P07.09.b a randomized phase 2b study of survivin vaccine survaxm plus adjuvant temozolomide for newly-diagnosed glioblastoma (survive)

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) showed that a 15-amino acid-peptide-conjugate vaccine (SurVaxM) stimulates the production of survivin-directed antibodies and anti-tumor CTL in nGBM patients, resulting in a median OS of 25.9 months. This Phase 2b randomized controlled trial (RCT) aims to further investigate the efficacy 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 15 sites. Included patients have age ≥18 years, normal organ function, Karnofsky Performance Status (KPS) ≥70, surgical resection, 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 the median OS in early phase trials, and 60% in the control arm, the study will enroll 265 patients, 159 in arm A and 106 in arm B. 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. The study is expected to take 35 months, with ongoing accrual. RESULTS 69 patients have been enrolled as of April 11, 2023. CONCLUSION Findings from this trial will demonstrate the safety and efficacy of survivin vaccine in GBM (Clinical trial information: NCT05163080).