Personalized Immunotherapy in Adults With Upper Gastrointestinal Tract Cancers

A Phase I/II Study of Personalized Immunotherapy in Adults With Upper Gastrointestinal Tract Cancers

The purpose of this study is to determine if it is possible to make and safely administer a 'personalized' cancer vaccine for people diagnosed with an upper gastrointestinal tract cancer.

Study Overview

• Status: Withdrawn
• Conditions: Cancer of Gastrointestinal Tract
• Intervention / Treatment: Biological: personalized vaccine; Drug: Nivolumab

Detailed Description

The purpose of this study is to determine if it is possible to make and safely administer a 'personalized' cancer vaccine for people diagnosed with an upper gastrointestinal tract cancer.

It is known that cancer has mutations (changes in genetic material) that are specific to an individual person and their tumor. These mutations can cause the tumor cells to produce proteins that are different from the body's normal, healthy cells. The study will use a sample of your tumor to create a vaccine against it, with the idea being that the study vaccine will "teach" the body's immune system to recognize and attack the cancer cells. The study will examine the safety of the study vaccine when given at several time points and will examine your blood for signs that the study vaccine causes the immune system to respond.

The personalized cancer vaccine will be given alone or in combination with nivolumab. Nivolumab is a drug that blocks certain proteins on cells that help to keep immune responses in check. In a healthy person, this keeps the immune system from attacking healthy cells and tissues, but cancer cells use these proteins to keep the immune system from killing cancer cells and tumors. When these proteins are blocked, the check on the immune system is removed and immune cells may be able to recognize and kill cancer cells.

This personalized cancer vaccine is considered experimental because it is not approved by the US Food & Drug Administration (FDA) as a treatment for cancer.

The combination of nivolumab and the personalized cancer vaccine is experimental and is not FDA approved.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • University of California, San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically documented gastroespohageal or gastric adenocarcinoma.
• Measurable disease as defined by RECIST 1.1
• 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)

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.
• 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-Barré 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: anti-PD1 and personalized vaccine	Biological: personalized vaccine; Vaccine will be constructed for each subject that express multiple candidate tumor-derived neoantigens.; Drug: Nivolumab; 3mg/kg nivolumab will be administered intravenous (IV) infusion every 3 weeks for 4 doses. After 4 doses, 480 mg nivolumab will be administered intravenous (IV) infusion every 4 weeks.; Other Names: Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Quantitative frequency of TCR	1 year
Treatment-related Adverse Events	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	1 year
Progression-free survival (PFS)	1 year
Duration of response	1 year
Overall Response	1 year

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Principal Investigator: Ezra Cohen, MD, University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: November 29, 2021
• First Submitted That Met QC Criteria: November 29, 2021
• First Posted (Actual): December 10, 2021

Study Record Updates

• Last Update Posted (Actual): June 10, 2024
• Last Update Submitted That Met QC Criteria: June 7, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: immunotherapy; cancer; vaccine; nivolumab; gastrointestinal; personalized cancer vaccine; neoantigen
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: PCV-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No