Bempegaldesleukin Plus Nivolumab Misses Efficacy End Points in Metastatic Melanoma


Manufacturers will unblind trials evaluating bempegaldesleukin/nivolumab in melanoma in light of the final progression-free survival and overall response rates analyses.

Bempegaldesleukin Plus Nivolumab Misses Efficacy End Points in Metastatic Melanoma

Bempegaldesleukin Plus Nivolumab Misses Efficacy End Points in Metastatic Melanoma

Treatment with bempegaldesleukin (NKTR-214) in combination with nivolumab (Opdivo) did not result in superior clinical benefit as a first-line treatment for patients with previously untreated unresectable or metastatic melanoma, according to a news release.

Following an Independent Data Monitoring Committee review of the efficacy and safety results from the phase 3 PIVOT IO-001 study (NCT03635983), the manufacturers were informed that the trial did not meet the primary endpoints for PFS and ORR. Moreover, the committee also informed the companies that at the first interim analysis, the trial had not reached statistical significance for the third primary endpoint: overall survival (OS).

Because of these results, the manufacturers have chosen to unblind the trial and forego additional analyses for OS. In addition, as a result of the PIVOT IO-001 study, the ongoing PIVOT-12 study (NCT04410445), which is assessing the combination in an adjuvant setting, will halt enrollment as well as unblind current participants. Patients on both trials will receive counselling for their treatment options and will be able to continue therapy upon physician approval.

“While we are surprised and deeply disappointed in these results for the melanoma study, we will continue to await initial results from our first two 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, the developer of bempegaldesleukin. “We look forward to collaborating with [Bristol Myers Squibb] to evaluate the data from these other studies to guide the future development of bempegaldesleukin.”

Previously reported data from the phase 1/2 PIVOT-02 trial (NCT02983045) had showcased that the combination elicited promising antitumor activity in patients with metastatic melanoma.

The study enrolled patients with histologically confirmed stage III (unresectable) or stage IV (metastatic) melanoma, a known BRAF mutation (V600E or V600K), PD-L1 immunohistochemistry status, adequate organ function, and who were 18 years and older. Patients with prior treatment for melanoma in either the neoadjuvant, adjuvant, locally advanced, or metastatic settings were excluded, as were patients with previous IL-2 therapy, uveal melanoma, or active brain metastases.

These patients received with 0.006 mg/kg intravenous bempegaldesleukin along with 360-mg of nivolumab once every 3 weeks. This continued until 1 of the following occurred: disease progression, death, unacceptable toxicity, symptomatic deterioration, achievement of maximal response, or either the patient or provider decided to withdraw. Responsive patients continued treatment for 2 years.

Among the response-evaluable population, the median change in target lesion size was a 78.5% reduction. Notably, 47.4% of patients reported that their target lesion completely cleared.

After a median follow-up of 29 months, the objective response rate was 52.6% and the complete response rate was 34.2%. Median overall survival (OS) was not reached, although, at 24 months, the OS rate was 77.0% (95% CI, 60.4%-87%).

The PIVOT IO-001 study was launched to confirm the data observed in this trial.

“We are disappointed with the results of this trial, which we had hoped would lead to a new therapeutic option to treat metastatic melanoma,” Jonathan Cheng, senior vice president and head of oncology development, Bristol Myers Squibb, stated in the press release. “We express our gratitude to the patients, caregivers and investigators who chose to participate in these trials.”


  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 Therapeutics; March 14, 2022. Accessed March 15, 2022.
  2. Diab A, Tykodi SS, Daniels GA, et al. Bempegaldesleukin plus nivolumab in first-line metastatic melanoma. J Clin Oncol. 2021;39(26):2914-2925. doi:10.1200/JCO.21.00675.
  3. Novel immunotherapy combination produces durable response in frontline metastatic melanoma. The University of Texas MD Anderson Cancer Center. News release. July 13, 2021. Accessed March 15, 2022.

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