Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma

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


J Clin Oncol. 2021;39(26):2914-2925. 

In This Article

Abstract and Introduction


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 −78.5% (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 CD8+ and CD4+ T cells were seen in blood after treatment, driven by cytokines with effector functions. Early on-treatment blood biomarkers (CD8+ 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.