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A phase 2 study of CMB305 and atezolizumab in NY-ESO-1+ soft tissue sarcoma: Interim analysis of immunogenicity, tumor control and survival

2017; Elsevier BV; Volume: 28; Linguagem: Inglês

10.1093/annonc/mdx387.007

1569-8041

Sant P. Chawla, Brian A. Van Tine, Seth M. Pollack, Kristen N. Ganjoo, Anthony Elias, Richard F. Riedel, Steven Attia, Edwin Choy, Scott H. Okuno, Mark Agulnik, Margaret von Mehren, Michael B. Livingston, Vicky L. Keedy, Claire F. Verschraegen, T Philip, Chet Bohac, Hailing Lu, M. Chen, Robert G. Maki,

CAR-T cell therapy research

Background: CMB305 is an active immunotherapy designed to generate and expand anti-NY-ESO-1 immune response (IR). CMB305 consists of a dendritic cell-targeting lentiviral vector encoding NY-ESO-1 (LV305), and a boost with an NY-ESO-1 recombinant protein plus GLA-SE (G305), a TLR-4 agonist. Phase 1 studies of LV305 and CMB305 showed this approach is safe, generates IR and appears to impact survival with 81% 1-yr survival in NY-ESO-1+ sarcoma patients (pts) following LV305 treatment. We evaluated efficacy and IR for combination of CMB305 (C) and atezolizumab (A) or A alone in NY-ESO-1+ synovial sarcoma (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 q6wk up to one year) + A (1200mg IV q3wk) vs. A alone in locally advanced or metastatic NY-ESO-1+ SS/MRCL. Primary endpoints are progression free survival (PFS) and overall survival (OS) with secondary endpoints of safety, IR, and response rate. Results: As of December 30, 2016, 58 patients were enrolled. A prespecified interim analysis of PFS included the first 36 pts with median 7.0 mos follow up (Arm A+C: median age 47 yrs, 78% SS, 100% metastatic, 78% = >2 chemotherapy; Arm A: median age 44 yrs, 56% SS, 67% metastatic, 56% = >2 chemotherapy). Combination A+C was well tolerated. Clinical benefit was similar between arms (Arm A+C: 8/18 pts with SD, 1 pt unconfirmed PR, 6 mos PFS rate 17%; Arm A: 10/18 pts SD, 6 mos PFS rate 22%). In addition, anti-NY-ESO-1 IR seen in 10/19 (53%) pts Arm A+C vs. 3/12 (25%) pts Arm A by T Cell ELISpot, and 9/22 (41%) pts Arm A+C vs. 0% Arm A by antibody ELISA. Pts with IR had target lesion increase of 2% compared to 18% in pts without IR based on preliminary ANOVA-model based analysis. No deaths observed in pts with induced anti-NY-ESO-1 T cell IR (0/13 deaths IR+ pts vs. 5/18 deaths IR- pts). Conclusions: In the interim analysis, Arm A+C resulted in a higher level of anti-NY-ESO-1 IR when compared to Arm A; pts with IR tend to have better target lesion control. Early data indicate that induction of anti-NY-ESO-1 IR may be associated with better survival. Clinical trial identification: NCT02609984 First received: November 14, 2015 Last updated: February 28, 2017 Last verified: December 2016 Legal entity responsible for the study: Immune Design Funding: Immune Design Disclosure: S. Chawla: Board of Directors/Stock: Prana, Uptick Health, Counterpoint Biomedical. Honoraria: Amgen, Threshold, Cytrx, Pharmamar, J&J, Tracon, Morphetek. Research project: Amgen, Threshold, Cytrx, Pharmamar, J&J, Tracon, Morphotek, BMS, Etsai, Immune Design. B.A. Van Tine: Stock ownership: none Membership on Advisory Board Novartis Lilly Janseen Epizyme Karyopharm Diiachi Board of Directors none Corporate sponsored research Pfizer Merck Speakers Beuro Caris Janseen Lilly. K. Ganjoo: Compensation to author for Advisory board with both Daiichi Sanko and Novartis. R.F. Riedel: Sponsored Research/Advisory Board: AADi, Arog, Daiichi-Sankyo, Karyopharm, Lilly, Novartis, Oncternal, Plexxikon, SARC, Threshold, Tracon, Tokalas. Eisai, EMD-Serono, Ignyta, Immune Design, Janssen. Consultant: Lilly, The Oncology Consortium. S. Attia: Compensation (to Mayo Clinic) as Principal Investigator from: AB Science, Morphotek, Threshold Pharmaceuticals, Tracon Pharma, ZioPharm, CytRX, Bayer, Novartis, Daichii, Bayer, Lilly, Immune Design, Karyopharm Therapeutics, Epizyme. E. Choy: Consulting fees from Amgen, EMD Serono, Daiichi, Bayer. M. Agulnik: Advisory board: Novartis, Janssen, Eisai and Lilly. V. Keedy: Consultant Karyopharm Janssen Research funding to institution for sponsored research: Lilly, Plexxicon, CytRx, Daiichi, Threshold, Janssen, Roche, Astrazeneca, MedPacto, Immune Design, GSK. T. Philip: Consultant: Novartis. C. Bohac: Employed by Immune Design. Stock ownership with Amgen, Immune Design H. Lu: Employee of Immune Design and Stock ownership Immune Design. M. Chen: Employee of Immune Design and Stock Ownership Immune Design. R. Maki: Clinical Trial support (institution), consulting fees, travel: Immune Design. All other authors have declared no conflicts of interest.