Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma

Adi Diab, Scott S. Tykodi, Gregory A. Daniels, Michele Maio, Brendan D. Curti, Karl D. Lewis, Sekwon Jang, Ewa Kalinka, Igor Puzanov, Alexander I. Spira, Daniel C. Cho, Shanhong Guan, Erika Puente, Tuan Nguyen, Ute Hoch, Sue L. Currie, Wei Lin, Mary A. Tagliaferri, Jonathan Zalevsky, Mario SznolMichael E. Hurwitz

Research output: Contribution to journalArticlepeer-review


PURPOSE Therapies that produce deep and durable responses in patients with metastatic melanoma are needed. This phase II cohort from the international, single-arm PIVOT-02 study evaluated the CD122-preferential interleukin-2 pathway agonist bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) in first-line metastatic melanoma. METHODS A total of 41 previously untreated patients with stage III/IV melanoma received BEMPEG 0.006 mg/kg plus NIVO 360 mg once every 3 weeks for # 2 years; 38 were efficacy-evaluable ($ 1 postbaseline scan). Primary end points were safety and objective response rate (blinded independent central review); other end points included progression-free survival, overall survival (OS), and exploratory biomarkers. RESULTS At 29.0 months’ median follow-up, the objective response rate was 52.6% (20 of 38 patients), and the complete response rate was 34.2% (13 of 38 patients). Median change in size of target lesions from baseline was 278.5% (response-evaluable population); 47.4% (18 of 38 patients) experienced complete clearance of target lesions. Median progression-free survival was 30.9 months (95% CI, 5.3 to not estimable). Median OS was not reached; the 24-month OS rate was 77.0% (95% CI, 60.4 to 87.3). Grade 3 and 4 treatment-related and immune-mediated adverse events occurred in 17.1% (7 of 41) and 4.9% (2 of 41) of patients, respectively. Increased polyfunctional responses in CD81 and CD41 T cells were seen in blood after treatment, driven by cytokines with effector functions. Early on-treatment blood biomarkers (CD81 polyfunctional strength difference and eosinophils) correlated with treatment response. CONCLUSION BEMPEG in combination with NIVO was tolerated, with relatively low rates of grade 3 and 4 treatment-related and immune-mediated adverse events. The combination had encouraging antitumor activity in first-line metastatic melanoma, including an extended median progression-free survival. Exploratory analyses associated noninvasive, on-treatment biomarkers with response, before radiologic evidence was observed.

Original languageEnglish (US)
Pages (from-to)2914-2925
Number of pages12
JournalJournal of Clinical Oncology
Issue number26
StatePublished - Sep 10 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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