CAR T-Cell Therapy for Ovarian Cancer

Overseen By Lorna Rodriguez

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Immunosuppressants, Anticoagulants

Disqualifiers: Autoimmune disease, Active infection, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

Duration: 1 day

33 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial tests the safety, side effects, and best dose of TAG72-chimeric antigen receptor (CAR) T cells in treating patients with epithelial ovarian cancer that remains despite treatment with platinum therapy (platinum resistant). T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize TAG72, a protein on the surface of tumor cells. These TAG72-specific T cells may help the body's immune system identify and kill TAG72+ cancer cells.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor to get a clear answer based on your specific situation.

What data supports the effectiveness of the treatment CAR T-Cell Therapy for Ovarian Cancer?

Research shows that CAR T-Cell Therapy targeting TAG72 can significantly reduce tumor growth and extend survival in ovarian cancer models. This treatment has shown promise in targeting specific proteins on cancer cells, making it a potential strategy for ovarian cancer. ^{1 2 3 4 5}

Is CAR T-Cell Therapy for ovarian cancer safe?

CAR T-Cell Therapy for ovarian cancer has shown promise in research, but it can have side effects like cytokine-associated toxicities and 'on-target, off-tumor' toxicities, which means it might attack healthy tissues. These side effects are important to consider when evaluating the safety of this treatment. ^{1 3 4 6 7}

How is the TAG72-CAR T-Cell treatment different from other ovarian cancer treatments?

The TAG72-CAR T-Cell treatment is unique because it uses genetically engineered T cells to specifically target and attack ovarian cancer cells that express the TAG72 antigen, which is a protein found on the surface of these cancer cells. This approach is different from traditional treatments like chemotherapy and surgery, as it involves a personalized immunotherapy that aims to enhance the body's immune response against the cancer. ^{1 2 4 6 8}

Research Team

Lorna Rodriguez, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults over 18 with ovarian cancer that didn't respond to platinum therapy. They must have a certain level of physical fitness, no severe allergies to study drugs, and agree to use birth control. People can't join if they haven't recovered from previous treatments' side effects, have significant heart rhythm problems, active autoimmune diseases requiring steroids or other immunosuppressants, uncontrolled infections including hepatitis B/C or HIV, bleeding disorders on anticoagulants, recent strokes or brain hemorrhages.

Inclusion Criteria

My bilirubin levels are within the required range.

Your liver enzyme levels are not more than 5 times the upper limit of normal. This will be checked within 42 days before you agree to join the study.

Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable exceptions may be granted with study principal investigator (PI) approval

Exclusion Criteria

I am on medication to suppress my immune system due to an autoimmune disease.

I am currently experiencing symptoms of a blocked intestine.

I have had a gastrointestinal perforation or symptomatic diverticular disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Patients receive fludarabine and cyclophosphamide intravenously to prepare for CAR T cell infusion

3 days

3 visits (in-person)

Treatment

Patients receive TAG72-CAR T cells intraperitoneally

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Multiple visits at 1, 7, 14, 21, 28, 60, and 90 days, then 6, 9, and 12 months

Long-term follow-up

Participants are monitored for long-term safety and survival outcomes

Up to 15 years

Treatment Details

Interventions

• Cyclophosphamide
• Fludarabine
• TAG72-CAR T Cells

Trial Overview The trial tests TAG72-CAR T cells in patients with resistant epithelial ovarian cancer. Patients' own T cells are modified to target TAG72 protein on tumor cells. The safety and optimal dose of these engineered T cells will be evaluated alongside standard therapies like Fludarabine and Cyclophosphamide.

Participant Groups

Group I: Treatment (TAG72-CAR T cells) Experimental Treatment 3 Interventions

Patients receive fludarabine IV and cyclophosphamide IV on days -5 to -3. Patients receive TAG72-CAR T cells IP on day 0.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

The TAG72-BBζ CAR T cell therapy demonstrated strong effectiveness against ovarian cancer by significantly reducing tumor growth and improving survival in mouse models, indicating its potential as a treatment option.

However, challenges remain, such as reduced TAG72 expression in recurring tumors and limited T cell persistence, which could affect the long-term success of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective Targeting of TAG72+ Peritoneal Ovarian Tumors via Regional Delivery of CAR-Engineered T Cells. Murad, JP., Kozlowska, AK., Lee, HJ., et al.[2019]

Dual CAR-T cells targeting both TAG-72 and a truncated CD47 antigen show promise in improving the effectiveness of immunotherapy for ovarian cancer, potentially overcoming the limitations of single-target therapies.

