A phase II randomized study of CMB305 and atezolizumab versus atezolizumab in NY-ESO-1+ soft tissue sarcoma: Analysis of immunogenicity, tumor control, and patient survival.

person Sant P. Chawla Sarcoma Oncology Research Center, Santa Monica, CA info_outline Sant P. Chawla, Brian Andrew Van Tine, Seth Pollack, Kristen N. Ganjoo, Anthony D. Elias, Richard F. Riedel, Steven Attia, Edwin Choy, Scott H. Okuno, Mark Agulnik, Margaret von Mehren, Michael B. Livingston, Vicki Leigh Keedy, Claire F. Verschraegen, Tony Philip, Gerry C. Bohac, Sergey Yurasov, Hailing Lu, Michael Chen, Robert G. Maki, Stephen Gottschalk

Authors person Sant P. Chawla Sarcoma Oncology Research Center, Santa Monica, CA info_outline Sant P. Chawla, Brian Andrew Van Tine, Seth Pollack, Kristen N. Ganjoo, Anthony D. Elias, Richard F. Riedel, Steven Attia, Edwin Choy, Scott H. Okuno, Mark Agulnik, Margaret von Mehren, Michael B. Livingston, Vicki Leigh Keedy, Claire F. Verschraegen, Tony Philip, Gerry C. Bohac, Sergey Yurasov, Hailing Lu, Michael Chen, Robert G. Maki, Stephen Gottschalk Organizations Sarcoma Oncology Research Center, Santa Monica, CA, Washington University in St. Louis, St. Louis, MO, Fred Hutchinson Cancer Research Center, Seattle, WA, Stanford Cancer Institute, Stanford, CA, University of Colorado Comprehensive Cancer Center, Aurora, CO, Duke University Medical Center, Durham, NC, Mayo Clinic, Jacksonville, FL, Massachusetts General Hospital, Boston, MA, Mayo Clinic, Rochester, MN, Northwestern University Feinberg School of Medicine, Chicago, IL, Fox Chase Cancer Center, Philadelphia, PA, Levine Cancer Institute, Atrium Health, Charlotte, NC, Vanderbilt University Medical Center, Nashville, TN, University of Vermont Cancer Center, Burlington, VT, Hofstra North Shore-LIJ School of Medcn, New Hyde Park, NY, Immune Design, San Francisco, CA, ImClone Systs, New York, NY, Immune Design, Seattle, WA, Immune Design Corp., South San Francisco, CA, Northwell Cancer Institute and Cold Spring Harbor Laboratory, New Hyde Park, NY, St. Jude Children's Research Hospital Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: CMB305 (C) is an immunotherapy designed to generate an anti-NY-ESO-1 immune response (IR). C consists of a dendritic cell-targeting lentiviral vector encoding NY-ESO-1 gene (LV305), and a TLR-4 agonist NY-ESO-1 recombinant protein plus GLA-SE (G305). A Phase 1 study demonstrated C is safe, generates IR and conveys a median overall survival (mOS) of 23.7 months (15.5, not reached [NR]) for soft tissue sarcomas & 29.2 months (12.2, NR) for synovial sarcoma (SS) (ESMO 2018). We evaluated efficacy and safety of C and atezolizumab (A) vs A alone in NY-ESO-1 + SS and myxoid round cell liposarcoma (MRCL). Methods: A prospective randomized open label phase 2 study of C (LV305 Intradermal Days 0, 14, 42, 70 + G305 Intramuscular Days 28, 56, 84 then q 6wk up to one year (yr)) + A (1200mg IV q3wk) vs A alone in advanced NY-ESO-1+ SS/MRCL. Primary endpoints of OS and progression-free survival (PFS); secondary endpoints of safety, IR, and response rate and post hoc analysis by line of therapy. Results: 88 patients (pts) were enrolled and dosed. Arm C+A: median age 48 yrs, 73% SS, 98% relapsed metastatic, 73% ≥2 prior lines chemotherapy; Arm A: 47 yrs, 67% SS, 84% relapsed metastatic, 53% ≥2 prior lines chemotherapy. Most treatment-related adverse events (TRAE) Grade 1/2, no treatment related deaths. Summary of clinical outcomes. Conclusions: Despite no major differences in PFS and OS between the treatment arms (Arm C+A had more advanced disease and more prior lines of chemotherapy), Arm A +C achieved PRs, a higher level of anti-NY-ESO-1 IR, and pts with IR had numerically superior outcomes. Moreover, the clinical benefit of C+A in earlier lines of therapy warrant further study. Clinical trial information: NCT02609984 Clinical Outcomes (median) Months (or %) (95% confidence interval). Clinical Outcome Arm C+A Arm A OS 18.2 (10.1, 22.1) 18.0 (15.3, 26.5) PFS 2.8 (1.4, 3.0) 1.6 (1.5, 2.8) ORR 4.4% (0.5%, 15.1%) 0 % (0.0%, 8.0%) Grade 3 TRAE 6.7% 7.0% Arm C+A pts with only 1 prior line & SD or better, mOS 24.9 mo (11.0, NR) vs Arm A 17.7 mo (4.6, 26.1). T cell (ELIspot) IR occurred in 14/31 pts Arm C+A vs 3/22 pts Arm A. Antibody (Ab) (ELISA) IR occurred in 16/32 pts Arm C+A vs 0/27 Arm A. In Arm A+C subjects with induced T cells mOS NR (13.4, NR) vs without T cell induction, mOS 10.5 mo (3.9, 18.6) [p value 0.0003]. In Arm A, subjects with T cell IR mOS NR (10.3, NR) vs subjects without induction mOS 26.1 mo (15.4, 26.5) [p value 0.6585]. In Arm A+C subjects with Ab IR mOS 24.9 mo (10.1, NR) versus subjects without induction mOS 9.3 mo (5.0, 21.0) [p value 0.0278] No induction of Ab IR demonstrated in Arm A.