11 Long-Term Follow-Up from the OMNIVORE Trial: Response-Adaptive Nivolumab and Ipilimumab in Advanced Renal Cell Carcinoma (NCT03652142)

Background Immune checkpoint inhibitor-based combinations represent the standard of care for advanced renal cell carcinoma (RCC). The OMNIVORE trial (NCT03652142) investigated a response-adaptive strategy including treatment discontinuation in early nivolumab responders (Arm A) and salvage ipilimumab addition in non-responders (Arm B). We present long-term outcomes from OMNIVORE with approximately 6 years follow up in Arm A and 2.5 years follow up in Arm B. Methods OMNIVORE was a multi-center investigator-initiated phase II trial in which patients with unresectable, locally recurrent, or metastatic RCC received induction nivolumab monotherapy. Patients achieving a confirmed objective response discontinued nivolumab and entered observation (Arm A), while patients with stable disease or progressive disease received two doses of ipilimumab added to ongoing nivolumab (Arm B). The primary endpoints were the proportion of patients with durable CR/PR at 1 year after nivolumab discontinuation (arm A) and proportion with SD/PD receiving nivolumab who converted to PR/CR after the addition of ipilimumab (arm B). Secondary endpoints included overall survival, treatment-free interval, duration of disease control, progression-free survival (PFS), and toxicity. This analysis characterizes long-term overall survival across the full study cohort and durability of response among patients who discontinued nivolumab following an early objective response. Results Of 83 patients who initiated treatment, 12 (14%) were allocated to Arm A, 57 (69%) were allocated to Arm B, and 14 (17%) were not allocated due to progressive disease or death. The median follow-up among living patients was 59.4 months (range 29.1 to 85.4 months) in Arm A and 31.4 months (range 4.6-62.6 months) in Arm B. The 3-year overall survival rate from nivolumab initiation was 64% (95% CI 51%-74%) in the overall cohort, 83% (95% CI 48%-96%) in Arm A, and 63% (95% CI 47%-76%) in Arm B. Of the 12 Arm A patients, 6 (50%) remained off nivolumab in durable partial or complete response at 1 year following treatment discontinuation, of whom 5 maintained responses beyond 43 months off therapy with all remaining alive at last known follow-up with overall survival ranging from 48.8 to 85.4 months. Of the 6 patients in Arm A who experienced disease progression and resumed treatment, only 1 achieved a durable complete response, and remains on treatment at 83.2 months from nivolumab initiation. All 57 Arm B patients received 2 doses of ipilimumab with maintenance nivolumab for a median treatment duration of 3.7 months (range 1-24.8 months). At the time of last data cutoff, the ORR was 4% (90% CI, 1% to 11%) and median progression-free survival from nivolumab plus ipilimumab initiation was 4.6 months (95% CI 2.7-6.5 months). Conclusions With extended follow-up, the results of OMNIVORE demonstrate that a meaningful subset of patients with metastatic ccRCC who experience early objective response to anti-PD1 may discontinue therapy and sustain prolonged treatment free benefit. Whereas, ccRCC patients who did not experience early objective response to anti-PD1 did not benefit from subsequent treatment with ipilimumab and nivolumab. Correlative studies are underway to identify biomarkers of extreme response to treatment.