Previously Untreated Advanced Melanoma: Addition of Bempegaldesleukin to Nivolumab

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In the phase III PIVOT IO 001 trial reported in the Journal of Clinical Oncology, Adi Diab, MD, and colleagues found that the addition of bempegaldesleukin, a pegylated interleukin-2 cytokine prodrug, to nivolumab did not improve treatment outcomes in previously untreated patients with advanced melanoma.

Adi Diab, MD

Adi Diab, MD

Study Details

In the open-label trial, 783 patients with stage III unresectable or stage IV melanoma from sites in 26 countries were randomly assigned between October 2018 and December 2021. They received either bempegaldesleukin at 0.006 mg/kg followed by nivolumab at 360 mg every 3 weeks (n = 391) or nivolumab alone at 360 mg every 3 weeks (n = 392). The primary endpoints of the trial were objective response rate (in the population of patients with ≥ 6 months follow-up) and progression-free survival on blinded independent central review and overall survival.

Response and Survival Outcomes

Objective response was observed in 75 (27.7%, 95% confidence interval [CI] = 22.4%–33.4%) of 271 patients in the bempegaldesleukin/nivolumab group vs 98 (36.0%, 95% CI = 30.3%–42.0%) of 272 in the nivolumab group (odds ratio = 0.66, 99.9% CI = 0.35–1.24, P = .0311). Complete response was observed in 8.1% vs 12.5% of patients. Median duration of response was 29.67 months (95% CI = 18.89 months to not reached) vs not reached (95% CI = 26.74 months to not reached).

Median progression-free survival was 4.17 months (95% CI = 3.52–5.55 months) in the bempegaldesleukin/nivolumab group vs 4.99 months (95% CI = 4.14–7.82 months) in the control group (hazard ratio [HR] = 1.09, 97% CI = 0.88–1.35, P = .3988); 12-month rates were 31.8% vs 39.9%.

Median overall survival was 29.67 months (95% CI = 22.14 months to not reached) in the combination group vs 28.88 months (95% CI = 21.32 months to not reached) in the control group (HR = 0.94, 99.929% CI = 0.59–1.48, P = .6361); the 24-month rate in both groups was 55.5%.  


  • The addition of bempegaldesleukin to nivolumab did not improve objective response rate, progression-free survival, or overall survival.
  • For the combination group vs control group, objective response rates were 27.7% vs 36.0%, and median progression-free and overall survival were 4.17 vs 4.99 months and 29.7 vs 28.9 months, respectively.

Adverse Events

Grade 3 or 4 treatment-related adverse events occurred in 21.7% of the combination group vs 11.5% of the control group. Treatment-related serious adverse events occurred in 10.1% vs 5.5% of patients. Treatment-related adverse events led to discontinuation of any component of study treatment in 10.1% vs 6.8%. In the combination group, the most common categories for cytokine-associated adverse events of any grade included flu-like symptoms (66.4%), rash/pruritus (55.8%), and asthenic conditions (43.2%). Ischemic cerebrovascular events occurred in 10 patients (2.6%; grade 3­–4 in 5 [1.3%]) in the combination group vs 3 patients (0.8%; grade 3–4 in 2 [0.5%]) in the control group. Treatment-related death occurred in three patients vs one patient.

The investigators concluded, “The PIVOT IO 001 study did not meet its primary endpoints of objective response rate, progression-free survival, or overall survival. Increased toxicity was observed with bempegaldesleukin plus nivolumab vs nivolumab.”

Dr. Diab, of the Melanoma Medical Oncology Department, The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Bristol Myers Squibb. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.