IMMU-03. MULTICENTER RANDOMIZED PLACEBO CONTROLLED PHASE III TRIAL OF AN AUTOLOGOUS FORMALINFIXED TUMOR VACCINE (CELLM-001) FOR NEWLY DIAGNOSED GLIOBLASTOMAS

The development of novel treatments for glioblastoma is desired and immunotherapy is theoretically expected for highly invasive glioblastoma. An autologous formalin-fixed vaccine (AFTV) derived from resected tumor tissue is stable, contains multiple tumor peptides, and could induce specific immunity. We have conducted three clinical trials in patients with glioblastoma, and the most recent trial was a double-blind, multicenter, phase IIb trial with 63 case enrollments. Although this Phase IIb study revealed no vaccine effects in the whole cohort (mOS: 25.6 months of AFTV group, 31.5 months of the placebo group), the 3-year PFS for patients with total tumor removal was 81% in the AFTV group versus 46% in the placebo group (P=0.067). AFTV vaccine (Cellm-001) may have an effect on certain patient subgroups, and a Phase III study has started in November 2021 (jRCT2031200153). Based on Phase IIb, the enrolled patients were those who could be completely resected on MRI. Cellm-001 administration to a patient in the placebo group at recurrence (crossover) was prohibited. In addition, photodynamic therapy (PDT) was added as a stratification factor because our retrospective study showed a good prognosis of 19 patients who underwent both PDT and AFTV (mOS 47.7 months).

Trial design: double-blind (1: 1), phase III multicenter, registration 4 years, observation 2 years. ESTIMATED ENROLLMENT: 112 patients with primary glioblastoma (18-75 years old) whose contrast-enhanced lesion could be completely removed on the image and who received standard local radiotherapy and temozolomide chemotherapy. STRATIFICATION FACTORS: presence or absence of PDT, age, KPS. ADMINISTRATION METHOD: Intradermal administration 3 times before radiochemotherapy and 6 times in parallel with maintenance chemotherapy after completion. PRIMARY ENDPOINT: OS, secondary endpoints: PFS and adverse events. https://jrct.niph.go.jp/en-latest-detail/jRCT2031200153.

An investigator-initiated phase III trial will investigate the efficacy and safety of unique AFTV immunotherapy.