BMS’s Opdivo fails for second time in late-stage kidney cancer trial

Published: Jan 29, 2024

By Tristan Manalac

BioSpace

Bristol Myers Squibb’s PD-1 blocker Opdivo (nivolumab) failed part B of the Phase III CheckMate-914 study, bearing no significant disease-free survival benefit for patients with localized renal cell carcinoma who are at high-risk of relapse after surgery.

After a median follow-up of 27 months, Opdivo failed to elicit a significant improvement in disease-free survival (DFS), as assessed by blinded independent central review (BICR), versus placebo. Opdivo’s effects yielded a hazard ratio estimate of 0.87, with a p-value of 0.3952, according to the abstract presented on Saturday at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU 2024).

The probabilities of DFS at 12 months were 83.3% in the Opdivo arm versus 78.2% in the placebo group. At 18 months, these estimates changed only slightly to 78.4% and 75.4%, respectively. Both treatment arms also did not reach median DFS at the time of analysis.

Because Opdivo missed its primary efficacy endpoint, CheckMate-914 will no longer continue on to a formal overall survival analysis, study lead author Robert Motzer said during the oral presentation at ASCO GU 2024, as reported by Targeted Oncology.

CheckMate-914 is a randomized, double-blinded and two-part trial. In part A, the study combined Opdivo with BMS’s own anti-CTLA4 therapy Yervoy (ipilimumab) and assessed it as an adjuvant treatment for renal cell carcinoma (RCC) patients who had undergone nephrectomy but were still at a high risk of disease relapse.

In July 2022, BMS announced that its combo regimen had failed part A of CheckMate-914, likewise eliciting no significant improvement in BICR-assessed DFS in treated patients.

Part B assessed Opdivo as a monotherapy versus placebo in the same setting and in the same patient population.

In addition to assessing efficacy, BMS’s ASCO GU 2024 presentation also unveiled safety data for the Opdivo monotherapy, showing that the PD-1 blocker was associated with a higher rate of any-grade treatment-related adverse events than placebo—72.5% versus 51.7%. Grade 3 to 4 treatment-related adverse events were likewise more common in the Opdivo group.

Overall, 9.6% of Opdivo-treated patients dropped out of the study, as opposed to only 1% in the placebo group.

BMS’s disappointing readout at ASCO GU 2024 comes as one of its chief competitors—Merck’s blockbuster PD-1 inhibitor Keytruda (pembrolizumab)—demonstrated strong clinical benefit in the same indication.

In KEYNOTE-564, compared with placebo, Keytruda reduced the risk of death by 38% in RCC patients who are at intermediate-high or high risk of recurrence after nephrectomy. The results come after an earlier readout in June 2021, which showed that the PD-1 inhibitor cut the risk of recurrence or death by 32% in these patients.

Source: BioSpace