TROP2-CAR-NK Cells for Platinum-Resistant Ovarian Cancer

Overseen By Amir Jazaeri, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anticancer, Immunosuppressants, Steroids, others

Disqualifiers: Pregnancy, Autoimmune, CNS metastases, others

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

Compensation: Varies

Number of Visits: 20

Duration: 1 day

51 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment for high-grade serous ovarian cancer that has resisted previous treatments, using engineered cells called TROP2-CAR-NK cells, a type of immunotherapy. The main aim is to determine a safe dose when these cells are administered directly into the abdominal area. Participants will receive one dose of the treatment and undergo several check-ups, including blood draws and CT scans. This trial may suit women with ovarian cancer who have not responded to at least two rounds of chemotherapy, especially if the cancer remains in the abdominal area. 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.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you must be at least 3 weeks from your last cytotoxic chemotherapy and 4 weeks from any systemic anti-cancer therapy before starting the trial treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that TROP2-CAR-NK cells might help treat ovarian cancer. These natural killer (NK) cells can shrink tumors in ovarian cancer models, indicating promising effectiveness.

Regarding safety, earlier studies tested TROP2-CAR-NK cells in people to determine a safe dose. Researchers continue to closely monitor treatments in this trial phase for safety, and patients have generally tolerated them well. So far, reports of severe side effects have not emerged, but research and monitoring continue.

Overall, while this treatment remains experimental, early results are encouraging for both safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about TROP2-CAR-NK cells for platinum-resistant ovarian cancer because this treatment harnesses the power of the immune system in a novel way. Unlike standard treatments like chemotherapy, which attack cancer cells directly, TROP2-CAR-NK cells are engineered to specifically target and destroy cancer cells by recognizing the TROP2 protein commonly found on these cells. This method not only offers a more precise attack on cancer but also minimizes damage to healthy cells, potentially reducing side effects. Moreover, the use of Natural Killer (NK) cells could lead to a more robust and sustained immune response against the cancer, offering hope for patients with limited options.

What evidence suggests that TROP2-CAR-NK is effective for platinum-resistant ovarian cancer?

Research has shown that natural killer (NK) cells, like those used in the TROP2-CAR-NK treatment, can effectively reduce tumor size in ovarian cancer models. In this trial, participants will receive TROP2-CAR-NK cells, designed to target TROP2, a protein often found on the surface of ovarian cancer cells. Early findings suggest that TROP2-CAR-NK cells may attack these cancer cells more effectively. Engineering NK cells with TROP2-CAR aims to enhance the body's immune response against the cancer. Although researchers are still studying this approach, initial data is promising for those with ovarian cancer unresponsive to standard treatments. ^{1 2 3 4 6}

Who Is on the Research Team?

Amir A. Jazaeri

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with certain types of cancer (high-grade serous ovarian, mesonephric-like adenocarcinoma, or pancreatic) that are resistant to standard treatments. Participants must have an ECOG performance status of 0 or 1, agree to contraception if applicable, and have adequate organ function. They should not be pregnant/breastfeeding and must have failed previous chemotherapy lines.

Inclusion Criteria

My cancer can be measured and is present in my abdomen or lymph nodes near my spine.

My cancer, originating from the female reproductive tract or peritoneal lining, has been confirmed as mesonephric-like adenocarcinoma by MD Anderson Cancer Center.

I have had platinum-based chemotherapy before and it did not work.

Exclusion Criteria

My tumor is affecting a major blood vessel or has cavities inside it.

I have not had any cancer treatment or experimental drugs in the last 4 weeks.

I haven't needed systemic treatment for an autoimmune disease in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine for 3 days

1 week

3 visits (in-person)

Treatment

Participants receive 1 dose of TROP2-CAR-NK cells delivered intraperitoneally

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness, including objective response rates at week 12

12 weeks

Up to 16 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Fludarabine
• TROP2-CAR-NK

Trial Overview The study tests TROP2-CAR-NK cells delivered into the abdomen combined with Cyclophosphamide and Fludarabine in patients with specific cancers. It aims to find the optimal dose for those whose cancer hasn't responded well to other treatments.

How Is the Trial Designed?

Group I: TROP2-CAR-NK Experimental Treatment 3 Interventions

Participants will receive 1 dose of TROP2-CAR-NK and will visit the study clinic up to 16 times to have tests and procedures (such as blood draws, biopsies, and CT scans). Participants will receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine) for 3 days in a row. Participants will receive cyclophosphamide and fludarabine by vein over about 3 hours total.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

This phase I safety trial involves 12 patients with recurrent ovarian cancer, aiming to evaluate the safety and toxicity of intraperitoneal infusions of natural killer (NK) cells derived from umbilical cord blood, with or without prior immunosuppressive treatment.

The study will assess whether these NK cells can safely expand and remain active in the body, potentially offering a new therapeutic strategy for patients with a poor prognosis, especially if no severe toxicity is observed in the initial cohorts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal infusion of ex vivo-cultured allogeneic NK cells in recurrent ovarian carcinoma patients (a phase I study). Hoogstad-van Evert, J., Bekkers, R., Ottevanger, N., et al.[2022]

Natural killer (NK) cells, whether derived from induced pluripotent stem cells (iPSCs) or activated peripheral blood (PB), significantly reduced tumor burden in a mouse model of ovarian cancer, demonstrating their potential as effective immunotherapy.