The design of the truncated CD47 CAR minimizes damage to healthy tissues while enhancing the elimination of TAG-72 positive cancer cells, suggesting a safer approach for treating solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineered CAR-T cells targeting TAG-72 and CD47 in ovarian cancer. Shu, R., Evtimov, VJ., Hammett, MV., et al.[2021]

Chimeric Antigen Receptor (CAR) T cells show potential for treating epithelial ovarian cancer (EOC) due to the high presence of tumor-associated antigens (TAAs) and the unique tumor microenvironment, although robust clinical data is still lacking.

Preclinical studies suggest that CAR T cells could be effective in EOC, but further research is necessary to optimize administration methods and identify the most effective CAR types for patient treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reprogramming T-cells for adoptive immunotherapy of ovarian cancer. Genta, S., Ghisoni, E., Giannone, G., et al.[2019]

Adoptive T-cell therapies, particularly CAR T-cell therapy, are gaining attention for their potential to enhance immune responses against ovarian cancer, leveraging T cells' critical role in immune surveillance.

Recent advancements, such as dual specificity CARs and affinity-tuned single-chain Fv fragments, may improve the effectiveness and safety of CAR T-cell therapies compared to traditional T cell receptor therapies in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of chimeric antigen receptor-engineered T cells in ovarian cancer therapy. Zhang, M., Zhang, DB., Shi, H.[2021]

Adoptive transfer of genetically modified T cells, specifically those expressing chimeric antigen receptors (CARs), shows promise as a novel treatment for ovarian cancer, which is known for its poor prognosis after standard therapies.

Ovarian tumors are relatively immunogenic, meaning they can provoke a natural immune response, making them suitable candidates for T cell immunotherapy, which is currently being explored in both pre-clinical and clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive T cell immunotherapy strategies for the treatment of patients with ovarian cancer. Chekmasova, AA., Brentjens, RJ.[2022]

Chimeric antigen receptor-modified T (CAR-T) cell therapy shows promising clinical efficacy in treating ovarian cancer, as supported by various preclinical experiments and clinical trials.

While CAR-T therapy offers a novel approach to cancer treatment, it is associated with side effects and toxicities, including cytokine release syndrome and 'on-target, off-tumor' effects, which need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T cell therapy in ovarian cancer: from the bench to the bedside. Zhu, X., Cai, H., Zhao, L., et al.[2019]

In a mouse model with human Her2 expression, both high-affinity and low-affinity chimeric antigen receptor T cells (CARTs) caused liver damage, but low-affinity CARTs resulted in less toxicity and lower systemic inflammation compared to high-affinity CARTs.

Surprisingly, low-affinity CARTs showed better antitumor efficacy against Her2-positive tumors, likely due to their ability to migrate out of the liver and infiltrate tumors more effectively than high-affinity CARTs, suggesting that tuning T cell affinity can enhance safety and effectiveness in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A rational mouse model to detect on-target, off-tumor CAR T cell toxicity. Castellarin, M., Sands, C., Da, T., et al.[2021]

Genetically-modified T cells targeting the L1-CAM protein, which is over-expressed in ovarian cancer, showed promising results in laboratory tests and mouse models, indicating their potential as an immunotherapy for this deadly disease.

When administered intraperitoneally, these CE7R+ T cells significantly reduced tumor growth and ascites formation in mice, leading to improved survival rates compared to control groups, suggesting a new effective treatment strategy for advanced ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L1 Cell Adhesion Molecule-Specific Chimeric Antigen Receptor-Redirected Human T Cells Exhibit Specific and Efficient Antitumor Activity against Human Ovarian Cancer in Mice. Hong, H., Brown, CE., Ostberg, JR., et al.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Effective Targeting of TAG72+ Peritoneal Ovarian Tumors via Regional Delivery of CAR-Engineered T Cells. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Engineered CAR-T cells targeting TAG-72 and CD47 in ovarian cancer. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Reprogramming T-cells for adoptive immunotherapy of ovarian cancer. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Application of chimeric antigen receptor-engineered T cells in ovarian cancer therapy. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Adoptive T cell immunotherapy strategies for the treatment of patients with ovarian cancer. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

CAR-T cell therapy in ovarian cancer: from the bench to the bedside. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

A rational mouse model to detect on-target, off-tumor CAR T cell toxicity. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

L1 Cell Adhesion Molecule-Specific Chimeric Antigen Receptor-Redirected Human T Cells Exhibit Specific and Efficient Antitumor Activity against Human Ovarian Cancer in Mice. [2020]