@article{332642bfeb6440a69db35101fe8c6f7d,
title = "A Phase 1b Study Evaluating the Safety, Tolerability, and Immunogenicity of CMB305, a Lentiviral-Based Prime-Boost Vaccine Regimen, in Patients with Locally Advanced, Relapsed, or Metastatic Cancer Expressing NY-ESO-1",
abstract = "Preclinical data suggest that a “prime-boost” vaccine regimen using a target-expressing lentiviral vector for priming, followed by a recombinant protein boost, may be effective against cancer; however, this strategy has not been evaluated in a clinical setting. CMB305 is a prime-boost vaccine designed to induce a broad anti-NY-ESO-1 immune response. It is composed of LV305, which is an NY-ESO-1 expressing lentiviral vector, and G305, a recombinant adjuvanted NY-ESO-1 protein. This multicenter phase 1b, first-in-human trial evaluated CMB305 in patients with NY-ESO-1 expressing solid tumors. Safety was examined in a 3 + 3 dose-escalation design, followed by an expansion with CMB305 alone or in a combination with either oral metronomic cyclophosphamide or intratumoral injections of a toll-like receptor agonist (glucopyranosyl lipid A). Of the 79 patients who enrolled, 81.0% had sarcomas, 86.1% had metastatic disease, and 57.0% had progressive disease at study entry. The most common adverse events were fatigue (34.2%), nausea (26.6%), and injection-site pain (24.1%). In patients with soft tissue sarcomas, a disease control rate of 61.9% and an overall survival of 26.2 months (95% CI, 22.1–NA) were observed. CMB305 induced anti-NY-ESO-1 antibody and T-cell responses in 62.9% and 47.4% of patients, respectively. This is the first trial to test a prime-boost vaccine regimen in patients with advanced cancer. This approach is feasible, can be delivered safely, and with evidence of immune response as well as suggestion of clinical benefit.",
keywords = "G305, LV305, NY-ESO-1, immunotherapy, lentivirus, myxoid liposarcoma, prime-boost, synovial sarcoma, vaccine",
author = "Neeta Somaiah and Chawla, {Sant P.} and Block, {Matthew S.} and Morris, {John C.} and Khanh Do and Kim, {Joseph W.} and Mihaela Druta and Sankhala, {Kamalesh K.} and Patrick Hwu and Jones, {Robin L.} and Sacha Gnjatic and Seunghee Kim-Schulze and Kevin Tuballes and Mahlet Yishak and Hailing Lu and Adam Yakovich and {Ter Meulen}, Jan and Michael Chen and Kenney, {Richard T.} and Chet Bohac and Pollack, {Seth M.}",
note = "Funding Information: NS reports support from Immune Design during the conduct of the study and a grant from Merck & Co. outside the submitted work. SC reports grants from Amgen, Roche, Threshold Pharmaceuticals, Immune Design, and Karyopharm Therapeutics outside the submitted work. MB reports institutional support from Immune Design and Merck & Co. during the conduct of the study, and grants from Bristol Myers Squibb, Genentech, Pharmacyclics, Marker Therapeutics, and Transgene SA outside the submitted work. JK reports support from Immune Design during the conduct of the study. MD reports receipt of consultation fees from Adaptimmune Therapeutics, Daiichi Sankyo, Epizyme, Blueprint Medicines, and Deciphera Pharmaceuticals outside of the submitted work. PH reports personal fees from Immatics, Dragonfly Therapeutics, GSK, and Sanofi outside of the submitted work. RJ reports grants/research support from MSD and GSK and receipt of consultation fees from Adaptimmune Therapeutics, Athenex, Blueprint Medicines, Clinigen, Eisai, Epizyme, Daichii Sankyo, Deciphera Pharmaceuticals, Immune Design, Lilly, Merck & Co., Pharma Mar S.A., and UpToDate. SG reports research funding from Immune Design during the conduct of the study; consultancy/advisory roles from Merck & Co. and OncoMed and research funding from Regeneron Pharmaceuticals, Genentech, Pfizer, and Takeda Pharmaceutical Company outside of the submitted work; and a patent for NY-ESO-1 peptides issued to GSK. The Human Immune Monitoring Center received support from Cancer Center P30 grant CA196521. HL was a full-time employee of Immune Design with stock options during the conduct of the study. AY was an employee and shareholder of Immune Design during the conduct of the study. JtM was a full-time employee and shareholder of Immune Design during the conduct of the study, and has patents US20160058852 (Immunotherapy of cancer through combination of local and systemic immune stimulation) and US20170196954 (Prime-boost regimens with a TLR4 agonist adjuvant and a lentiviral vector) pending with Merck & Co. MC was an employee of Immune Design during the conduct of the study. RK was an employee of Immune Design and subsequently employed by ClinReg Biologics, LLC as a consultant to Immune Design during the conduct of the study. CB was an employee of Immune Design during the conduct of the study and reports prior employment and current stock with Amgen and current employment and stock with Macrogenics, Inc. SP reports grants from Immune Design and Merck & Co. during the conduct of the study; grants from EMD Serono, Presage Biosciences, Janssen Pharmaceuticals, OncoSec, and Juno Therapeutics outside the submitted work; and personal fees from Daiichi Sankyo, GSK, and Blueprint Medicines outside the submitted work. The remaining authors ( JM, KD, KS, SKS, KT , and MY ) have nothing to disclose. Publisher Copyright: {\textcopyright} 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.",
year = "2020",
month = jan,
day = "1",
doi = "10.1080/2162402X.2020.1847846",
language = "English (US)",
volume = "9",
journal = "OncoImmunology",
issn = "2162-4011",
publisher = "Landes Bioscience",
number = "1",
}