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

NCT02287428 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: 14-36251986
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 2

Brief 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

Outcome Measures

Primary Outcomes (4)

• Cohorts 1, 1a, 1b, & 1c: Number of participants with Adverse Events as a measure of safety and tolerability

  To evaluate the safety and tolerability of administering NeoVax plus pembrolizumab among newly diagnosed glioblastoma patients with MGMT unmethylated tumors

  2 Years

• Cohorts 1d: Number of participants with Adverse Events as a measure of safety and tolerability

  To evaluate the safety and tolerability of administering NeoVax plus pembrolizumab and temozolomide among newly diagnosed glioblastoma patients with MGMT methylated/partially methylated tumors

  2 Years

• Cohort 1: Number of participants with at least 10 actionable peptides as a measure of study feasibility

  This information will be used to determine the feasibility of generating and administering NeoVax in participants with newly diagnosed glioblastoma.

  2 Years

• Cohort 1: Number of participants who are clinically able to initiate post-RT vaccine therapy within 12 weeks or less from date of surgery

  This information will be used to determine the feasibility of generating and administering NeoVax in participants with newly diagnosed glioblastoma.

  2 Years

Secondary Outcomes (3)

• All Cohorts: Number of participants who achieve IFN-γ T-cell response at week 16 via ELISPOT assessments

  2 Years

• Cohorts 1, 1a, 1b, & 1c: Number of participants who are alive without progression at eight months after surgery resection

  2 Years

• Cohort 1d: Number of participants who are alive without progression at 11 months after surgery resection

  2 years

Study Arms (5)

Coh 1 (Original Cohort): Standard RT Followed by NeoVax

EXPERIMENTAL

After the screening procedures confirm participant eligible to participate in the research study (must be registered to within 6 weeks of resection): * \~ 6 weeks of standard radiation therapy (RT) followed by an RT-recovery period. * During that time, participant NeoAntigen Vaccine-Preparation is created (process takes \~ 12 weeks) After participant recovers from RT and vaccine is created, participant will re-screen to confirm participant is eligible to receive study vaccinations. Once registered, participant will proceed to receive study vaccinations: \- NeoAntigen Vaccine: NeoVax will be administered on an individual basis using a dosing schedule that incorporates both priming and boost phases (\~ 7 months total: 5 priming followed by 2 boost vaccine administrations)

Radiation: Radiation Therapy; Biological: Personalized NeoAntigen Peptides; Biological: Poly-ICLC

Coh 1a: Pembrolizumab w Std RT Followed by NeoVax + Pembro

EXPERIMENTAL

* RT: Standard RT (60Gy) over 6 weeks * Pembrolizumab: Starts within 2 weeks of start of RT, and continues every 3 weeks for up to 2 years * NeoVax: Starts in the Adjuvant setting - as soon as available after RT - and is administered on days 1, 4, 8, 15, 22 \[priming doses\], 78 and 134 \[booster doses\] o NeoVax Day 1 does not have to coincide with Pembrolizumab dosing

Radiation: Radiation Therapy; Biological: Personalized NeoAntigen Peptides; Drug: Pembrolizumab; Biological: Poly-ICLC

Coh 1b: Std RT Followed by NeoVax + Pembrolizumab

EXPERIMENTAL

* RT: Standard RT (60Gy) over 6 weeks * Pembrolizumab: Starts 1-4 weeks after completion of NeoVax priming, and continues every 3 weeks for up to 2 years * NeoVax: Starts in the Adjuvant setting - as soon as available after RT - and is administered on days 1, 4, 8, 15, 22 \[priming doses\], 78 and 134 \[booster doses\] o NeoVax Day 1 does not have to coincide with Pembrolizumab dosing

Radiation: Radiation Therapy; Biological: Personalized NeoAntigen Peptides; Drug: Pembrolizumab; Biological: Poly-ICLC

Coh 1c: Std RT (+ 1 dose Pembro) Followed by NeoVax & Pembo

EXPERIMENTAL

* RT: Standard RT (60Gy) over 6 weeks * Pembrolizumab: Single dose of pembrolizumab administered within 2 weeks of start of RT; re-starts 1-4 weeks after completion of NeoVax priming, and continues every 3 weeks for up to 2 years. * NeoVax: Starts in the Adjuvant setting - as soon as available after RT - and is administered on days 1, 4, 8, 15, 22 \[priming doses\], 78 and 134 \[booster doses\] o NeoVax Day 1 does not have to coincide with Pembrolizumab dosing

Radiation: Radiation Therapy; Biological: Personalized NeoAntigen Peptides; Drug: Pembrolizumab; Biological: Poly-ICLC

