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

NCT04943848 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: LCH 20C05
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Diffuse Intrinsic Pontine Glioma; Diffuse Midline Glioma, H3 K27M-Mutant

Keywords

Immunotherapy; Cancer vaccine; Checkpoint blockade; DIPG; Diffuse intrinsic pontine glioma; High grade glioma; DMG; Diffuse midline glioma; rHSC-DIPGVax; Balstilimab; Zalifrelimab

Outcome Measures

Primary Outcomes (3)

• Safety and Tolerability: Dose limiting toxicities of rHSC-DIPGVax

  Number of DLT's per CTCAE version 5.0 and iRANO guidelines.

  DLT period of 28 days for rHSC-DIPGVax monotherapy

• Safety and Tolerability: Dose limiting toxicities of rHSC-DIPGVax plus BALSTILIMAB

  Number of DLT's per CTCAE version 5.0 and iRANO guidelines.

  DLT period of 28 days for Part A

• Safety and Tolerability: Dose limiting toxicities of rHSC-DIPGVax plus BALSTILIMAB and ZALIFRELIMAB

  Number of DLT's per CTCAE version 5.0 and iRANO guidelines.

  DLT period of 42 days for Part B

Secondary Outcomes (4)

• Total number of DLT's for ZALIFRELIMAB at RP2D in combination with rHSC-DIPGVax and BALSTILIMAB

  On-going during 1 year of therapy plus 3 month follow up

• To evaluate the efficacy of the combination of rHSC-DIPGVax, BALSTILIMAB, and ZALIFRELIMB in pediatric subjects with DIPG and DMG as measured by overall survival at 12 months and time-to-progression as measured from time of diagnostic imaging

  On-going during 1 year of therapy plus 3 month follow up

• Overall survival at 1 year

  On-going during 1 year of therapy

• Time to progression

  On-going during 1 year of therapy plus up to 5 years off treatment

Other Outcomes (4)

• To evaluate biologic correlates for immune response in order to assess neo-antigen specific T cell responses

  At the end of each cycle (1 cycle = 28 days) fore the first 3 cycles, on day 1 of cycle 6, and at 3 month post treatment follow up

• To characterize PK profile (Cmax) of BALSTILIMAB as a mAb monotherapy with rHSC-DIPGVax and in mAb combination with ZALIFRELIMAB and rHSC-DIPGVax to assess potential impact on PK exposure and biologic activity in pediatrics

  1 cycle = 28 days; Predose Cycle 1 day 1, 2 hours post dose 1, cycle 1 day 2, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 predose and 2 hours post dose, cycle 4 day 2, cycle 4 day 8, cycle 5 day 1, cycle 10 day 1, cycle 15 day 1, and end of treatment

• To characterize PK profile (AUC) of BALSTILIMAB as a mAb monotherapy with rHSC-DIPGVax and in mAb combination with ZALIFRELIMAB and rHSC-DIPGVax to assess potential impact on PK exposure and biologic activity in pediatrics

  1 cycle = 28 days; Predose Cycle 1 day 1, 2 hours post dose 1, cycle 1 day 2, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 predose and 2 hours post dose, cycle 4 day 2, cycle 4 day 8, cycle 5 day 1, cycle 10 day 1, cycle 15 day 1, and end of treatment

Study Arms (4)

"Lead In": rHSC-DIPGVax Monotherapy

EXPERIMENTAL

rHSC-DIPGVax for 8 total doses

Biological: rHSC-DIPGVax

Part A: rHSC-DIPGVax in Combination with BALSTILIMAB (Anti-PD1)

EXPERIMENTAL

rHSC-DIPGVax (8 total doses) + BALSTILIMAB (1 year of therapy or 27 cycles, whichever comes first) Patients will enroll 6-10 weeks post standard of care (SOC) radiation completion. Steroid dose must be at or below 0.5mg/kg/day for a minimum of 7 days. The first 3 patients must be 5 years or older to 18. Subsequently, subjects ages 12 months to 18 years can be enrolled. Up to six patients will be enrolled on Part A. Once safety is established for rHSC-DIPGVax plus anti-PD1 (BALSTILIMAB), the study will proceed to Part B.

Biological: rHSC-DIPGVax; Drug: Balstilimab

Part B: Dose Escalation of ZALIFRELIMAB (Anti-CTLA4)

EXPERIMENTAL

rHSC-DIPGVax (8 total doses) + BALSTILIMAB + ZALIFRELIMAB (1 year of therapy or 9 cycles, whichever comes first) Patients will enroll 6-10 weeks post standard of care (SOC) radiation therapy. Steroid dose must be at or below 0.5mg/kg/day for a minimum of 7 days. The first 3 patients must be 5 years or older to 18. Subsequently, subjects ages 12 months to 18 years can be enrolled. Up to 12 patients will be enrolled on Part B. Once safety is established for rHSC-DIPGVax plus anti-PD1 (BALSTILIMAB) plus anti-CTLA4 (ZALIFRELIMAB), the study will proceed to Part C.

Biological: rHSC-DIPGVax; Drug: Balstilimab; Drug: Zalifrelimab

Part C: Dose Expansion

EXPERIMENTAL

rHSC-DIPGVax (8 total doses) + BALSTILIMAB + ZALIFRELIMAB (at RP2D from Part B) (1 year of therapy or 9 cycles, whichever comes first) Patients will enroll 6-10 weeks post standard of care (SOC) radiation therapy. Steroid dose must be at or below 0.5mg/kg/day for a minimum of 7 days. Up to 12 patients will be enrolled on Part C. All subjects in Part C will be monitored for DLT's for the duration of their participation in the study to monitor for excess toxicity.

Biological: rHSC-DIPGVax; Drug: Balstilimab; Drug: Zalifrelimab

Interventions

Balstilimab DRUG

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

Also known as: checkpoint blockade, anti-PD1

Part A: rHSC-DIPGVax in Combination with BALSTILIMAB (Anti-PD1); Part B: Dose Escalation of ZALIFRELIMAB (Anti-CTLA4); Part C: Dose Expansion

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)

Also known as: checkpoint blockade, anti-CTLA4

Part B: Dose Escalation of ZALIFRELIMAB (Anti-CTLA4); Part C: Dose Expansion

rHSC-DIPGVax BIOLOGICAL

Off-the-shelf, neoantigen heat shock protein vaccine

Also known as: vaccine

"Lead In": rHSC-DIPGVax Monotherapy; Part A: rHSC-DIPGVax in Combination with BALSTILIMAB (Anti-PD1); Part B: Dose Escalation of ZALIFRELIMAB (Anti-CTLA4); Part C: Dose Expansion

Eligibility Criteria

• Age: 12 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ann & Robert H Lurie Children's Hospital of Chicago: lead
• Dana-Farber Cancer Institute: collaborator
• Children's Hospital of Orange County: collaborator
• University of Calgary: collaborator

Study Sites (3)

Children's Health Orange County (CHOC)

Orange, California, 92868, United States

RECRUITING

Ann and Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

RECRUITING

Dana-Farber Boston Children's Cancer and Blood Disorders Center

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma; Glioma

Interventions

Vaccines; balstilimab; Immune Checkpoint Inhibitors; spartalizumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ashley Plant-Fox, MD

  Ann and Robert H. Lurie Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Monica Newmark, BS, RN

CONTACT

312-227-4847; MNewmark@luriechildrens.org

Ashley Plant-Fox, MD

CONTACT

312-227-4858; aplant@luriechildrens.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase I, open label, plus expansion clinical trial

Study Record Dates

• First Submitted: May 24, 2021
• First Posted: June 29, 2021
• Study Start: January 10, 2022
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)