What side effects are associated with this type of intervention?

Common treatments for BRCA gene mutations include platinum-based chemotherapy, PARP inhibitors, and immunotherapy. Platinum-based chemotherapy, such as cisplatin plus gemcitabine, can cause hematologic toxicities like neutropenia, thrombocytopenia, and anemia, as well as nonhematologic toxicities. PARP inhibitors, like olaparib, are associated with side effects such as nausea, fatigue, anemia, and potential hematologic toxicities. Immunotherapy, including immune checkpoint inhibitors, may lead to side effects like fatigue, skin reactions, and immune-related adverse events such as pneumonitis and colitis.

What prior FDA approvals exist?

The FDA has approved several treatments for BRCA gene mutations that involve immune system activation. Notably, PARP inhibitors such as olaparib, rucaparib, and niraparib have been approved for BRCA-mutated cancers, including ovarian and prostate cancers. These drugs work by exploiting the DNA repair weaknesses in BRCA-mutated cells, leading to cancer cell death. Additionally, immune checkpoint inhibitors like pembrolizumab have shown efficacy in tumors with high tumor mutational burden, which can include BRCA-mutated cancers. These treatments aim to enhance the body's immune response to target and destroy cancer cells.

What other types of research exist?

Promising alternatives for BRCA gene mutation patients include: 1) PARP inhibitors (e.g., olaparib, niraparib) which target DNA repair mechanisms specific to BRCA mutations, 2) Immune checkpoint inhibitors (e.g., pembrolizumab, nivolumab) which enhance the immune response against tumors, and 3) Combination therapies involving immune checkpoint inhibitors and other agents (e.g., nivolumab plus relatlimab) to improve efficacy in resistant cases.

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Cancer Vaccine

Cancer Vaccine for BRCA Gene Mutation

Phase 1

Recruiting

Led By Susan Domchek, MD

Research Sponsored by University of Pennsylvania

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Normal bone marrow, hepatic, and renal function

Minimum of 2 clear sites on the skin to allow for injection

Must not have

Cardiac pre-excitation syndromes

Previous treatment with INO-5401 or IL-12 containing therapy, or any other DNA immunotherapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up for 2 years after last dose of study treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new vaccine to prevent cancer in people with BRCA1 or BRCA2 mutations. The vaccine aims to boost the immune system to help it fight off cancer cells. It is currently being evaluated for its effectiveness.

Who is the study for?

This trial is for adults over 18 with BRCA1 or BRCA2 mutations who've had breast, ovarian, pancreatic (excluding neuroendocrine), or prostate cancer but are now free of disease. Participants must have completed adjuvant therapy and be post-menopausal if female. They should not have significant heart issues, bleeding disorders, active infections like HIV or hepatitis B/C, recent major surgery, or require steroids/immunosuppressants.

What is being tested?

The study tests an experimental vaccine called INO-5401 to prevent cancer in individuals with BRCA gene mutations. It examines the vaccine's safety and immune system activation using a new delivery method involving Cellectra 2000 alongside another agent named INO-9012.

What are the potential side effects?

Potential side effects may include reactions at the injection site such as pain and swelling, flu-like symptoms including fever and fatigue, muscle aches, possible impacts on blood cells leading to increased infection risk. The full extent of side effects will be studied.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My liver, kidneys, and bone marrow are functioning normally.

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I have at least 2 clear areas on my skin suitable for injections.

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I carry a BRCA1 or BRCA2 mutation.

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I am fully active and can carry on all my pre-disease activities without restriction.

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I am a woman and have gone through menopause.

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I have had breast, ovarian, pancreatic (not neuroendocrine), or prostate cancer and completed treatment with no signs of the disease.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a condition that causes early heartbeats.

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I have not had treatments with INO-5401, IL-12, or DNA immunotherapy.

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I have not had major surgery in the last 4 weeks.

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I am not currently using, nor plan to use, steroids or immunosuppressants.

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I have a history of a serious illness or condition that weakens my immune system.

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I have hepatitis B or C with ongoing viral activity.

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I have not received any blood products in the last 2 weeks.

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I am HIV positive.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ for 2 years after last dose of study treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~for 2 years after last dose of study treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and for 2 years after last dose of study treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose Limiting Toxicities

Secondary study objectives

Antigen-specific immune response

Side effects data

From 2021 Phase 1 & 2 trial • 56 Patients • NCT03606213

100%

Injection site reaction

Bipolar depression with hypomania

100%

80%

60%

40%

20%

Study treatment Arm

Cohort B - Arm 1

Cohort A - Arm 1

Cohort A - Arm 2

Cohort A - Arm 3

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: INO-5401 and INO-9012Experimental Treatment3 Interventions

Participants receive INO-5401 and INO-09012 vaccine, followed by electroporation, on Day 1, Week 4, Week 8, and Week 12

Group II: INO-5401Experimental Treatment2 Interventions

Participants receive INO-5401 vaccine, followed by electroporation, on Day 1, Week 4, Week 8, and Week 12

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cellectra 2000

2019

Completed Phase 1

~50

INO-9012

2014

Completed Phase 2

~150

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for BRCA gene mutations include PARP inhibitors and immune-based therapies. PARP inhibitors work by blocking the PARP enzyme, which helps repair DNA damage in cells. In BRCA-mutated cells, which already have compromised DNA repair mechanisms, this leads to cell death. Immune-based therapies, such as experimental cancer vaccines, aim to activate the immune system to recognize and attack cancer cells. This is particularly important for BRCA mutation patients because their cells are more prone to developing cancer due to defective DNA repair. By enhancing the immune response, these therapies can potentially provide a more targeted and effective treatment option.

Combinatorial therapy of immune checkpoint and cancer pathways provides a novel perspective on ovarian cancer treatment.Neoadjuvant treatment of locally advanced esophageal and junctional cancer: the evidence-base, current key questions and clinical trials.Ovarian cancer BRCA1 gene therapy: Phase I and II trial differences in immune response and vector stability.