Coh 1d: Std RT+TMZ Followed by 6 Cyc TMZ + NeoVax + Pembro

EXPERIMENTAL

• RT: Standard RT (60Gy) + concurrent daily temozolomide (TMZ) over 6 weeks. Concurrent TMZ @ 75 mg/m2/day for 6 weeks. Followed by: * 6 cycles of Adjuvant temozolomide (TMZ): Starts 4-6 weeks after completion of RT. TMZ (150-200 mg/m2/day) on days 1-5 of each 28-day cycle for 6 cycles. * Pembrolizumab: Starts 1-4 weeks after completion of NeoVax priming, and continues every 3 weeks for up to 2 years * NeoVax: Starts in the Adjuvant setting - as soon as available after RT - and is administered on days 1, 4, 8, 15, 22 \[priming doses\], 78 and 134 \[booster doses\] o NeoVax Day 1 does not have to coincide with Pembrolizumab dosing

Radiation: Radiation Therapy; Biological: Personalized NeoAntigen Peptides; Drug: Pembrolizumab; Drug: Temozolomide; Biological: Poly-ICLC

Interventions

Radiation Therapy RADIATION

Standard radiotherapy (approximately 60 Gy over 6 weeks)

Also known as: RT, XRT

Coh 1 (Original Cohort): Standard RT Followed by NeoVax; Coh 1a: Pembrolizumab w Std RT Followed by NeoVax + Pembro; Coh 1b: Std RT Followed by NeoVax + Pembrolizumab; Coh 1c: Std RT (+ 1 dose Pembro) Followed by NeoVax & Pembo; Coh 1d: Std RT+TMZ Followed by 6 Cyc TMZ + NeoVax + Pembro

Personalized NeoAntigen Peptides BIOLOGICAL

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.

Coh 1 (Original Cohort): Standard RT Followed by NeoVax; Coh 1a: Pembrolizumab w Std RT Followed by NeoVax + Pembro; Coh 1b: Std RT Followed by NeoVax + Pembrolizumab; Coh 1c: Std RT (+ 1 dose Pembro) Followed by NeoVax & Pembo; Coh 1d: Std RT+TMZ Followed by 6 Cyc TMZ + NeoVax + Pembro

Pembrolizumab DRUG

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).

Also known as: MK-3475, Keytruda

Coh 1a: Pembrolizumab w Std RT Followed by NeoVax + Pembro; Coh 1b: Std RT Followed by NeoVax + Pembrolizumab; Coh 1c: Std RT (+ 1 dose Pembro) Followed by NeoVax & Pembo; Coh 1d: Std RT+TMZ Followed by 6 Cyc TMZ + NeoVax + Pembro

Temozolomide DRUG

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

Also known as: Concurrent temozolomide; Concurrent TMZ

Coh 1d: Std RT+TMZ Followed by 6 Cyc TMZ + NeoVax + Pembro

Poly-ICLC BIOLOGICAL

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.

Also known as: Hiltonol

Coh 1 (Original Cohort): Standard RT Followed by NeoVax; Coh 1a: Pembrolizumab w Std RT Followed by NeoVax + Pembro; Coh 1b: Std RT Followed by NeoVax + Pembrolizumab; Coh 1c: Std RT (+ 1 dose Pembro) Followed by NeoVax & Pembo; Coh 1d: Std RT+TMZ Followed by 6 Cyc TMZ + NeoVax + Pembro

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet the following criteria on screening examination to be eligible to participate in the study (labs/tests/assessments within 14 days prior to initial study registration unless otherwise specified)
• Participant is willing and able to give written informed consent
• Pathologically confirmed WHO grade IV glioblastoma or variants (gliosarcoma, glioblastoma with oligodendroglial features, giant cell glioblastoma) with adequate tumor material for genomic sequencing. Participants will be eligible if the original diagnosis was a lower grade glioma and a subsequent histologic diagnosis of glioblastoma or its variants was made, and patient received no prior therapy other than surgery
• Patients with a diagnosis of astrocytoma with molecular features of glioblastoma will be considered eligible for trial.
• In addition, patients with IDH-mutated tumors will also continue to be eligible for trial, despite the release of updated WHO disease classifications in 2021.
• The tumor must be primarily supratentorial in location as determined by diagnostic imaging performed preoperatively
• Radiographic contrast enhancement attributable to residual tumor on post-operative imaging performed within 72 hours of resection must not exceed 1 cm in maximal diameter in biperpendicular plances (greater than 1 cm in one plane but less than 1 cm in other planes will be allowed)
• CT or MRI within 14 days prior to start of study therapy (NOTE: This criterion does not apply to Cohort 1d participants who are registering after having initiated standard of care therapy.)
• Age ≥18 years
• Karnofsky performance status ≥ 70
• Participant is a candidate for, and agrees to receive conventional external beam radiotherapy. (Patients screening for Cohort 1d can be actively receiving - or already completed - their first line conventional external beam radiotherapy.)
• No corticosteroid dosing within 5 days of radiation therapy initiation (Cohorts 1a, 1b, 1c, \& 1d).
• Normal hematologic, renal and hepatic function as defined below:
• ANC: greater or equal to 1,000 /mcl
• Platelets: greater than or equal to 100,000 /mcl

