allow patients with NSCLC who are most likely to derive benefit to receive anti-PD-1 treatment, and conversely to minimize the risk of toxicity and ineffective treatment for patients who are unlikely to benefit. In addition, an amendment to this study allows evaluation of the combination of nivolumab and the anti-CTLA4 antibody, ipilimumab in the neoadjuvant setting for the treatment of resectable NSCLC. In a large, multicohort, phase 1 trial, the ORR to combination ipilimumab and nivolumab therapy in patients unselected by PD-L1 status ranged from 39-47%. Incidence of grade 3-4 toxicity ranged from 33-37% across the combination ipilimumab and nivolumab cohorts which compares favorably with the rates of toxicity due to platinum doublet chemotherapy in this disease setting. The current amendment includes addition of a third arm (Arm C) combining nivolumab and platinum-doublet chemotherapy in the neoadjuvant setting.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
39
Anti-PD-1 Therapy
Anti-PD-1 Therapy
Anti-PD-1 Therapy
Anti-PD-1 Therapy
Johns Hopkins at Bayview Medical Center
Baltimore, Maryland, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Memorial Sloan Kettering
New York, New York, United States
Swedish Cancer Insitute
Edmonds, Washington, United States
Johnathan Spicer
Montreal, Quebec, Canada
Safety as Measured by Number of Participants With Grade 3 and 4 Lab Abnormalities, as Defined by CTCAE v4.03
Safety will be measured by drawing safety labs. (CBC and a Chemistry Panel will be drawn at 2 week intervals during Nivolumab administration). Grade 3 and 4 lab abnormalities will be recorded from both participating sites.
Time frame: 8 weeks
Safety as Assessed by Number of Grade 3 and 4 Adverse Events
Number of Grade 3 and 4 adverse events as defined by CTCAE v4.03 that occur while a subject is participating in the study.
Time frame: 8 weeks
Pathologic Response
Pathologic response to neoadjuvant nivolumab, nivolumab plus ipilimumab, and nicvolumab, carboplatin, and paclitaxel in resected tumor and lymph nodes. The rate of major pathologic response, defined as \<10% residual viable tumor cells in the resection specimen will be compared to historic data with neoadjuvant chemotherapy.
Time frame: 6 weeks
Radiographic Response
Radiographic response to neoadjuvant nivolumab, nivolumab plus ipilimumab, and carboplatin and paclitaxel as defined by RECIST 1.1.
Time frame: 5 weeks
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