Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
oregon; portland; chiles
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.
Earle A. Chiles Research Institute
Diab, Adi; Tykodi, Scott S; Daniels, Gregory A; Maio, Michele; Curti, Brendan D; Lewis, Karl D; Jang, Sekwon; Kalinka, Ewa; Puzanov, Igor; Spira, Alexander I; Cho, Daniel C; Guan, Shanhong; Puente, Erika; Nguyen, Tuan; Hoch, Ute; Currie, Sue L; Lin, Wei; Tagliaferri, Mary A; Zalevsky, Jonathan; Sznol, Mario; and Hurwitz, Michael E, "Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma." (2021). Articles, Abstracts, and Reports. 5075.