Mice treated with three doses of iPSC-derived or expanded PB-NK cells showed improved median survival (98 and 97 days, respectively) compared to untreated mice (73 days), indicating that iPSC-derived NK cells are as effective as PB-NK cells for treating ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induced Pluripotent Stem Cell-Derived Natural Killer Cells for Treatment of Ovarian Cancer. Hermanson, DL., Bendzick, L., Pribyl, L., et al.[2021]

Engineered cord blood-derived natural killer (NK) cells, modified with CAR-CD19 and IL-15, showed effective targeting and killing of leukemia cells in laboratory tests and improved survival in a mouse model of lymphoma.

This approach not only enhances the efficacy of NK cells in treating cancers but also includes a safety mechanism (the iC9 suicide gene) to eliminate the cells if necessary, reducing the risk of adverse effects like graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity. Liu, E., Tong, Y., Dotti, G., et al.[2021]

In newly diagnosed high-grade serous carcinoma (HGSC), specific subpopulations of decidual-like natural killer (dl-NK) cells were identified that correlate with tumor characteristics, indicating a potential immune evasion mechanism.

The study found that HGSC tumor cells can suppress the activity of NK cells through a process called trogocytosis, where NK cells acquire CD9 from tumor cells, leading to reduced anti-tumor responses; targeting CD9 may enhance NK cell effectiveness in immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-grade serous ovarian tumor cells modulate NK cell function to create an immune-tolerant microenvironment. Gonzalez, VD., Huang, YW., Delgado-Gonzalez, A., et al.[2023]

Cytokine-induced killer lymphocytes (CIK) generated from patients with epithelial ovarian cancer (EOC) showed strong antitumor activity against platinum-resistant ovarian cancer cells in both laboratory tests and animal models, indicating their potential as a new treatment option.

The study demonstrated that CIK could effectively target and kill patient-derived ovarian cancer cells, even those that survived previous treatment with carboplatin, suggesting a promising avenue for immunotherapy in challenging cases of EOC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical immunotherapy with Cytokine-Induced Killer lymphocytes against epithelial ovarian cancer. Capellero, S., Erriquez, J., Melano, C., et al.[2021]

A novel dual-effect cord blood natural killer cell (CBNKC) was developed that co-expresses high-affinity PD-1 (HAPD1) and a chimeric antigen receptor (CAR) targeting CD19, showing enhanced anti-tumor effects compared to standard CAR19 CBNKCs.

In both in vitro and in vivo tests, the HAPD1 CAR CBNKCs demonstrated significantly stronger cytotoxicity against CD19-positive tumor cells, indicating their potential as an effective immunotherapy strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Construction and evaluation of dual-effect cord blood natural killer cells expressing highaffinity PD-1 and chimeric antigen CD19 receptor]. Zhong, H., Zou, Q., Liu, H., et al.[2023]

Intraperitoneal (IP) delivery of interleukin-2 activated natural killer (NK) cells in a mouse model of ovarian cancer resulted in effective tumor clearance and stable engraftment, with NK cells persisting for up to 54 days post-injection.

The study demonstrated that NK cells maintained their ability to kill ovarian cancer cells after IP infusion, suggesting that this delivery method could enhance the therapeutic potential of NK cell treatments in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal delivery of human natural killer cells for treatment of ovarian cancer in a mouse xenograft model. Geller, MA., Knorr, DA., Hermanson, DA., et al.[2021]

A novel CAR targeting CD44 was developed and shown to effectively kill CD44-positive ovarian cancer cells, demonstrating strong potential for treating ovarian cancer stem cells that contribute to recurrence.

The engineered NK-92 cells with the CD44 CAR maintained their effectiveness even in the presence of cisplatin, and combining CD44NK treatment with cisplatin resulted in greater anti-tumor activity than using them sequentially.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NK Cell-Mediated Eradication of Ovarian Cancer Cells with a Novel Chimeric Antigen Receptor Directed against CD44. Klapdor, R., Wang, S., Morgan, MA., et al.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS5626

Phase I/II study of TROP2 CAR engineered IL15 ... This is a phase I/II study of the intraperitoneal delivery of TROP2-CAR/IL-15 transduced cord blood (CB)-NK cells for recurrent/progressive ovarian cancer, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05922930

NCT05922930 | Study of TROP2 CAR Engineered IL15- ... Primary Objectives: 1. To determine the safety and optimal cell dose of TROP2-CAR/IL15-transduced CB-NK cells[TROP2-CAR NK cells (KSR)]delivered ...

3. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/anti-trop2-car-il-15-transduced-cord-blood-derived-natural-killer-cells

Clinical Trials Using Anti-TROP2-CAR-IL-15-transduced ... Review the clinical trials studying anti-trop2-car-il-15-transduced cord blood-derived natural killer cells on this list and use the filters to refine the ...

4. withpower.com withpower.com/trial/phase-2-adenocarcinoma-11-2023-8e593

TROP2-CAR-NK Cells for Platinum-Resistant Ovarian ... Research shows that natural killer (NK) cells, like those used in the TROP2-CAR-NK treatment, can effectively reduce tumor burden in ovarian cancer models.

5. reporter.nih.gov reporter.nih.gov/search/14E9CE024F8FC5D27598B8961CAA4A01A2FFCEB861BF/project-details/11159405

Next-Generation Engineered NK Cell Immunotherapy for ... We hypothesize that targeting TROP2 with iC9/TROP2CAR/IL-15 NK cells will greatly improve outcomes for platinum-resistant ovarian cancer and that by targeting ...

6. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2022-0687.html

Phase I/II study of TROP2 CAR engineered IL15- ... Phase I/II study of TROP2 CAR engineered IL15-transduced cord blood-derived NK cells delivered intraperitoneally for the management of platinum resistant ...