NCT02287428

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

A Phase I Study of a Personalized NeoAntigen Cancer Vaccine With Radiotherapy Plus Pembrolizumab/MK-3475 Among Newly Diagnosed Glioblastoma Patients

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 56 (estimated)
• Sponsor: Dana-Farber Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

It is known that glioblastomas have mutations 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 glioblastoma to recur. Methylguanine methyltransferase (MGMT) is a DNA repair protein which can be increased in some cancers, including glioblastoma. MGMT works to repair the DNA of cancer cells that are damaged by treatment. If a tumor is found to be "unmethylated", it means there is more MGMT present in the tumor than one that is "methylated". Methylation of MGMT is believed to make tumor cells more responsive to drugs like temozolomide. Studies have shown that temozolomide provides a very small improvement in outcome for many patients whose glioblastoma is MGMT-unmethylated. Patients with glioblastoma usually receive six weeks of radiation with a daily chemotherapy called temozolomide after their surgery, followed by six to twelve months of additional temozolomide. In this study, only participants whose tumors are MGMT-methylated will receive temozolomide; those participants whose tumors are MGMT-unmethylated will not receive temozolomide, as studies have shown that temozolomide provides a very small improvement in outcome for many patients whose glioblastoma is MGMT-unmethylated. On this trial, an initial cohort of participants (Cohort 1) will receive the Personalized NeoAntigen Vaccine (5 priming doses and 2 booster doses over \~ 20 weeks) after having completed six weeks of standard radiation. The study will examine the safety of the vaccine when given at several different time points and will examine the participant blood cells for signs that the vaccine induced an immune response. 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 cohorts 1a, 1b and 1c 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

Type	Name	Description
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.

Timeline

• Start date: 2014-11-01
• Primary completion: 2027-02-01
• Completion: 2028-02-01
• First posted: 2014-11-10
• Last updated: 2026-04-17

Locations

2 sites across 1 country: United States