Bempegaldesleukin plus nivolumab in first-line metastatic melanoma tolerated with encouraging antitumour activity
March 8, 2022
Abstract
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.
Source:
Diab, A., Tykodi, S. S., Daniels, G. A., Maio, M., Curti, B. D., Lewis, K. D., Jang, S., Kalinka, E., Puzanov, I., Spira, A. I., Cho, D. C., Guan, S., Puente, E., Nguyen, T., Hoch, U., Currie, S. L., Lin, W., Tagliaferri, M. A., Zalevsky, J., … Hurwitz, M. E. (2021). Bempegaldesleukin plus nivolumab in first-line metastatic melanoma. Journal of Clinical Oncology, 39(26), 2914–2925. https://doi.org/10.1200/jco.21...