Study of TROP2 CAR Engineered IL15-transduced Cord Blood-derived NK Cells Delivered Intraperitoneally for the Management of Platinum Resistant Ovarian Cancer, Mesonephric-like Adenocarcinoma, and Pancreatic Cancer

NCT05922930 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2022-0687NCI-2023-05027
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

To find the recommended dose of TROP2- CAR-NK given intraperitoneally (directly into the abdominal cavity) to patients with highgrade serous ovarian cancer that has not responded to previous treatment or is resistant to treatment.

Conditions

Pancreatic Cancer; Ovarian Cancer; Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  through study completion; an average of 1 year

Study Arms (1)

TROP2-CAR-NK

EXPERIMENTAL

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.

Drug: TROP2-CAR-NK; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

TROP2-CAR-NK DRUG

Given by IP (intraperitoneal)

TROP2-CAR-NK

Cyclophosphamide DRUG

Given by IV (vein)

TROP2-CAR-NK

Fludarabine DRUG

Given by IV (vein)

TROP2-CAR-NK

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be 18 years or older.
• Subjects must be willing and able to provide informed consent.
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• A female participant is eligible to participate if at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 1
• A WOCBP who agrees to follow the contraceptive guidelines in Appendix 1 during the treatment period and for at least 3 months after the last dose of study treatment.
• Subjects must have measurable disease present as defined by modified RECIST v1.1 criterion, and have disease present in the peritoneal cavity or retroperitoneal lymph nodes. Disease outside the peritoneal cavity is allowed as long as metastases are present within the peritoneal cavity or retroperitoneum.
• Subject tumors must demonstrate at least 1+ TROP2 expression by immunohistochemistry.
• Subjects must be at least 3 weeks from last cytotoxic chemotherapy at the time of starting lymphodepleting chemotherapy.
• Subjects must be willing to undergo intraperitoneal port placement and scheduled peritoneal fluid and peripheral blood draws.
• Subjects must have adequate organ function as defined in the following table (Table 1). Specimens must be collected within 10 days prior to the start of study treatment.
• Table 1. Adequate Organ Function Laboratory Values Systemic Function Test Laboratory Value Hematologic Absolute neutrophil count (ANC) ≥1500/µL Platelets ≥100,000/µL Hemoglobin ≥8.0 g/dL (transfusion is allowed)a Renal Creatinine OR Creatinine clearance (CrCl) by Cockroft-Gault
• x ULNb
• mL/min for participants with creatinine \> 1.5 x ULNb Hepatic Total bilirubin ≤1.5 x ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 x ULN AST (SGOT) and ALT (SGPT) ≤2.5 x ULN (≤5 x ULN for participants with liver metastases) Coagulation International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 x ULN unless participate is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants ALT (SGPT) = alanine aminotransferase (serum glutamic pyruvic transaminase);AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.
• Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks of the screening test. Participants may be on a stable dose of erythropoietin (≥ approximately 3 months).

You may not qualify if:

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• Pregnant, breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 3 months after the last dose of trial treatment.
• If a WOCBP has a positive urine pregnancy test within 72 hours prior to hospital admission that cannot be confirmed as negative, a serum pregnancy test will be required (see Appendix 1).
• Has received systemic anti-cancer therapy including investigational agents within 4 weeks of starting lymphodepleting chemotherapy.
• Participants must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline.
• Participants with ≤ Grade 2 neuropathy, alopecia, or other non-relevant AEs may be deemed eligible at the discretion of the PI. If a participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine.
• Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; However, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• Is currently receiving another investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in-situ cancers.
• Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
• History of interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Pancreatic Neoplasms; Ovarian Neoplasms; Adenocarcinoma

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Amir Jazaeri, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amir Jazaeri, MD

CONTACT

(713) 745-1613; aajazaeri@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2023
• First Posted: June 28, 2023
• Study Start: October 11, 2023
• Primary Completion (Estimated): October 15, 2027
• Study Completion (Estimated): January 15, 2028
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (1)