Modified CAR T Cells for Ovarian Cancer

Recruiting at 1 trial location

Overseen By Amy R. Lankford, PhD

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Precigen, Inc

Must not be taking: Immunosuppressants, Investigational agents

Disqualifiers: Cardiac conditions, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

71 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase I/Ib dose escalation, dose expansion, study to evaluate the safety and identify the recommended dose of modified immune cells PRGN-3005 (autologous chimeric antigen receptor (CAR) T cells developed by Precigen, Inc.) in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has spread to other places in the body, that has come back and is resistant to platinum chemotherapy. Autologous CAR T cells are modified immune cells that have been engineered in the laboratory to specifically target a protein found on tumor cells and kill them.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you must be at least 28 days post systemic steroids and 14 days from previous cytotoxic chemotherapy before cell collection.

What data supports the effectiveness of the treatment PRGN-3005 UltraCAR-T cells for ovarian cancer?

Research shows that CAR T-cell therapy, which is similar to PRGN-3005 UltraCAR-T cells, has shown promise in treating ovarian cancer by enhancing the body's immune response to target and kill cancer cells. Studies have demonstrated that CAR T-cells can effectively reduce tumor growth and improve survival in ovarian cancer models. ^{1 2 3 4 5}

Is CAR T-cell therapy safe for ovarian cancer treatment?

CAR T-cell therapy for ovarian cancer has shown promise, but it can have side effects like cytokine-associated toxicities (immune system overreaction) and 'on-target, off-tumor' toxicities (attacking healthy tissues). Studies suggest that intraperitoneal (IP) administration of CAR-T cells may be safer than intravenous (IV) administration, as it circulates less in non-tumor tissues. ^{1 2 3 6 7}

What makes the PRGN-3005 UltraCAR-T treatment unique for ovarian cancer?

PRGN-3005 UltraCAR-T treatment is unique because it uses modified T cells that are engineered to specifically target and attack ovarian cancer cells, offering a personalized approach that differs from traditional chemotherapy or surgery. This therapy leverages the body's immune system to fight cancer, potentially providing a more targeted and effective treatment option. ^{1 2 5 6 8}

Research Team

Amy R. Lankford, PhD

Principal Investigator

Precigen, Inc

Eligibility Criteria

This trial is for women with advanced, recurrent ovarian, fallopian tube, or primary peritoneal cancer that's resistant to platinum chemotherapy. Participants must have measurable disease and be in good health otherwise. They should not be pregnant and agree to use two contraception methods during the study.

Inclusion Criteria

My blood tests show my organs are working well.

I have a BRCA mutation and have finished all standard treatments, including PARP inhibitors.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I have or have had treatment for brain metastases.

Patients within 28 days of receiving another investigational agent

I haven't had cancer, except for certain skin cancers or cervical changes, in the last 5 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive autologous PRGN-3005 UltraCAR-T cells via IP or IV administration with or without lymphodepleting chemotherapy

4 weeks

Multiple visits for dose escalation and administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular visits for monitoring adverse events and T cell presence

Long-term follow-up

Participants are monitored for evidence of anti-tumor activity

5 years

Treatment Details

Interventions

• PRGN-3005 UltraCAR-T cells

Trial Overview The trial tests PRGN-3005 UltraCAR-T cells, which are modified immune cells designed to target and kill tumor cells in patients with certain types of cancer that have spread or returned after treatment.

Participant Groups

Group I: Treatment (PRGN-3005 UltraCAR-T cells) IV Administration Experimental Treatment 1 Intervention

Patients receive autologous PRGN-3005 UltraCAR-T cells via IV administration with or without lymphodepleting chemotherapy.

Group II: Treatment (PRGN-3005 UltraCAR-T cells) IP Administration Experimental Treatment 1 Intervention

Patients receive autologous PRGN-3005 UltraCAR-T cells via IP administration with or without lymphodepleting chemotherapy.

Who Is Running the Clinical Trial?

Precigen, Inc

Lead Sponsor

Trials

7

Recruited

300+

PGEN Therapeutics, Inc., a subsidiary of Precigen, Inc.

Lead Sponsor

Trials

3

Recruited

200+

Findings from Research

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]

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]

NK-CAR-iPSC-NK cells, engineered with a specific CAR construct, show enhanced anti-tumor activity against ovarian cancer compared to traditional T-CAR-expressing NK cells and non-CAR NK cells, indicating their potential as a more effective immunotherapy.

In an ovarian cancer model, NK-CAR-iPSC-NK cells not only inhibited tumor growth and improved survival rates but also exhibited similar in vivo activity to T-CAR T cells while demonstrating lower toxicity, making them a promising 'off-the-shelf' option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human iPSC-Derived Natural Killer Cells Engineered with Chimeric Antigen Receptors Enhance Anti-tumor Activity. Li, Y., Hermanson, DL., Moriarity, BS., et al.[2019]

Adoptive cell therapy (ACT) represents a promising immunotherapy for epithelial ovarian cancer (EOC), utilizing personalized lymphocyte manipulation to enhance cancer rejection, with various strategies including tumor-infiltrating lymphocytes and CAR-T cells.

Recent advancements in genomics and immuno-engineering have improved the effectiveness of ACT, particularly through neoantigen-based strategies and dendritic cell-based immunotherapies, showing modest but encouraging results in EOC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell therapies in ovarian cancer. Sarivalasis, A., Morotti, M., Mulvey, A., et al.[2021]

Engineered CAR T cells targeting both Muc16 and WT1 antigens in ovarian cancer show enhanced anticancer activity, especially against tumors with low Muc16 expression, indicating a promising approach to overcome treatment resistance.

The use of a bispecific T cell engager (BiTE) allows these CAR T cells to recruit additional T cells to attack cancer cells, enhancing the overall effectiveness of the therapy in both laboratory and mouse models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual targeting ovarian cancer by Muc16 CAR T cells secreting a bispecific T cell engager antibody for an intracellular tumor antigen WT1. Mun, SS., Meyerberg, J., Peraro, L., et al.[2023]

Engineered CAR T cells targeting both Muc16 and WT1 antigens in ovarian cancer show enhanced anticancer activity, especially against tumors with low Muc16 expression, indicating a promising approach to improve treatment efficacy.

The use of a bispecific T cell engager (BiTE) allows these CAR T cells to recruit additional T cells to attack cancer cells, demonstrating a novel strategy to overcome the limitations of traditional CAR T cell therapies in heterogeneous tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual targeting ovarian cancer by Muc16 CAR-T cells secreting a bispecific T cell engager antibody for an intracellular tumor antigen WT1. Mun, SS., Peraro, L., Meyerberg, J., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

Human iPSC-Derived Natural Killer Cells Engineered with Chimeric Antigen Receptors Enhance Anti-tumor Activity. [2019]

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

Cell therapies in ovarian cancer. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Dual targeting ovarian cancer by Muc16 CAR T cells secreting a bispecific T cell engager antibody for an intracellular tumor antigen WT1. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Comparing Intraperitoneal and Intravenous Personalized ErbB2CAR-T for the Treatment of Epithelial Ovarian Cancer. [2022]

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

A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. [2023]

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

Dual targeting ovarian cancer by Muc16 CAR-T cells secreting a bispecific T cell engager antibody for an intracellular tumor antigen WT1. [2023]