Bempegaldesleukin Plus Nivolumab Not Effective in Treatment-Naïve Unresectable, Metastatic Melanoma

All primary end points in the phase 3 study of bempegaldesleukin plus nivolumab for the treatment of metastatic melanoma were missed, but analyses are ongoing.


Bempegaldesleukin (NKTR-214) in combination with nivolumab (Opdivo) administered as treatment for patients with previously untreated, unresectable or metastatic melanoma did not improve progression-free survival (PFS) or show a beneficial objective response rate (ORR) compared with nivolumab alone, missing the coprimary end points of the phase 3 PIVOT IO-001 study.1

Results from an efficacy and safety review by an Independent Data Monitoring Committee further showed no statistical significance in the third primary end point of overall survival (OS), leading the collaborating companies Bristol Myers Squibb and Nektar to unblind the study and discontinue enrollment, according to the release.

“As a leader in developing innovative therapies for patients with cancer, we have continued to explore novel strategies that may expand treatment benefits to more patients with advanced disease,” said Jonathan Cheng, senior vice president and head of oncology development, Bristol Myers Squibb, in the press release. “We are disappointed with the results of this trial, which we had hoped would lead to a new therapeutic option to treat metastatic melanoma.”

Originally in the PIVOT IO-001 study (NCT03635983), 781 patients were enrolled to assess the efficacy and safety of the combination based on ORR and PFS by Blinded Independent Central Review and based on OS. Secondary efficacy end points explored in the study include clinical benefit rate, duration of response, time to response, ORR in the investigational and biomarker populations, PFS in the investigational and biomarker populations, and OS in the biomarker population.2

Secondary safety end points of the study include the incidence of adverse events (AEs), incidence of serious AEs, and the incidence of laboratory abnormalities.

All patients enrolled had histologically confirmed stage III (unresectable) or stage IV melanoma and were previously untreated. Further, all patients were required to have an ECOG performance status of ≤1 if 18 years of age or older, or a Lansky Performance Score ≥ 80%, between the ages of 12 and 17 years.

With patients in the study now unblinded, OS analyses will continue in the study. The companies also plan to review the data and share the results with the scientific community. Four other studies of bempegaldesleukin in combination with nivolumab continue to investigate the efficacy and safety of the combination in renal cell carcinoma and bladder cancer.1

“While we are surprised and deeply disappointed in these results for the melanoma study, we will continue to await initial results from our first 2 ongoing studies in renal cell carcinoma and urothelial cancer, which are currently expected in the first half of 2022,” said Jonathan Zalevsky, chief research and development officer of Nektar Therapeutics, in the press release.


1. Bristol Myers Squibb and Nektar announce update on phase 3 PIVOT IO-001 trial evaluating bempegaldesleukin (BEMPEG) in combination with Opdivo (nivolumab) in previously untreated unresectable or metastatic melanoma. News release. Bristol Myers Squibb and Nektar. March 14, 2022. Accessed March 14, 2022.

2. A study of NKTR-214 combined with nivolumab vs nivolumab alone in participants with previously untreated inoperable or metastatic melanoma. Updated January 20, 2022. Accessed March 14, 2022.

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