Surgery is the standard treatment for non-metastatic RCC. Unfortunately, pts with stage II or III RCC have high risk of relapse with 5-year survival rates of 20% to 53%; prevention of recurrence is an unmet need. In CheckMate 214, the nivolumab + ipilimumab treatment combination demonstrated significant improvement in overall survival (OS) in first-line treatment of pts with advanced or metastatic RCC, with a manageable safety profile. This phase III multinational study will evaluate adjuvant nivolumab + ipilimumab vs placebo in pts with high risk of relapse after nephrectomy (NCT03138512).
Key inclusion criteria: Radical or partial nephrectomy with negative surgical margins >4 weeks and ≤12 weeks before randomization; predominantly clear primary tumor cell histology; pathologic TNM staging T2a (grade [G] 3 or 4), T2b (any G), T3 (any G), or T4 (any G) N0M0, or any T (any G) N1M0; Eastern Cooperative Oncology Group performance status ≤1, no clinical/radiological evidence of macroscopic residual disease or distant metastases post-nephrectomy, and tumor tissue obtained ≤3 months pre-enrollment. Key exclusion criteria: Pts with conditions requiring corticosteroid or immunosuppressive systemic treatment, autoimmune disease, prior treatment with drugs specifically targeting T-cell co-stimulation or checkpoint pathways, and prior systemic treatment for RCC. Pts are randomized 1:1 to receive nivolumab and ipilimumab at the specified dose on specified days for 24 weeks, or placebo infusions on the same schedule for 24 weeks or until recurrence, unacceptable toxicity, or withdrawal of consent. Stratification factors: TNM staging and type of nephrectomy procedure. Primary endpoint: Disease-free survival per blinded independent central review. Secondary endpoints: OS, safety, and tolerability. Tertiary/exploratory endpoints include disease-related symptoms based on the Functional Assessment of Cancer Therapy-Kidney Symptom Index, and changes in global health status based on EuroQoL’s EQ-5D-3L. Enrollment began July 2017 with a target of 800 pts.
Clinical trial identification
Legal entity responsible for the study
Bristol-Myers Squibb and Ono Pharmaceutical Company Limited.
Professional medical writing and editorial assistance were provided by Juan Sanchez-Cortes, PhD, and Lawrence Hargett of PPSI (a PAREXEL company), funded by Bristol-Myers Squibb.
A. Bex: Honoraria: Bristol-Myers Squibb, Pfizer, Roche, Eisai, Ipsen; Consulting or Advisory role: Bristol-Myers Squibb, Pfizer, Roche, Eisai, Ipsen; Research funding: Pfizer. V. Grünwald: Honoraria: Bristol-Myers Squibb; Consulting or Advisory role: Bristol-Myers Squibb, Novartis, Pfizer, Bayer; Speakers' bureaus: Bristol-Myers Squibb, Novartis, Pfizer. Y. Tomita: Honoraria: Pfizer, Novartis, Ono Pharmaceutical Co., Ltd.; Consulting or Advisory role: Ono Pharmaceutical Co., Ltd., Novartis, Taiho; Research funding (Inst): Takeda, Pfizer, Ono Pharmaceutical Co., Ltd., Astellas. E. Berghorn, M.B. McHenry: Employment: Bristol-Myers Squibb Stock or Other ownership: Bristol-Myers Squibb. R.J. Motzer: Consulting or Advisory role: Eisai, Exelixis, Genentech/Roche, Merck, Novartis, Pfizer; Research funding: Bristol-Myers Squibb, Eisai, Exelixis, Novartis, Pfizer. All other authors have declared no conflicts of interest.