In the phase II OMNIVORE study reported in the Journal of Clinical Oncology, Rana R. McKay, MD, and colleagues did not find evidence supporting a strategy of discontinuing nivolumab monotherapy in responders and adding ipilimumab in nivolumab nonresponders among patients with metastatic renal cell carcinoma.
Rana R. McKay, MD
Study Details
The U.S.-based, multicenter, investigator-initiated trial enrolled 83 patients with metastatic renal cell carcinoma (96% clear cell histology, 51% treatment-naive) who had received no prior checkpoint inhibitor therapy between October 2017 and July 2019. All patients received nivolumab alone (initially at 240 mg every 2 weeks and then at 480 mg every 4 weeks after protocol amendment). Subsequent arm allocation was based on response; patients with partial or complete response within 6 months discontinued nivolumab and were observed (arm A). Patients with stable disease or progressive disease after no more than 6 months of nivolumab received two doses of ipilimumab (1 mg/kg every 3 weeks in combination with nivolumab 3 mg/kg every 3 weeks; arm B). The primary endpoints were the proportion of patients with objective response at 1 year after nivolumab discontinuation (arm A), and the proportion of nivolumab nonresponders who converted to partial or complete response after treatment with ipilimumab (arm B).
Key Findings
Of the 83 patients who initiated treatment, 69 underwent arm allocation; 14 did not undergo allocation due to progressive disease in 7 and toxicity in 7. Median follow-up was 19.5 months.
Within 6 months, nivolumab monotherapy resulted in confirmed partial response in 10 patients (12%) and conformed or unconfirmed partial response in 12 (14%).
“In this study, nivolumab followed by two doses of ipilimumab resulted in no complete responses and a low rate of conversion to partial response. The number of patients evaluated for nivolumab discontinuation was too small to assess the value of this approach. Currently, our data do not support a response-adaptive strategy for checkpoint blockade in advanced renal cell carcinoma.”— Rana R. McKay, MD, and colleagues
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Among the 12 patients allocated to arm A (discontinuation of nivolumab), 5 (42%) remained off nivolumab at ≥ 1 year. Four patients restarted nivolumab within 6 months after treatment discontinuation (3 due to progression; 1 still in partial response). Three patients who had not reached the 1-year mark were still in active follow-up at time of analysis.
Among 57 patients (69%) allocated to arm B (addition of ipilimumab), 2 patients (4%) converted to a confirmed partial response, with no complete responses observed.
Among all patients, median overall survival was not reached, with an 18-month rate of 79%.
The investigators concluded, “In this study, nivolumab followed by two doses of ipilimumab resulted in no complete responses and a low rate of conversion to partial response. The number of patients evaluated for nivolumab discontinuation was too small to assess the value of this approach. Currently, our data do not support a response-adaptive strategy for checkpoint blockade in advanced renal cell carcinoma.”
Toni K. Choueiri, MD, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bristol Myers Squibb. For full disclosures of the study authors, visit ascopubs.org.
