rHSC-DIPGVax Plus Checkpoint Blockade for the Treatment of Newly Diagnosed DIPG and DMG
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age12-18
SponsorAnn & Robert H Lurie Children's Hospital of Chicago
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
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
Disqualifiers
Patients cannot receive temozolomide during radiation
Disseminated disease
Subjects who have received any cancer therapy except for radiation
Autoimmune or immune disorders
Trial design
Design model
Sequential
Treatments tested in this trial
rHSC-DIPGVax
Biological/VaccineOff-the-shelf, neoantigen heat shock protein vaccine
Balstilimab
DrugBALSTILIMAB is a human monoclonal antibody that targets programmed cell death 1 (PD1)
Zalifrelimab
DrugZALIFRELIMAB is a human monoclonal immunoglobulin G1k subclass (IgG1k) antibody that specifically recognizes cytotoxic T lymphocyte-associated protein 4 (CTLA-4, also known as CD152)
Treatment groups
36 Participants
are divided into 4 treatment groupsGroup A: "Lead In": rHSC-DIPGVax MonotherapyExperimental treatment 1 intervention
Group B: Part A: rHSC-DIPGVax in Combination with BALSTILIMAB (Anti-PD1)Experimental treatment 2 interventions
Group C: Part B: Dose Escalation of ZALIFRELIMAB (Anti-CTLA4)Experimental treatment 3 interventions
Group D: Part C: Dose ExpansionExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Safety and Tolerability: Dose limiting toxicities of rHSC-DIPGVax
Number of DLT's per CTCAE version 5.0 and iRANO guidelines.
Time frame
DLT period of 28 days for rHSC-DIPGVax monotherapy2
Safety and Tolerability: Dose limiting toxicities of rHSC-DIPGVax plus BALSTILIMAB
Number of DLT's per CTCAE version 5.0 and iRANO guidelines.
Time frame
DLT period of 28 days for Part A3
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.
Time frame
DLT period of 42 days for Part BSecondary outcomes
1
Total number of DLT's for ZALIFRELIMAB at RP2D in combination with rHSC-DIPGVax and BALSTILIMAB
Number of DLT's using CTCAE version 5.0 and iRANO guidelines
Time frame
On-going during 1 year of therapy plus 3 month follow up2
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
12 month overall survival
Time frame
On-going during 1 year of therapy plus 3 month follow up3
Overall survival at 1 year
Overall survival from time of diagnostic imaging to time of death
Time frame
On-going during 1 year of therapy4
Time to progression
time to progression (from time of diagnostic imaging to time of disease progression)
Time frame
On-going during 1 year of therapy plus up to 5 years off treatmentOther outcomes
1
To evaluate biologic correlates for immune response in order to assess neo-antigen specific T cell responses
PBMC immune subsets measured via flow cytometry from peripheral blood samples
Time frame
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 up2
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
peak plasma concentration (Cmax) of BALSTILIMAB AND ZALIFRELIMAB in the blood
Time frame
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 treatment3
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
Area under the plasma concentration versus time curve (AUC) of BALSTILIMAB AND ZALIFRELIMAB in the blood
Time frame
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 treatment4
To evaluate the immunogenicity of BALSTILIMAB as mAb monotherapy with rHSC-DIPGVax and in mAb combination with ZALIFRELIMAB and rHSC-DIPGVax
Assays to assess anti drug antibody levels in the blood
Time frame
1 cycle = 42 days; Predose on 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 treatmentSponsors and contacts
Click on the lead sponsor to view all of their trials.
Ann & Robert H Lurie Children's Hospital of Chicago
Lead sponsor
Dana-Farber Cancer Institute
Collaborator
Children's Hospital of Orange County
Collaborator
University of Calgary
Collaborator
Source ClinicalTrials.gov