A multicenter, randomized controlled phase 2b trial of survivin vaccine SurVaxM plus adjuvant temozolomide for newly diagnosed glioblastoma (SURVIVE).
Year: 2024
Type: conference-abstract
Abstract: TPS2099 Background: Newly-diagnosed glioblastoma (nGBM) has a dismal prognosis with a median overall survival (OS) of nearly 16 months. nGBM cells have high expression of tumor-associated survivin protein. Survivin, localized to the cell surface through presentation by MHC class I molecules, is recognized by antibodies and cytotoxic T-lymphocytes (CTLs). A phase 2a trial (NCT02455557) demonstrated a median OS of 25.9 months in nGBM from a 15-amino acid-peptide-conjugate vaccine (SurVaxM), which also stimulated production of survivin-directed antibodies and anti-tumor CTL. This phase 2b randomized controlled trial (RCT) aims to further investigate the efficacy and safety of SurVaxM and adjuvant temozolomide for nGBM. Methods: This multicenter, placebo-controlled, investigator- and patient-blinded, in-progress RCT randomizes nGBM patients receiving standard of care to either SurVaxM (arm A) or saline placebo (arm B) in a 3:2 ratio at 11 sites. Included patients have age ≥18 years, normal organ function, Karnofsky Performance Status (KPS) ≥70, receiving surgical resection with residual MRI contrast enhancement of ≤1 cm3 within 72 hours of resection, and adjuvant temozolomide (TMZ) therapy. Patients with recurrent, multicentric, brainstem- or cerebellar-origin GBM are excluded, as well as patients on tumor-treating fields or other immunotherapies. All patients undergo 3 phases: (1) vaccine priming (VP) phase, starting within 4 weeks after completion of chemoradiation, where 4 doses of SurVaxM or Placebo are administered every 2 weeks; (2) adjuvant TMZ phase, started after ≥1 VP dose; and (3) vaccine maintenance phase, started 8 weeks after VP, with SurVaxM or placebo given every 8 weeks. TMZ phase overlaps with VP and VM phases. The primary endpoint is median OS. Assuming a 1-year survival rate of 75% in the SurVaxM arm, comparable to median OS in early phase trials, and 60% in the control arm, the required sample size consists of 137 in the SurVaxM arm and 91 in the control arm for a total sample size of 228. Accounting for dropout, the study aims to enroll 246 patients. A log-rank test stratified by KPS (70-80 and 90-100), MGMT status (methylated and unmethylated), and IDH status (mutant and wild-type) will be used for analysis. Secondary endpoints per study arm are survival at 15, 18, and 24 months, median progression-free survival, toxicity, and progression-free survival at 3, 6, and 12 months. A single sequential OS-driven interim analysis is planned when 50% of OS events (deaths) occur. 205 patients have been enrolled as of January 2024. Clinical trial information: NCT05163080 .
Source: Journal of Clinical Oncology
Authors: Manmeet Singh Ahluwalia, Michael J Ciesielski, David A. Reardon, Nicholas A. Butowski, Robert Aiken, Vyshak Venur, Ajay Prakash Abad, Laszlo Mechtler, David M. Peereboom, Yazmin Odia, Kaylyn Sinicrope, John A Boockvar, Andrew J. Brenner, Marissa Barbaro, Ahmad Ozair, Ahmed Belal, Jing-Xin Qiu, Atulya Aman Khosla, Danielle M. Casucci, Robert Alan Fenstermaker
Institutions: Baptist Hospital of Miami, Baptist Health South Florida, Roswell Park Comprehensive Cancer Center, Center for Neuro-Oncology, Dana-Farber Cancer Institute, University of California, San Francisco, Overlook Medical Center, University of Washington, Cleveland Clinic, The University of Texas MD Anderson Cancer Center, Northwell Health, Lenox Hill Hospital, The University of Texas at San Antonio Health Science Center, NYU Langone Health, Beaumont Health, Beaumont Hospital, Royal Oak
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4400522269