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).
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.
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).
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
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.