You may not qualify if:

• Participants who exhibit any of the following conditions at either screening timepoint will not be eligible for admission into or continuation on the study
• Stereotactic biopsy (without further resection);
• Tumor primarily localized in the infratentorial compartment or spinal cord - tumors with limited infratentorial compartment or spinal cord involvement are eligible;
• Radiographic or cytologic evidence of diffuse leptomeningeal extension - tumors with limited subependymal involvement are eligible;
• Participants who have received or plan to receive any additional treatment for glioblastoma aside from surgical resection and conventional radiotherapy (Cohort 1) and pembrolizumab (cohorts 1a, 1b and 1c) and temozolomide (cohort 1d), including - but not limited to - temozolomide (cohorts 1, 1a, 1b and 1c), stereotactic radiosurgery, placement of Gliadel (carmustine; BCNU) wafers, any other intratumoral or intracavitary treatment, brachytherapy, Novo-Tumor Treating Fields (Optune), or investigational therapeutic agents. (Cohort 1d participants may have already initiated or completed their RT with concomitant TMZ, and may have initiated their adjuvant TMZ at the time of study entry as long as they do not have evidence of progressive disease and have undergone a leukopheresis or blood draw with adequate mononuclear cell collection.)
• Concomitant therapy with any anti-cancer agents, other investigational anti-cancer therapies, or immunosuppressive agents including but not limited to methotrexate, chloroquine, azathioprine, etc. within six months of study participation;
• History of severe allergic reactions attributed to any vaccine therapy for the prevention of infectious diseases;
• Active, known, or suspected autoimmune disease or immunosuppressive conditions that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs) with the exception of vitiligo, type 1 diabetes, residual autoimmune-related hypothyroidism requiring hormone replacement, or psoriasis not requiring systemic treatment. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Known chronic infections with HIV, hepatitis B (HBV) or C (HCV), Hepatitis B virus DNA and testing for HCV RNA must be undetectable.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring treatment, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia;
• Any underlying medical condition, psychiatric condition or social situation that in the opinion of the investigator would compromise study administration as per protocol or compromise the assessment of AEs;
• Planned major surgery;
• Pregnant women are excluded from this study because personalized neoantigen peptides and poly-ICLC are agents with unknown risks to the developing fetus. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with personalized neoantigen peptides and poly-ICLC, nursing women are excluded from this study;
• Individuals with a history of an invasive malignancy are ineligible except for the following circumstances; a) individuals with a history of invasive malignancy are eligible if disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy; b) individuals with the following cancers are eligible if diagnosed and treated - carcinoma in situ of the breast, oral cavity or cervix and basal cell or squamous cell carcinoma of the skin;
• Hypersensitivity to pembrolizumab or any of its excipients.

Sponsors & Collaborators

• Accelerate Brain Cancer Cure: collaborator
• The Ben & Catherine Ivy Foundation: collaborator
• Merck Sharp & Dohme LLC: collaborator
• National Institutes of Health (NIH): collaborator
• Dana-Farber Cancer Institute: lead

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02113, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Radiotherapy; pembrolizumab; Temozolomide; poly ICLC

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Therapeutics; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• David A. Reardon, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: After Cohort 1 completed accrual, new patients with MGMT-unmethylated tumors are randomized to one of three new cohorts (1a, 1b, \& 1c) and new patients with MGMT-methylated tumors are registered to new cohort 1d.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prinicipal Investigator

Model Details: Patients on Cohort 1 received Neovax after completing standard RT. After Cohort 1 completed accrual, we added three new cohorts (1a, 1b, \& 1c); patients on Cohorts 1a, 1b, \& 1c (run in parallel) receive pembrolizumab (starting at different times) in addition to standard RT + NeoVax.

Study Record Dates

• First Submitted: October 29, 2014
• First Posted: November 10, 2014
• Study Start: November 1, 2014
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

US (2)