Diab et al. reported the safety and clinical efficacy of CD122-preferential interleukin-2 pathway agonist bempegaldesleukin (BEMPEG) plus nivolumab in a first-line advanced disease melanoma setting. The BEMPEG plus nivolumab combination was well tolerated, and efficacy compared favorably to nivolumab alone in 38 evaluable patients. The median PFS was 30.9%, the OS at 24 month was 77%, and 47.4% of patients experienced complete clearance of target lesions. Treatment induced polyfunctional CD8+ and CD4+ T cell responses and baseline polyfunctionality. HLA-E expression and an increase in eosinophils in blood were associated with higher ORR.
Contributed by Shishir Pant
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 2 years; 38 were efficacy-evaluable (³ 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.
Author Info: (1) The University of Texas MD Anderson Cancer Center, Houston, TX. (2) University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA. (3) University of Californ
Author Info: (1) The University of Texas MD Anderson Cancer Center, Houston, TX. (2) University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA. (3) University of California, La Jolla, San Diego, CA. (4) Azienda Ospedaliera Universitaria Senese, Siena, Italy. (5) Providence Cancer Institute and Earle A. Chiles Research Institute, Portland, OR. (6) University of Colorado Cancer Center, Aurora, CO. (7) Inova Schar Cancer Institute, Fairfax, VA. (8) Polish Mother's Memorial Hospital-Research Institute, Lodz, Poland. (9) Roswell Park Comprehensive Cancer Center, Buffalo, NY. (10) Virginia Cancer Specialists, Fairfax, VA. (11) Perlmutter Cancer Center at NYU Langone Medical Center, New York, NY. (12) Nektar Therapeutics, San Francisco, CA. (13) Nektar Therapeutics, San Francisco, CA. (14) Nektar Therapeutics, San Francisco, CA. (15) Nektar Therapeutics, San Francisco, CA. (16) Nektar Therapeutics, San Francisco, CA. (17) Nektar Therapeutics, San Francisco, CA. (18) Nektar Therapeutics, San Francisco, CA. (19) Nektar Therapeutics, San Francisco, CA. (20) Yale School of Medicine, New Haven, CT. (21) Yale School of Medicine, New Haven, CT.
