ATIM-14. ALLIANCE A071101: A PHASE II RANDOMIZED TRIAL COMPARING THE EFFICACY OF HEAT SHOCK PROTEIN PEPTIDE COMPLEX-96 (HSPPC-96) VACCINE GIVEN WITH BEVACIZUMAB VERSUS BEVACIZUMAB ALONE IN THE TREATMENT OF SURGICALLY RESECTABLE RECURRENT GLIOBLASTOMA

Abstract BACKGROUND Heat shock protein vaccines can be used to stimulate anti-tumor immune responses. An autologous vaccine (HSPPC-96) generated from patient resected tumors has been previously studied in single arm phase I/II trials for newly diagnosed and recurrent GBM. Based on promising survival in these studies, a randomized, multi-centered phase II trial of HSPPC-96 for recurrent GBM compared to bevacizumab was undertaken (NCT01814813). METHODS Patients with 1st/2nd recurrence of resectable GBM were enrolled and underwent surgery with generation of HSPPC-96 from autologous tumors. Post-operative eligibility included a volumetric extent of resection ≥90% (by central review) and sufficient tumor to generate a minimum of 4 vaccine doses. Patients were randomized (1:1:1) to receive HSPPC-96 vaccine followed by bevacizumab at subsequent progression vs. concurrent HSPPC-96 vaccine and bevacizumab vs. bevacizumab alone. The primary endpoint was overall survival (OS) aiming to detect a 36% reduction in HR with 85% power and alpha=0.1 for pooled HSPPC-96 groups vs. bevacizumab alone. Planned enrollment was 165 patients (n=55/arm). An interim analysis was pre-planned at 50% of events (65 deaths). Secondary endpoints included progression-free survival and adverse events. RESULTS At final analysis, 90 patients were enrolled with a distribution of 29:30:31. The study was terminated for futility after the interim analysis. In the intention to treat population, OS for the HSPPC-96 treated groups was 7.5 vs. 10.7 months for bevacizumab alone (HR=2.06 [95% CI 1.18–3.60], p=0.008). Among patients treated per protocol (n=73), OS for HSPPC-96 patients was 8.6 vs. 12.3 months (HR=1.99 [95% CI 1.03–3.81], p=0.03). Trends were similar for progression-free survival between groups. HSPPC-96 toxicity was well tolerated with no attributable serious adverse events. CONCLUSIONS The study failed to demonstrate a survival benefit for patients treated with HSPPC-96 alone or in combination with bevacizumab compared to bevacizumab alone. Correlative analyses are ongoing. SUPPORT: U10CA180882, U10CA180821, U10CA180868, U24CA196171

CODEL: Phase III study of RT, RT + Temozolomide (TMZ), or TMZ for newly-diagnosed 1p/19q Codeleted Oligodendroglioma. Analysis from the initial study design

BACKGROUND We report the analysis involving patients treated on the initial CODEL design. METHODS Adults (>18) with newly-diagnosed 1p/19q WHO grade III oligodendroglioma were randomized to RT (5940 cGy) alone (Arm A); RT with concomitant and adjuvant temozolomide (TMZ) (Arm B); or TMZ alone (Arm C). Primary endpoint was overall survival (OS), Arm A versus B. Secondary comparisons were performed for OS and progression-free survival (PFS), comparing pooled RT arms versus TMZ-alone arm. RESULTS Thirty-six patients were randomized equally. At median follow-up of 7.5 years, 83.3% (10/12) TMZ-alone patients progressed, versus 37.5% (9/24) on the RT arms. PFS was significantly shorter in TMZ-alone patients compared to RT-treated patients (HR=3.12; 95% CI: 1.26, 7.69; p=0.014). Death from disease progression occurred in 3/12 (25%) of TMZ-alone patients and 4/24 (16.7%) on the RT Arms. OS did not statistically differ between arms (comparison underpowered). After adjustment for IDH status (mutated/wildtype) in a Cox regression model utilizing IDH and RT treatment status as co-variables (Arm C vs pooled Arms A+B), PFS remained shorter for patients not receiving RT, (HR= 3.33; 95% CI: 1.31, 8.45; p=0.011), but not OS ((HR = 2.78; 95% CI 0.58, 13.22, p=0.20). Grade 3+ adverse events occurred in 25%, 42% and 33% of patients (Arms A, B, and C). There were no differences between Arms in neurocognitive decline comparing baseline to 3 months. CONCLUSIONS TMZ-alone patients experienced significantly shorter PFS than patients treated on the RT Arms. The ongoing CODEL trial has been redesigned to compare RT+PCV versus RT+TMZ