Personalized NeoAntigen Cancer Vaccine w RT Plus Pembrolizumab for Patients With Newly Diagnosed GBM

Summary

This research study is studying a new type of vaccine as a possible treatment for patients with glioblastoma. This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the intervention to use for further studies. "Investigational" means that the intervention is being studied and that research doctors are trying to find more about it. It also means that the FDA (U.S. Food and Drug Administration) has not approved the Personalized NeoAntigen Cancer Vaccine for any use in patients, including people with glioblastoma.

The purpose of the initial study cohort (Cohort 1) is to determine if it is possible to make and administer safely a vaccine against glioblastoma by using information gained from specific characteristics of the participants tumor. It is known that glioblastomas have mutations (changes in genetic material) that are specific to an individual patient's tumor. These mutations can cause the tumor cells to produce proteins that appear very different from the body's own cells. It is possible that these proteins used in a vaccine may induce strong immune responses, which may help the body fight any tumor cells that could cause the glioblastoma to come back in the future.

Three additional cohorts (1a, 1b, \& 1c) were added to the study following completion of accrual to the original study cohort (cohort 1). Each new cohort receives NeoVax and radiation therapy as administered to cohort 1 and will also receive pembrolizumab: cohort 1a patients will start pembrolizumab w/in 2 weeks after start of RT, and continue every 3 weeks for up to 2 years; cohort 1b patients will start pembrolizumab 2-4 weeks after completion of NeoVax priming, and continue every 3 weeks for up to 2 years; cohort 1c patients will receive a single dose of pembrolizumab administered within 2 weeks after start of RT, re-start 2-4 weeks after completion of NeoVax priming, and continue every 3 weeks for up to 2 years. The rationale for adding these new cohorts is: 1) to assess the safety and feasibility of NeoVax when administered with pembrolizumab; and 2) to determine if the timing of anti-PD-1 administration impacts the immunogenicity of NeoVax.

An additional sub-study cohort (1d) is being added for patients whose tumor is MGMT-methylated. Cohort 1d will enroll patients with tumors for which the MGMT status is methylated or partially methylated; patients on cohort 1d will receive standard daily temozolomide during radiation and as adjuvant therapy for up to six cycles following completion of radiation therapy. The rationale for adding cohort 1d is to determine the safety and feasibility of NeoVax when administered with pembrolizumab and temozolomide.

Conditions

• Glioblastoma

Interventions

RADIATION

Radiation Therapy

Standard radiotherapy (approximately 60 Gy over 6 weeks)

BIOLOGICAL

Personalized NeoAntigen Peptides

NeoVax Vaccine (Personalized NeoAntigen Peptides + Poly-ICLC) will be administered on an individual basis using a dosing schedule that incorporates both priming and boost phases.

DRUG

Pembrolizumab

Pembrolizumab will be administered every 3 weeks at a flat dose of 200 mg intravenously. Pembrolizumab should be administered as a 30 minute IV infusion (Pembrolizumab treatment cycle intervals may be increased due to toxicity per protocol).

DRUG

Temozolomide

Concurrent Temozolomide (TMZ) = 75 mg/m2/day for 6 weeks, administered with XRT

DRUG

Temozolomide

Adjuvant Temozolomide (TMZ) = 150 mg/m2/day on days 1-5 of each 28-day cycle for up to 6 adjuvant cycles

BIOLOGICAL

Poly-ICLC

NeoVax Vaccine (Personalized NeoAntigen Peptides + Poly-ICLC) will be administered on an individual basis using a dosing schedule that incorporates both priming and boost phases.

Sponsors & Collaborators

• The Ben & Catherine Ivy Foundation

  collaborator OTHER

• Accelerate Brain Cancer Cure

  collaborator OTHER

• Merck Sharp & Dohme LLC

  collaborator INDUSTRY

• National Institutes of Health (NIH)

  collaborator NIH

• Dana-Farber Cancer Institute

  lead OTHER

Principal Investigators

• David A. Reardon, MD · Dana-Farber Cancer Institute

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-11-30

Primary Completion

2027-02-28

Completion

2028-02-29

Countries

• United States

Study Locations