TY - JOUR
T1 - Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma
AU - Diab, Adi
AU - Tykodi, Scott S.
AU - Daniels, Gregory A.
AU - Maio, Michele
AU - Curti, Brendan D.
AU - Lewis, Karl D.
AU - Jang, Sekwon
AU - Kalinka, Ewa
AU - Puzanov, Igor
AU - Spira, Alexander I.
AU - Cho, Daniel C.
AU - Guan, Shanhong
AU - Puente, Erika
AU - Nguyen, Tuan
AU - Hoch, Ute
AU - Currie, Sue L.
AU - Lin, Wei
AU - Tagliaferri, Mary A.
AU - Zalevsky, Jonathan
AU - Sznol, Mario
AU - Hurwitz, Michael E.
N1 - Publisher Copyright:
Copyright © 2022 American Society of Clinical Oncology. All rights reserved.
PY - 2021/9/10
Y1 - 2021/9/10
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.21.00675
DO - 10.1200/JCO.21.00675
M3 - Article
C2 - 34255535
AN - SCOPUS:85116171586
SN - 0732-183X
VL - 39
SP - 2914
EP - 2925
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 26
ER -