Modified CAR T Cells for Ovarian Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using modified immune cells called PRGN-3005 UltraCAR-T cells, a type of cell therapy. These engineered cells target and destroy ovarian, fallopian tube, or primary peritoneal cancer cells that have spread and resisted standard platinum chemotherapy. The trial will assess the safety of this treatment and determine the optimal dose, with patients receiving the treatment either directly into the abdomen or through an IV. Women with advanced cancer that hasn't responded to typical treatments and have noticeable tumors may be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that PRGN-3005 UltraCAR-T cells are likely to be safe for humans?

Research has shown that PRGN-3005 UltraCAR-T cells, used to treat certain cancers, are generally safe. In studies, patients tolerated these modified immune cells well. Importantly, no deaths or severe side effects, such as nerve damage, occurred. The treatment did not cause side effects severe enough to halt dose escalation. Additionally, any immune system reactions remained mild, not exceeding a moderate level.

Both methods of administering the treatment—directly into the abdomen or through a vein—yielded similar safety results. Patients generally fared well regardless of the administration method. These findings suggest that PRGN-3005 UltraCAR-T cells are generally safe, making them a promising option for further cancer research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ovarian cancer?

Researchers are excited about PRGN-3005 UltraCAR-T cells for ovarian cancer because they represent a cutting-edge approach using modified CAR T cells. Unlike traditional treatments like chemotherapy and surgery, PRGN-3005 specifically targets cancer cells by engineering a patient's own immune cells to recognize and attack them. This treatment is administered either directly into the abdomen (IP) or through an IV, offering flexible delivery options. By harnessing the body's immune system, PRGN-3005 UltraCAR-T cells have the potential to provide a more personalized and effective treatment with potentially fewer side effects than conventional therapies.

What evidence suggests that PRGN-3005 UltraCAR-T cells might be an effective treatment for ovarian cancer?

Research has shown that PRGN-3005 UltraCAR-T cells hold promise in shrinking tumors in patients with ovarian, fallopian tube, or primary peritoneal cancer. In this trial, participants will receive PRGN-3005 UltraCAR-T cells either via IP or IV administration, with or without lymphodepleting chemotherapy. Studies found that 67% of patients experienced tumor reduction after just one IV infusion of these specially modified immune cells, administered with a treatment that temporarily lowers immune cell numbers to enhance the new cells' effectiveness. One patient who received a second infusion after 12 months saw their main tumor shrink by 28%. The treatment appears well-tolerated, with no major side effects reported at certain doses. These early results suggest that PRGN-3005 could be an effective option for patients with these hard-to-treat cancers. ^{1 2 3 5 6}

Who Is on the Research Team?

Amy R. Lankford, PhD

Principal Investigator

Precigen, Inc

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. investors.precigen.com investors.precigen.com/news-releases/news-release-details/precigen-announces-positive-phase-1-data-prgn-3005-autologous

Precigen Announces Positive Phase 1 Data for PRGN ... PRGN-3005 resulted in a decrease in tumor burden in 67% of patients who received just one IV infusion following lymphodepletion. We are ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.5590

Phase 1/1b study of PRGN-3005 autologous UltraCAR-T ... Results: PRGN-3005 was well tolerated at up to 65.5 x 105 cells/kg. There have been no deaths, dose-limiting toxicities, neurotoxicity, grade ≥3 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03907527

Study Details | NCT03907527 | Modified Immune Cells ... 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 ...

4. cancernetwork.com cancernetwork.com/view/early-prgn-3005-data-may-reignite-car-t-cell-research-for-ovarian-cancer

Early PRGN-3005 Data May Reignite CAR T-cell Research ... PRGN-3005 autologous UltraCAR-T cells appear well-tolerated and decreases tumor burden in a population of patients with advanced ...

5. investors.precigen.com investors.precigen.com/news-releases/news-release-details/preclinical-data-prgn-3005-ultracar-tr-demonstrate-superior

Preclinical Data for PRGN-3005 UltraCAR-T® Demonstrate ... Specifically, a single administration of PRGN-3005 showed significantly superior expansion and preferred memory phenotype of UltraCAR-T in vivo ...

6. prnewswire.com prnewswire.com/news-releases/precigen-announces-positive-phase-1-data-for-prgn-3005-autologous-ultracar-t-cells-manufactured-overnight-for-infusion-next-day-to-advanced-stage-platinum-resistant-ovarian-cancer-patients-301842691.html

Precigen Announces Positive Phase 1 Data for PRGN ... PRGN-3005 was well-tolerated with no dose limiting toxicities, no CRS greater than Grade 2, and no neurotoxicity – – PRGN-3005 cells ...