Bempegaldesleukin Plus Nivolumab Appears Safe and Effective in First-Line Metastatic Melanoma


Bempegaldesleukin plus nivolumab demonstrated positive antitumor activity while maintaining a tolerable safety profile in the PIVOT-02 trial for patients with previously untreated metastatic melanoma in the first-line setting.

The combination of bempegaldesleukin (BEMPEG) plus nivolumab demonstrated encouraging antitumor activity with low rates of grade 3 and 4 treatment-related and immune-mediated adverse effects (AEs) in the first-line treatment of patients with metastatic melanoma, according to data from the phase 2 PIVOT-02 study (NCT02983045).1

After a median follow-up of 29.0 months for the primary analysis (IQR, 15.7-32.3 months), investigators reported an overall response rate (ORR) of 52.6% (95% CI, 35.8%-69.0%), as evaluated by blinded independent central review (BICR). Complete responses (CRs) were observed in 13 patients (34.2%), with a median time to onset of first response of 2.0 months (range, 1.5-4.1 months) and 7.9 months (range, 1.5-15.2 months) to CR. ORR via investigator review was consistent with the ORR via BICR (52.6% for each, respectively). CRs were observed via local investigator assessment in 7 patients.

“These data provide preliminary evidence to support the safety and efficacy of BEMPEG plus nivolumab in patients with previously untreated metastatic melanoma,” the study authors wrote. “The responses appeared deep and durable, with 90% (18 of 20) of responding patients achieving 100% reduction in their target lesions [vs] baseline, and rates of grade 3 (or higher) events were within acceptable limits.”

The study enrolled 41 patients with unresectable or metastatic melanoma across 12 sites in 3 countries from March 27, 2017, to March 28, 2018. All patients included received 1 or more doses of BEMPEG plus nivolumab and were evaluable for safety. Thirty-eight patients were evaluable for efficacy after undergoing 1 or more postbaseline scans.

Patients in the experimental arm received BEMPEG at a dose of 0.006 mg/kg intravenously plus nivolumab 360 mg once every 3 weeks up to a certain point, including disease progression, death, or unacceptable toxicity, among other things.

At the point of data cutoff, no patients from the population remained on the treatment with the experimental combination. Reasons for discontinuation included progressive disease by RECIST (n = 14), AEs (n = 9), patient decision (n = 9), achievement of maximal response (n = 8), and clinical progression (n = 1).

“There is an unmet need for novel, first-line combinations to extend the treatment benefit of immunotherapy to more patients with metastatic melanoma, without substantially adding toxicity,” the investigators wrote. “This phase 2 cohort from the international, single-arm PIVOT-02 study evaluated the novel IL-2 pathway agonist and ICI immunotherapy combination of BEMPEG plus NIVO in patients with previously untreated, unresectable, or metastatic melanoma.”

Additional data from the study indicated that at data cut-off patients experienced a median PFS of 30.9 months (95% CI, 5.3–not estimable). The median overall survival (OS) was not reached, and the OS at 24-months was 82.3% (95% CI, 66.4%-91.1%) and 77.0% (95% CI, 60.4%-87.3%) in the experimental and control groups, respectively.

“Our study shows that the combination of BEMPEG and nivolumab is safe and effective,” lead and corresponding author Adi Diab, MD, associate professor of Melanoma Medical Oncology, said in a press release.2 “We are encouraged by the potential of a new treatment option for newly diagnosed patients with advanced melanoma, and we look forward to the results from the Phase 3 study, which is enrolling now.”

Treatment-related AEs were observed in 95.1% of patients, with the most common any-grade AEs including flu-like symptoms, rash, fatigue, pruritus, arthralgia, and nausea. Grade 3 or 4 treatment-related AEs were seen in 7 patients. Moreover, 5 patients discontinued treatment due to treatment-related AEs, including blood creatinine increased, cerebrovascular accident, malaise, peripheral edema, and pharyngitis.

The study’s main limitations included the small sample size of 41 total patients and the single-arm design. Similarly, phase 1/2 trials have the potential for selection bias, potentially skewing the generalizability of the data.


  1. Diab A, Tykodi SS, Daniels GA, et al. Bempegaldesleukin plus nivolumab in first-line metastatic melanoma. J Clin Oncol. Published online ahead of print, July 13, 2021. doi:10.1200/JCO.21.00675
  2. Novel immunotherapy combination produces durable response in frontline metastatic melanoma. News release. MD Anderson Cancer Center. Published July 13, 2021. Accessed July 15, 2021.
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