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Chawla SP , Van Tine BA , Pollack SM , Ganjoo KN , Elias AD , Riedel RF , Attia S , Choy E , Okuno SH , Agulnik M , von Mehren M , Livingston MB , Keedy VL , Verschraegen CF , Philip T , Bohac GC , Yurasov S , Yakovich A , Lu H , Chen M , Maki RG
Phase II Randomized Study of CMB305 and Atezolizumab Compared With Atezolizumab Alone in Soft-Tissue Sarcomas Expressing NY-ESO-1
J Clin Oncol. 2021 Jul 14 :Jco2003452
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PURPOSE: CMB305 is a heterologous prime-boost vaccination regimen created to prime NY-ESO-1-specific CD8 T-cell populations and then activate the immune response with a potent TLR-4 agonist. This open-label randomized phase II trial was designed to investigate the efficacy and safety of adding the CMB305 regimen to atezolizumab (anti-programmed death ligand-1 therapy) in comparison with atezolizumab alone in patients with synovial sarcoma or myxoid liposarcoma. PATIENTS AND METHODS: Patients with locally advanced, relapsed, or metastatic synovial sarcoma or myxoid liposarcoma (any grade) were randomly assigned to receive CMB305 with atezolizumab (experimental arm) or atezolizumab alone (control arm). The primary end points were progression-free survival (PFS) and overall survival (OS) analyzed using the Kaplan-Meier method. Safety and immune responses were assessed. RESULTS: A total of 89 patients were enrolled; 55.1% had received ≥ 2 prior lines of chemotherapy. Median PFS was 2.6 months and 1.6 months in the combination and control arms, respectively (hazard ratio, 0.9; 95% CI, 0.6 to 1.3). Median OS was 18 months in both treatment arms. Patients treated with combination therapy had a significantly higher rate of treatment-induced NY-ESO-1-specific T cells (P = .01) and NY-ESO-1-specific antibody responses (P < .0001). In a post hoc analysis of all dosed patients, OS was longer (36 months) in the subset who developed anti-NY-ESO-1 T-cell immune response (hazard ratio, 0.3; P = .02). CONCLUSION: Although the combination of CMB305 and atezolizumab did not result in significant increases in PFS or OS compared with atezolizumab alone, some patients demonstrated evidence of an anti-NY-ESO-1 immune response and appeared to fare better by imaging than those without such an immune response. Combining prime-boost vaccines such as CMB305 with anti-programmed death ligand-1 therapies merits further evaluation in other clinical contexts.
1527-7755 Chawla, Sant P Van Tine, Brian A Orcid: 0000-0003-4572-6668 Pollack, Seth M Ganjoo, Kristen N Elias, Anthony D Orcid: 0000-0002-6509-9211 Riedel, Richard F Orcid: 0000-0001-5412-8710 Attia, Steven Choy, Edwin Orcid: 0000-0001-9896-8084 Okuno, Scott H Agulnik, Mark Orcid: 0000-0003-3513-3519 von Mehren, Margaret Orcid: 0000-0001-6158-890x Livingston, Michael B Keedy, Vicki L Orcid: 0000-0002-7213-7562 Verschraegen, Claire F Orcid: 0000-0001-6544-3089 Philip, Tony Orcid: 0000-0001-6014-1292 Bohac, G Chet Yurasov, Sergey Orcid: 0000-0003-1783-7731 Yakovich, Adam Lu, Hailing Orcid: 0000-0002-6418-9688 Chen, Michael Maki, Robert G Orcid: 0000-0002-9853-2528 Journal Article United States J Clin Oncol. 2021 Jul 14:JCO2003452. doi: 10.1200/JCO.20.03452.