rHSC-DIPGVax Plus Checkpoint Blockade for the Treatment of Newly Diagnosed DIPG and DMG

Summary

This is a phase I, open label, plus expansion clinical trial evaluating the safety and tolerability of rHSC-DIPGVax in combination with BALSTILIMAB and ZALIFRELIMAB. rHSC-DIPGVax is an off-the-shelf neo-antigen heat shock protein containing 16 peptides reflecting neo-epitopes found in the majority of DIPG and DMG tumors. Newly diagnosed patients with DIPG and DMG who have completed radiation six to ten weeks prior to enrollment are eligible.

Interventions

• rHSC-DIPGVax · BIOLOGICAL

  Off-the-shelf, neoantigen heat shock protein vaccine

• Balstilimab · DRUG

  BALSTILIMAB is a human monoclonal antibody that targets programmed cell death 1 (PD1)

• Zalifrelimab · DRUG

  ZALIFRELIMAB is a human monoclonal immunoglobulin G1k subclass (IgG1k) antibody that specifically recognizes cytotoxic T lymphocyte-associated protein 4 (CTLA-4, also known as CD152)

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

Inclusion Criteria:

* Subjects with newly diagnosed typical or non-typical, biopsy-proven DIPG or DMG are eligible for study enrollment. Biopsy is not required for subjects with radiographically typical DIPG meeting imaging criteria. Biopsy is required for DMG's and non-radiographically typical DIPG. Histone mutation must be confirmed by pathology report. Radiographically typical DIPG defined as a tumor with a pontine epicenter and diffuse involvement of more than 2/3 of the pons.

  = Subjects ages \> or = to 12 months and \< or = 18 years ("Lead In", Part A, and Part B require first three patients be \> or = to 12 years of age)
* BSA \> or = 0.35m2 at the time of study enrollment
* Performance score: Karnofsky \>50% of subjects \>16 years of age and Lansky \> or = 50 for subjects \< or = 16 years of age. Subjects who are unable to walk because of paralysis but are up in a wheelchair will be considered ambulatory for the purpose of assessing the performance score.
* Must start radiation therapy within 42 days from date of diagnostic imaging. C1D1 must be within 42 days to 70 days post radiation (6-10 weeks). Patients CANNOT receive temozolomide during radiation
* Corticosteroids should be weaned as tolerated after radiation therapy with the goal of \< or = 0.5mg/kg/day for a minimum of 7 days prior to enrollment.
* Subjects must have measurable disease

Exclusion Criteria:

* Patients cannot receive temozolomide during radiation
* Disseminated disease
* Subjects who have received any cancer therapy except for radiation
* Autoimmune or immune disorders
* Active respiratory disorder or infection
* Active viral infection

Sites (3)

• Children's Health Orange County (CHOC), Orange, California · RECRUITING
• Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois · RECRUITING
• Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts · RECRUITING