440O - First in human study of the mRNA-based cancer vaccine CVGBM in patients (pts) with newly diagnosed and surgically resected MGMT-unmethylated glioblastoma (GBM): First results from the dose escalation phase

Background

CVGBM is an investigational therapeutic mRNA-based vaccine encoding 8 epitopes derived from tumor associated antigens with potential relevance in GBM. We report first results from an ongoing, first-in-human study evaluating the safety of CVGBM in pts with newly diagnosed MGMT-unmethylated GBM.

Methods

HLA-A*02:01-positive pts with newly diagnosed MGMT-unmethylated GBM (CNS WHO Grade [Gr] 4) who had a gross total or partial resection and completed radiotherapy ± concomitant temozolomide received CVGBM on Days 1, 8, 15, 29, 43, 57 and 71 + 6 optional doses at 6-week intervals. Primary endpoints are safety, tolerability and dose-limiting toxicities (DLTs). Immunogenicity is an exploratory endpoint. This study consists of a dose-escalation part (Part A) and a dose-expansion part (Part B). We report results from Part A for dose levels (DLs) of 12-100 μg.

Results

As of 29 Feb 2024, 16 pts were enrolled; 3 each in DL 1 (12 μg), DL 2 (25 μg), and DL 3 (50 μg), and 7 in DL 4 (100 μg). For all cohorts, mean time on study from 1st dose to last visit was 4.5 months (min: 1.5; max: 8). 109 doses were administered (mean: 6.8 doses per pt). All pts completed the 2-week DLT evaluation period without DLTs. Of 156 treatment-emergent adverse events (TEAEs), the majority (73%) were Common Toxicity Criteria Gr 1 (21% Gr 2, 6% Gr 3). The most common related TEAEs were chills (n=13), pyrexia (n=12), headache (n=12), fatigue (n=11) and malaise (n=5), mostly of mild to moderate severity. 7 pts had 9 ≥ Gr 3 AEs assessed as potentially related to CVGBM by the investigators outside the DLT period (cerebral edema [n=2], and leukoencephalopathy, pseudoprogression with cerebral edema, structural epilepsy, ataxia, hypertension, malaise and fever [1 of each]), evenly distributed across cohorts. Continuous monitoring of their clinical course is ongoing. First immunogenicity data are planned to be presented.

Conclusions

CVGBM was generally well tolerated with an acceptable safety profile. The highest tolerated dose was not reached. Based on all available safety data, the selected dose for trial expansion was 100 μg.

Clinical trial identification

NCT05938387.

Editorial acknowledgement

Medical writing assistance was provided by Mark English, PhD, of CureVac SE.

Legal entity responsible for the study

CureVac SE.

Funding

CureVac SE.

Disclosure

G. Tabatabai: Financial Interests, Institutional, Funding: University Hospital Tübingen ; Financial Interests, Institutional, Advisory Board: Bayer, Boehringer Ingelheim, CureVac SE, Miltenyi Bionedicine, Novocure; Financial Interests, Institutional, Steering Committee Member: Bayer, Novocure; Financial Interests, Institutional, Invited Speaker: Novocure, Servier. P. Freres: Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, Astellas Pharma, Janssen; Financial Interests, Personal, Advisory Role: Astellas Pharma BV, Pfizer; Financial Interests, Personal, Advisory Role, Travel, accomodation, expenses: Merck; Financial Interests, Personal, Advisory Board, Travel, accomodation, expenses: Astellas, Janssen, MSD. M. Glas: Financial Interests, Personal, Other, Honoraria: NovoCure, Janssen-Cilag, Merck, Seagen; Financial Interests, Personal, Advisory Role: Novocure; Financial Interests, Personal, Advisory Board: Servier, Seagen, Novartis; Financial Interests, Personal, Research Funding: Novocure; Financial Interests, Personal, Other, Travel, accomodations, expenses: Novocure, Janssen-Cilag. C. Seidel: Financial Interests, Personal, Other, Honoraria: Seagen; Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Personal, Research Funding: Seagen; Financial Interests, Personal, Other, Travel, accomodations, expenses: Seagen. U. Herrlinger: Financial Interests, Personal, Advisory Board: Medac, Bayer; Financial Interests, Personal, Invited Speaker: Medac, Bayer. B. Neyns: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Novartis, Merck Sharp & Dohme, Pierre Fabre; Financial Interests, Personal, Research Funding: Novartis; Financial Interests, Personal, Other, Travel, accomodation, expenses: Merck Sharp and Dohme, Pierre Fabre. M.H. Falk: Financial Interests, Personal, Full or part-time Employment: CureVac SE. L.L. de Freitas Chama: Financial Interests, Personal, Full or part-time Employment: CureVac SE. P.G. Kelemen: Financial Interests, Personal, Full or part-time Employment: CureVac SE; Financial Interests, Personal, Stocks or ownership: CureVac SE; Financial Interests, Personal, Proprietary Information: MorphoSys AG. F. Schwenke: Financial Interests, Personal, Full or part-time Employment: CureVac SE. S.D. Koch: Financial Interests, Personal, Full or part-time Employment: CureVac SE; Financial Interests, Personal, Stocks/Shares: CureVac SE, Gritstone Bio, NovoNordisk, Moderna, Biontech, Vivoryon, Pfizer; Financial Interests, Institutional, Research Funding: CureVac SE; Financial Interests, Personal, Other, Travel, accomodation, expenses: CureVac SE. P. Romer Roche: Financial Interests, Personal, Full or part-time Employment: CureVac SE; Financial Interests, Personal, Stocks/Shares: CureVac SE. U.S. Gnad-Vogt: Financial Interests, Personal, Full or part-time Employment: CureVac SE; Financial Interests, Personal, Leadership Role: CureVac SE; Financial Interests, Personal, Stocks/Shares: CureVac SE, Bristol Myers Squibb, Bavarian Nordic, Biontech; Financial Interests, Personal, Other, Honoraria: CureVac SE; Financial Interests, Personal, Advisory Role: CureVac SE; Financial Interests, Personal, Speaker’s Bureau: CureVac SE; Financial Interests, Personal, Proprietary Information: CureVac SE; Financial Interests, Personal, Other, Travel, accomodations, expenses: CureVac SE. All other authors have declared no conflicts of interest.