Personalized Immunotherapy in Adults With Advanced Cancers Immunotherapy in Adults With Advanced Cancers

Sponsor
Ezra Cohen (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03568058
Collaborator
(none)
30
1
4
60.2
0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if it is possible to make and administer safely a 'personalized' vaccine to treat patients that have been diagnosed with advanced cancer and are not candidates for curative therapy.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

The purpose of this study is to determine if it is possible to make and administer safely a 'personalized' vaccine to treat patients that have been diagnosed with advanced cancer and are not candidates for curative therapy.

This 'personalized' vaccine will use information gained from specific characteristics of your own cancer. It is known that cancer has mutations (changes in genetic material) that are specific to an individual and 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 (protective) responses, which may help your body fight any tumor cells that could cause your cancer to come back in the future. The study will examine the safety of the vaccine when given at several time points and will examine your blood cells for signs that the vaccine induced an immune response.

The personalized vaccine will be given in combination with an anti-PD1 antibody, pembrolizumab, which is used with the intention to increase anti-cancer immunity (protection). Pembrolizumab is a type of drug that blocks certain proteins made by some types of immune system cells, such as T cells, and some cancer cells. These proteins help keep immune responses in check and can keep T cells from killing cancer cells. When these proteins are blocked, the "brakes" on the immune system are released and T cells are able to kill cancer cells better.

This personalized vaccine is considered experimental because this is not an FDA approved therapy for cancer.

Pembrolizumab is FDA approved for the treatment of melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), classical Hodgkin lymphoma (cHL), urothelial carcinoma, microsatellite instability-high cancer (MSI-H), gastric cancer, cervical cancer, and hepatocellular carcinoma (HCC). Pembrolizumab is considered experimental (investigational) for the treatment of all other cancer types.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b Safety and Feasibility Study of Personalized Immunotherapy in Adults With Advanced Cancers
Actual Study Start Date :
Jul 26, 2018
Anticipated Primary Completion Date :
Aug 1, 2022
Anticipated Study Completion Date :
Aug 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: vaccine and anti-PD-1

personalized vaccine and anti-PD-1 administered concurrently at the start of study therapy

Drug: personalized vaccine
Vaccine will be constructed for each subject that express multiple candidate tumor-derived neoantigens.

Drug: Pembrolizumab
200 mg pembrolizumab will be administered intravenous (IV) infusion every 3 weeks.
Other Names:
  • keytruda
  • Experimental: anti-PD1 before vaccine

    anti-PD-1 antibody for 6 weeks followed by personalized vaccine therapy

    Drug: personalized vaccine
    Vaccine will be constructed for each subject that express multiple candidate tumor-derived neoantigens.

    Drug: Pembrolizumab
    200 mg pembrolizumab will be administered intravenous (IV) infusion every 3 weeks.
    Other Names:
  • keytruda
  • Experimental: anti-PD1 and vaccine

    anti-PD-1 antibody followed by personalized vaccine therapy

    Drug: personalized vaccine
    Vaccine will be constructed for each subject that express multiple candidate tumor-derived neoantigens.

    Drug: Pembrolizumab
    200 mg pembrolizumab will be administered intravenous (IV) infusion every 3 weeks.
    Other Names:
  • keytruda
  • Experimental: vaccine

    personalized vaccine therapy

    Drug: personalized vaccine
    Vaccine will be constructed for each subject that express multiple candidate tumor-derived neoantigens.

    Outcome Measures

    Primary Outcome Measures

    1. Quantitative frequency of TCR [1 year]

    2. Number of Participants with Treatment-related Adverse Events [1 year]

    Secondary Outcome Measures

    1. Overall Response [1 year]

      RECIST 1.1

    2. Progression-free survival (PFS) [1 year]

      Duration of time from start of study treatment until objective tumor progression or death.

    3. Time to Progression [1 year]

      Duration of time from start of study treatment until objective tumor progression.

    4. Overall Survival [1 year]

      Duration of time from start of study treatment to death

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria

    • Histologically or cytologically documented incurable solid tumor [excluding lymphoma].

    • Measurable disease as defined by RECIST 1.1

    • Progressed on or be intolerant to therapies that are known to provide clinical benefit.

    • Non-measurable disease by RECIST 1.1 and high-risk (>50% over 5 years) of mortality

    • At least one tumor site accessible for biopsy.

    • Adequate organ function

    • Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy.

    Exclusion Criteria

    • Currently receiving or has received another anti-cancer therapy within 4 weeks prior to first dose of vaccine study treatment.

    • Currently receiving or has received PD1/PDL1 inhibitor immunotherapy within 4 weeks prior to first dose of study treatment.

    • Currently receiving or has received anti-PD1 or anti-CTLA4 treatment during the vaccine preparation period.

    • Receiving TNF pathway inhibitors, PI3 kinase inhibitors, systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of study medication.

    • Received an investigational agent within 28 days prior to the first dose of study drug.

    • Untreated brain metastases; individuals with treated and stable metastases are eligible. Eligible subjects should have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for brain metastases for at least 4 weeks and are neurologically stable for 8 weeks (confirmed by MRI) prior to administration of experimental therapy

    • Has known history of Human Immunodeficiency Virus (HIV).

    • Received a diagnosis of hepatitis B or hepatitis C for which there is no clear evidence of natural immunity, immunity subsequent to vaccination, or successful eradication of the virus following antiviral therapy (individuals who are hepatitis C antibody positive may be enrolled if negative viral load confirmed).

    • History of autoimmune disease including: inflammatory bowel disease (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis (e.g. Wegener's granulomatosis); central nervous system or motor neuropathy considered of autoimmune origin (e.g. Guillain-BarrĂ© syndrome, myasthenia gravis, multiple sclerosis). Individuals with vitiligo, Sjogren's Syndrome, interstitial cystitis, Graves' or Hashimoto's Disease, celiac disease, DM1, or hypothyroidism stable on hormone replacement will be allowed with Study Medical Monitor's approval.

    • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.

    • History of receiving a solid organ transplant or allogeneic bone marrow transplant.

    • Major surgical procedure within 28 days prior to the first dose of study drug.

    • If female, pregnant or breastfeeding.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UCSD Medical Center San Diego California United States 92103

    Sponsors and Collaborators

    • Ezra Cohen

    Investigators

    • Principal Investigator: Erza Cohen, MD, University of California, San Diego

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Ezra Cohen, Professor of Medicine, University of California, San Diego
    ClinicalTrials.gov Identifier:
    NCT03568058
    Other Study ID Numbers:
    • 180410
    First Posted:
    Jun 26, 2018
    Last Update Posted:
    Feb 4, 2022
    Last Verified:
    Feb 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Ezra Cohen, Professor of Medicine, University of California, San Diego
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 4, 2022