NCT04749641: ENACTING

Neoantigen Vaccine Therapy Against H3.3-K27M Diffuse Intrinsic Pontine Glioma

Completed Phase 1 Last updated 6 June 2025

What this trial tests

Phase 1 trial testing Histone H3.3-K27M Neoantigen Vaccine Therapy in Diffuse Intrinsic Pontine Glioma in 16 participants. Completed in 14 October 2024.

Timeline

8 March 2021

Primary endpoint
14 October 2024

14 October 2024

Quick facts

Lead sponsor	Yang Zhang
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	16
Start date	8 March 2021
Primary completion	14 October 2024
Estimated completion	14 October 2024
Sites	1 location across China

Drugs / interventions tested

• Histone H3.3-K27M Neoantigen Vaccine Therapy — full drug profile →

Conditions studied

• Diffuse Intrinsic Pontine Glioma — all drugs for Diffuse Intrinsic Pontine Glioma →

Sponsor

Yang Zhang — full company profile →

Who can join

5 and older, any sex, with Diffuse Intrinsic Pontine Glioma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Diffuse intrinsic pontine gliomas (DIPGs), which diffusely occupy the pons of brainstem, are the deadliest primary brain cancer in children. Biopsy for pathology plus radiotherapy remains the current standard-of-care treatment that is minimal effective. Thus, the median overall survival after diagnosis is just 10 months. Recent studies have identified a lysine 27-to-methionine (K27M) somatic mutation at histone H3 variant (H3.3), as a feature mutation in DIPGs. Several preclinical studies have already demonstrated H3.3-K27M as a promising target for immunotherapy. The researched vaccine is a cancer-treatment vaccine containing an H3.3-K27M targeted neoantigen peptide, that can be taken up by antigen-presenting cells (APCs). APCs can present the peptide with the major histocompatibility complex (MHC) molecules on cell surface, thereby activating neoantigen-specific T cells and triggering corresponding cytotoxic T cell immune responses to eliminate H3.3-K27M-expressing DIPG cells. The main goal of this study is investigating the safety and preliminary efficacy of the vaccine in treating newly-diagnosed DIPGs when the vaccine is administered in combination with the standard-of-care treatment.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Neoantigens: promising targets for cancer therapy.
   Xie N, Shen G, Gao W, Huang Z, et al · · 2023 · cited 713× · PMID 36604431 · DOI 10.1038/s41392-022-01270-x
2. Beyond Just Peptide Antigens: The Complex World of Peptide-Based Cancer Vaccines.
   Stephens AJ, Burgess-Brown NA, Jiang S. · · 2021 · cited 112× · PMID 34276688 · DOI 10.3389/fimmu.2021.696791
3. The intrinsic and microenvironmental features of diffuse midline glioma: Implications for the development of effective immunotherapeutic treatment strategies.
   Persson ML, Douglas AM, Alvaro F, Faridi P, et al · · 2022 · cited 58× · PMID 35481923 · DOI 10.1093/neuonc/noac117
4. Therapeutic cancer vaccines: From biological mechanisms and engineering to ongoing clinical trials.
   Sobhani N, Scaggiante B, Morris R, Chai D, et al · · 2022 · cited 57× · PMID 35759856 · DOI 10.1016/j.ctrv.2022.102429
5. Pediatric Diffuse Midline Gliomas: An Unfinished Puzzle.
   Di Ruscio V, Del Baldo G, Fabozzi F, Vinci M, et al · · 2022 · cited 34× · PMID 36140466 · DOI 10.3390/diagnostics12092064
6. Personalized Neoantigen-Pulsed DC Vaccines: Advances in Clinical Applications.
   Tang L, Zhang R, Zhang X, Yang L. · · 2021 · cited 34× · PMID 34381724 · DOI 10.3389/fonc.2021.701777
7. Neoantigens in precision cancer immunotherapy: from identification to clinical applications.
   Zhang Q, Jia Q, Zhang J, Zhu B. · · 2022 · cited 32× · PMID 35838545 · DOI 10.1097/cm9.0000000000002181
8. Clinical and Translational Advances in Glioma Immunotherapy.
   Bunse L, Bunse T, Krämer C, Chih YC, et al · · 2022 · cited 29× · PMID 36303101 · DOI 10.1007/s13311-022-01313-9