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Survival, safety, and response duration results of nivolumab (Anti-PD-1; BMS-936558; ONO-4538) in a phase I trial in patients with previously treated metastatic renal cell carcinoma (mRCC): Long-term patient follow-up.
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2013
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Mrcc CohortsImmune RegulationImmunologyPharmacotherapyImmunotherapeuticsImmunotherapyTumor ImmunologyOncologyGenitourinary CancerTumor ImmunityMrcc PtsRadiation OncologyT Cell ImmunityCancer TreatmentPharmacologyImmune Checkpoint ReceptorResponse Duration ResultsUrologyCancer ImmunosurveillanceImmune Checkpoint InhibitorMedicineLong-term Patient Follow-up
4514 Background: Programmed death-1 (PD-1) is an immune checkpoint receptor that negatively regulates T-cell activation. PD-L1, a PD-1 ligand, has been associated with poor prognosis in mRCC pts. In a phase I study of nivolumab, a PD-1 receptor blocking antibody, in pts with previously treated mRCC and other solid tumors, an MTD was not reached at 10 mg/kg IV Q2WK. Cohorts of mRCC pts were expanded at the 1 and 10 mg/kg dose levels. Methods: Pts received nivolumab for ≤12 cycles (4 doses/cycle) until unacceptable toxicity, progression, or complete response. We report overall survival (OS), updated response data, and long-term safety for the mRCC cohorts from a data analysis in July 2012. Results: 34 pts with mRCC were treated at 1 mg/kg (n=18) or 10 mg/kg (n=16). 44% of pts had received ≥3 prior therapies (74% prior antiangiogenic therapy; 59% prior immunotherapy). Median OS across doses has not yet been reached. Median duration of response was 12.9 months for both doses with 5 of the 10 responses lasting ≥1 year. The incidence of grade 3-4 related adverse events for the RCC cohort was 21% and included hypophosphatemia (6%) and respiratory disorders (6%), with no confirmed-drug related deaths or grade 3 pneumonitis. Treatment discontinuation due to drug-related AEs occurred in 18/304 (6%) of patients in the overall treated population. Conclusions: Nivolumab produced durable survival and responses in a subset of heavily pretreated mRCC pts, with an acceptable safety profile, even after long term continuous dosing. Overall survival appears promising for this population of pts. These findings provide the basis for an ongoing randomized phase III trial of nivolumab in mRCC (NCT01668784). Follow-up data through a February 2013 cutoff is being collected. Clinical trial information: NCT00730639. [Table: see text]