CureVac presents data from dose-escalation Part A of Phase 1 CVGBM vaccine study

CureVac presented data from the dose-escalation Part A of its ongoing Phase 1 CVGBM cancer vaccine study in patients with glioblastoma at the European Society for Medical Oncology Congress. The presented data include safety, tolerability and initial immunogenicity data provided for all evaluable patients treated within Part A of the trial with CVGBM dose levels of 12-100 microgram.In this highly aggressive and challenging cancer indication, preliminary immunogenicity results demonstrate that treatment with CVGBM-only following chemo-radiation therapy successfully induces cancer antigen-specific T-cell responses in 77% of evaluable patients. Most notably, within the group of responding patients, 84% of immune responses were generated de novo by the CVGBM vaccination, inducing T-cell activity in patients who had no pre-existing T-cell activity against the encoded antigens. While CD8+ T-cells primarily attack and destroy cancer cells, CD4+ T-cells play a critical role in coordinating the immune response and supporting the activity of CD8+ T-cells over time. The majority of responding patients showed cancer antigen-specific CD8+ responses, 31% of responding patients had CD4+ responses and 23% had both a CD8+ and a CD4+ response. Immune activation was accompanied by a favorable safety and tolerability profile, with no dose-limiting toxicities observed up to and including the highest tested dose of 100 microgram, as confirmed by an independent Data and Safety Monitoring Board. The majority of treatment-related adverse events were reported as grade 1 and grade 2 systemic reactions characteristic to mRNA-based therapeutics. These included headache, chills, fever and fatigue, which resolved within 1-2 days following the injection. Seven patients reported a total of nine grade 3 TRAEs, of which four were classified as serious adverse events. No grade 4 or 5 adverse events occurred. Correspondingly, a 100 microgram dose was selected as the recommended dose for the already initiated dose-confirmation Part B of the study. The open-label study is evaluating the safety and tolerability of CVGBM in HLA-02:01-positive patients with newly diagnosed and surgically resected MGMT-unmethylated glioblastoma or astrocytoma with a molecular signature of glioblastoma. CVGBM replaces the temozolomide maintenance phase. It is administered as a monotherapy after surgical resection and completion of radiotherapy with or without chemotherapy. The study consists of two parts, a dose-escalation part and a dose-expansion part. In the fully enrolled Part A, patients received seven intramuscular vaccinations at escalating doses in the range of 12 to 100 microgram on days 1, 8, 15, 29, 43, 57 and 71 and optional maintenance vaccinations in case of non-progression or potential benefit. 16 patients were enrolled, of which 13 were evaluable for immune responses. All patients completed surgery, 44% with complete tumor resection and 56% with only partial resection followed by chemo-radiation with temozolomide. Antigen-specific CD4+ and CD8+ T-cell responses were assessed at relevant pre-determined timepoints until day 99. Part B of the study is currently ongoing at the recommended dose of 100 microgram.