A multicenter, randomized controlled phase 2b trial of survivin vaccine SurVaxM plus adjuvant temozolomide for newly diagnosed glioblastoma (SURVIVE).

Document Type

Conference Proceeding

Publication Date

5-29-2024

Publication Title

Journal of Clinical Oncology

Abstract

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.

Volume

42

Issue

16_suppl

First Page

TPS2099-TPS2099

Comments

Society for Neuro-Oncology (SNO).November 21-24, 2024. Houston, Texas.

DOI

10.1200/JCO.2024.42.16_suppl

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