Global Clinical Development of Bempegaldesleukin Plus Nivolumab for RCC and Bladder Cancer Discontinued

Findings from a preplanned analysis assessing 2 clinical trials of bempegaldesleukin plus nivolumab in renal cell carcinoma and bladder cancer led to a decision to end the combination’s global clinical development program and discontinue all other ongoing clinical trials.

The global clinical development and ongoing trials of bempegaldesleukin (NKTR-214) and nivolumab (Opdivo) for patients with previously untreated advanced or metastatic renal cell carcinoma (RCC) and cisplatin-ineligible, locally advanced or metastatic urothelial cancer were halted, according to a press release from Nektar Therapeutics and Bristol Myers Squibb.

The decision followed findings from pre-planned analyses of 2 clinical trials assessing bempegaldesleukin and nivolumab in patients with RCC and bladder cancer.

“As a leader in developing innovative therapies for patients with cancer, we are committed to continuing to explore novel combinations and pathways and advancing research that may help [patients with] cancer achieve better outcomes. We are immensely grateful to the patients and investigators who participated in these studies,” Jonathan Cheng, senior vice president and head of oncology development at Bristol Myers Squibb, said in a press release.

In the phase 3 PIVOT-09 study (NCT03729245), the combination was assessed vs investigator’s choice of tyrosine kinase inhibitor, including sunitinib (Sutent) or cabozantinib (Cabometyx), in a population of patients with previously treated advanced or metastatic RCC. A final objective response rate (ORR) analysis by blinded independent central review highlighted that bempegaldesleukin and nivolumab did not meet the prespecified boundary for significance vs the control group. Additionally, the interim overall survival (OS) analysis did not meet the prespecified boundary for statistical significance in both groups. The trial was unblinded due to the lack of clinical benefit in the combination arm vs the control arm, and no additional OS analyses will be performed.

A total of 623 patients were enrolled on the trial and randomized 1:1. Those in the experimental arm received a 0.006 mg/kg dose of bempegaldesleukin and a 360 mg dose of nivolumab every 3 weeks, which was delivered intravenously in an outpatient setting. Treatment continued until disease recurrence, unacceptable toxicity, or withdrawal of consent to upwards of 24 months.

Moreover, bempegaldesleukin plus nivolumab was assessed as part of the phase 2 PIVOT-10 study (NCT03785925) in patients with cisplatin-ineligible advanced or metastatic urothelial cancer. In this trial, the combination did not reach an efficacy threshold to warrant continuing development in this patient population, according to a final ORR analysis by blinded independent central review.

The single-arm study enrolled 192 patients who underwent treatment with the experimental combination until experiencing disease recurrence, unacceptable toxicity, or consent withdrawal for up to 24 months.

Nektar Therapeutics and Bristol Myers Squibb are set to review and present findings from both trials.

Notably, the combination was also assessed in the phase 3 PIVOT IO-001 study (NCT03635983) in a population of patients with previously treated inoperable or metastatic melanoma. However, findings from the trial led investigators to discontinue 2 pivotal studies in the melanoma space in March 2022.


Nektar and Bristol Myers Squibb announce update on clinical development program for bempegaldesleukin (BEMPEG) in combination with Opdivo (nivolumab). News release. Nektar Therapeutics and Bristol Myers Squibb. April 14, 2022. Accessed April 18, 2022.

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