Prospective, randomized, placebo-controlled phase 2b trial of SurVaxM plus adjuvant temozolomide in newly diagnosed glioblastoma (SURVIVE).

Abstract

TPS2106 Background: Survivin is widely expressed in glioblastoma (GBM) and is implicated in tumor cell survival and treatment resistance, supporting survivin-targeted immunotherapy in newly diagnosed disease. The survivin long-peptide conjugate vaccine SVN53-67/M57-KLH (SurVaxM) has shown feasibility, immunogenicity, an acceptable safety profile and promising efficacy, in phase 1 and 2 trials in newly diagnosed GBM. We hypothesize that SurVaxM combined with standard adjuvant temozolomide (TMZ) post chemo radiation will improve outcomes in newly diagnosed GBM and that correlative biomarkers will define patient selection. Methods: SURVIVE is a prospective, randomized, double-blind, placebo-controlled, multicenter phase 2b trial evaluating SVN53-67/M57-KLH plus standard adjuvant TMZ versus placebo plus standard adjuvant TMZ in adults with newly diagnosed GBM. Patients are randomized 3:2 to investigational vaccine (Arm A) or placebo (Arm B), with stratification by Karnofsky performance status, MGMT promoter methylation status, and IDH status. Study intervention consists of four priming SurVaxM injections administered every 2 weeks followed by maintenance dosing every 8 weeks, administered alongside standard adjuvant TMZ (5 days every 28-day cycle; typically, 6-12 cycles per standard practice). The vaccine regimen is delivered as a survivin peptide conjugate with immunologic adjuvants; blinding is maintained via matched placebo injections. MRI surveillance is performed per protocol to support response assessment and the planned imaging correlatives. Key eligibility criteria include age ≥18 years; Karnofsky performance status ≥70; pathologically confirmed cerebral GBM meeting 2021 WHO criteria with available MGMT and IDH status; gross-total or near-total resection with minimal residual enhancement on immediate postoperative MRI (≤72 hours); completion of chemoradiation with ≥75% of planned concurrent temozolomide; no evidence of progression on post-chemoradiation MRI; randomization within approximately 16–18 weeks of resection; and dexamethasone ≤4 mg/day at enrollment. The planned evaluable sample size is 228 patients (n=137 Arm A; n=91 Arm B). The primary analysis will be conducted in the intention-to-treat population using a two-sided alpha of 0.05, with stratified time-to-event comparisons to account for key baseline factors. The alternate hypothesis assumes a 1-year survival rate of 75% in the SurVaxM group (Arm A; comparable to a median overall survival (mOS) of 29 months assuming an exponential distribution) and 60% in the control group (Arm B; comparable to a mOS of 16 months assuming an exponential distribution). Clinical trial information: NCT05163080 .