Neoplasms

All Conditions

Rare Diseases

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Vaccines

Temozolomide

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

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)

* 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

* 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

* 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

• 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

Standard radiotherapy (approximately 60 Gy over 6 weeks)

Radiation Therapy

NeoVax will be administered on an individual basis using a dosing schedule that incorporates both priming and boost phases.

Personalized NeoAntigen Vaccine

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).

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

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

David A Reardon, MD

Jennifer Stefanik, NP

Justin Jordan, MD

David Reardon, MD

David A. Reardon, MD

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.

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.

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.

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.

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

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

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

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

This information will be used to assess the induction of neoantigen-specific cellular immune responses following administration of Neovax with or without pembrolizumab.

Estimate of the proportion of participants alive without disease progression at eight months after resection.

Estimate of the proportion of participants alive without disease progression at eleven months after resection.

The Ben & Catherine Ivy Foundation

Accelerate Brain Cancer Cure

Merck Sharp & Dohme LLC

National Institutes of Health (NIH)

Dana-Farber Cancer Institute

Prinicipal Investigator

Digestive System Diseases

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Poly ICLC

Patients will receive radical resection surgery and at least one circle of post-operative chemotherapy. After chemotherapy, personalized neoantigen vaccines will be administered subcutaneously.

Patients will have complete resection of primary tumor without preoperative chemotherapy. Patients will receive postoperative chemotherapy and subsequently personalized vaccines on days 1, 4, 8, 15, 22 (priming phase) and weeks 12, 20 (boosting phase). Personalized vaccines will consist of several distinct peptides (the dose is 0.3 mg/peptide) that are grouped into 2-4 pools and 0.5 mg of poly-ICLC as the adjuvant for each pool. Injection sites will be 2-4 separate sites of the subject's thighs.

Personalized neoantigen vaccine

Shiwei Guo, Doctor

Suizhi Gao, Master

Gang Jin, Doctor

This clinical trial is to evaluate the safety and impact on prognosis of personalized neoantigen peptide-based vaccines, which are based on next-generation sequencing and major histocompatibility complex affinity prediction algorithm, in patients with pancreatic ductal adenocarcinoma. The hypothesis of this study is that personalized neoantigen vaccines will be safe and can systemically elicit measurable neoantigen-specific immunologic responses in patients. Participants will receive complete macroscopic resection of primary tumor, standard adjuvant chemotherapy and subsequently personalized neoantigen vaccines.

This is a single-center, open-label Phase Ib clinical trial. In this trial, adult subjects with pancreatic ductal adenocarcinoma who have completed resection of the primary tumor and who have not undergone preoperative chemotherapy will be enrolled in the study. Eligible enrolled patients all will undergo tumor resection and all receive adjuvant chemotherapy prior to preparation of the personalized neoantigen vaccine. After the chemotherapy finish, subsequently patients will receive a priming immunization with five doses of the personalized neoantigen vaccine over one month and a boosting immunization with two doses three months later. This clinical trial will examine the safety and effect of the personalized neoantigen vaccine when given at several different time points and will examine the participant's peripheral blood cells for signs that the vaccine induces immunologic responses. Finally we will establish the typical flow to assess efficiency and safety of vaccines according to the different reactivity of patients, as a result, to explore the most suitable practical approaches for applying personalized pancreatic tumor vaccines.

Clinical Trial on Personalized Neoantigen Vaccine for Pancreatic Tumor

Clinical Trial to Evaluate Safety and Effect of Personalized Neoantigen Vaccine for Pancreatic Tumor Following Surgical Resection and Adjuvant Chemotherapy

Ex vivo Enzyme-linked Immunospot assay will be performed to detect the levels of interferon-γ responses of the neoantigen peptides in the stimulation of peripheral blood mononuclear cells. Data will be presented as the ratio of the adjusted spot-forming count of peptide stimulation to the corresponding non-stimulated negative control.

The percentages of immune cells including natural killer (NK) cells, T cells, B cells, macrophages, monocytes, dendritic cells and granulocytes as well as their subtypes will be detected in the peripheral blood of patients during the vaccination. The percentages of specific T-cell or B-cell clonotypes will also be detected during the vaccination. Ten-color flow cytometry and single-cell transcriptome sequencing will be performed to evaluate the percentage of the immune cell populations. Single-cell T/B-cell repertoire sequencings will be performed to profile the expansion of T-cell or B-cell clonotypes.

Safety will be assessed by the rate of grade 3 or worse adverse events (graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0).

The time between resection surgery and the tumor recurrence (radiological assessment of disease status according to RECIST1.1 criteria).

The time between resection surgery and the death (any cause).

The rate of patients without the abnormal elevation of the serum CA19-9 (Cancer Antigen 19-9) or CA72-4 (Cancer Antigen 72-4) levels will be assessed during the vaccination and post-treatment follow-up.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Personalized NeoAntigen Cancer Vaccine w RT Plus Pembrolizumab for Patients With Newly Diagnosed GBM	NCT02287428	Glioblastoma	Radiation Thera... Personalized Ne... Pembrolizumab Temozolomide Temozolomide	18 Years -	Dana-Farber Cancer Institute
Clinical Trial on Personalized Neoantigen Vaccine for Pancreatic Tumor	NCT03558945	Pancreatic Tumo...	Personalized ne...	20 Years - 75 Years	Anda Biopharmaceutical Development (Shenzhen) Co., Ltd.

Spots Global Cancer Trial Database for personalized neoantigen vaccine