Adjuvant Nivolumab/Ipilimumab Fails to Meet DFS End Point in Localized RCC

The combination of nivolumab (Opdivo) and ipilimumab (Yervoy) failed to elicit a statistically significant improvement in disease-free survival (DFS) compared with placebo as adjuvant treatment in patients with localized renal cell carcinoma (RCC) who had undergone a full or partial removal of the kidney and were at moderate or high risk of relapse, failing to meet the primary end point of part A of the phase 3 CheckMate-914 trial (NCT03138512).¹

A full evaluation of the data will be published in the future.

“Even with notable progress in the treatment of metastatic RCC, there are still limited treatment options available for patients with localized disease,” said Dana Walker, MD, MSCE, the vice president and development program lead of Genitourinary Cancers at Bristol Myers Squibb, stated in a press release. “[Nivolumab] and [nivolumab]-based combinations have shown survival benefits in several earlier-stage and advanced cancers, including genitourinary tumors, and we are disappointed that the final analysis of CheckMate-914 part A did not show this same benefit for the post-surgical treatment of patients with localized RCC. Nonetheless, we are dedicated to continuing research and advancing cancer care for all patients with RCC.”

Nivolumab/ipilimumab has demonstrated benefit in other patient populations with RCC.In April 2018, the FDA approved the combination of nivolumab and ipilimumab as a frontline treatment for intermediate- and poor-risk patients with advanced RCC.² Additionally, in January 2021, the combination of cabozantinib (Cabometyx) and nivolumab earned FDA approval for the frontline treatment of patients with advanced RCC.³ Furthermore, cabozantinib plus nivolumab/ipilimumab generated a significant improvement in progression-free survival (PFS) vs nivolumab/ipilimumab in patients with previously untreated advanced intermediate- or poor-risk RCC, meeting the primary end point of the phase 3 COSMIC-313 trial (NCT03937219).⁴

The randomized, double-blind, placebo-controlled CheckMate-914 trial evaluated the combination of nivolumab and ipilimumab vs placebo in part A, and nivolumab monotherapy vs nivolumab plus ipilimumab vs placebo in part B. Patients were required to be at least 18 years of age with localized RCC at a moderate or high risk of relapse who had their kidney tumor resected with negative surgical margins obtained.⁵ Randomization needed to occur between 4 and 12 weeks following nephrectomy.

Additional inclusion criteria included tumors with a predominantly clear cell histology, including patients with sarcomatoid features; no clinical or radiological evidence of macroscopic residual disease or distant metastases after nephrectomy; and an ECOG performance status of 0 or 1.

Exclusion criteria included active known or suspected autoimmune disease; a known history of a positive test for HIV or known AIDS; prior treatment with an anti–PD-1, anti–PD-L1, anti–PD-L2, or anti–CTLA-4 antibody, or any other agent targeting T-cell co-stimulation or checkpoint pathways; or any severe or serious acute or chronic medical or psychiatric condition.

DFS served as the primary end point in parts A and B. Secondary end points in both parts of the trial included overall survival and the incidence of adverse effects. DFS for nivolumab monotherapy vs the nivolumab/ipilimumab combination will also be accessed as a secondary end point in part B, which is ongoing.

Findings from part A of CheckMate-914 showed that the safety profile of nivolumab plus ipilimumab was consistent with previously reported studies of the combination in patients with solid tumors.

References

1. Bristol Myers Squibb provides update on CheckMate-914 trial evaluating Opdivo (nivolumab) plus Yervoy (ipilimumab) as adjuvant treatment of localized renal cell carcinoma. News release. Bristol Myers Squibb. July 29, 2022. Accessed August 1, 2022. https://bit.ly/3Q8sLYF
2. FDA approves nivolumab plus ipilimumab combination for intermediate or poor-risk advanced renal cell carcinoma. News release. FDA. April 16, 2018. Accessed August 1, 2022. https://bit.ly/3c1TnMj
3. FDA approves nivolumab plus cabozantinib for advanced renal cell carcinoma. News release. FDA. January 22, 2021. August 1, 2022. http://bit.ly/2Mjrt1i
4. Exelixis announces cabozantinib in combination with nivolumab and ipilimumab significantly improved progression-free survival in phase 3 COSMIC-313 pivotal trial in patients with previously untreated advanced kidney cancer. News release. Exelixis. July 11, 2022. Accessed August 1, 2022. https://bwnews.pr/3NSar4E
5. A study comparing nivolumab, nivolumab in combination with ipilimumab and placebo in participants with localized kidney cancer who underwent surgery to remove part of a kidney (CheckMate 914). ClinicalTrials.gov. Updated July 20, 2022. Accessed August 1, 2022. https://clinicaltrials.gov/ct2/show/NCT03138512