Phase 1 Dose Escalation and Expansion Study of TROP2 CAR Engineered IL15-transduced Cord Blood-derived NK Cells in Patients With Advanced Solid Tumors (TROPIKANA)

NCT06066424 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2023-0161NCI-2023-08351
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

To find the recommended dose of TROP2- CAR-NK cells that can be given to participants with advanced forms of solid tumors.

Conditions

Solid Tumors

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 (3)

Dose Escalation

EXPERIMENTAL

Participants who are enrolled in Dose Escalation, Participants will be assigned to a dose level of TROP2- CAR-NK cells based on when you join this study. Up to 5 dose levels of TROP2-CARNK cells will be tested. At least 3 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of TROP2-CAR-NK cells is found. Participants who are enrolled in the Dose Expansion, Participants will receive TROP2-CAR-NK cells at the recommended dose that was found in the Dose Escalation.

Drug: Rimiducid; Drug: TROP2-CAR-NK Cells; Drug: Fludarabine phosphate; Drug: Cyclophosphamide

Dose Expansion Cohort 1

EXPERIMENTAL

Participants who are enrolled in Dose Escalation, Participants will be assigned to a dose level of TROP2- CAR-NK cells based on when you join this study. Up to 5 dose levels of TROP2-CARNK cells will be tested. At least 3 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of TROP2-CAR-NK cells is found. Participants who are enrolled in the Dose Expansion, Participants will receive TROP2-CAR-NK cells at the recommended dose that was found in the Dose Escalation.

Drug: Rimiducid; Drug: TROP2-CAR-NK Cells; Drug: Fludarabine phosphate; Drug: Cyclophosphamide

Dose Expansion Cohort 2

EXPERIMENTAL

Participants who are enrolled in Dose Escalation, Participants will be assigned to a dose level of TROP2- CAR-NK cells based on when you join this study. Up to 5 dose levels of TROP2-CARNK cells will be tested. At least 3 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of TROP2-CAR-NK cells is found. Participants who are enrolled in the Dose Expansion, Participants will receive TROP2-CAR-NK cells at the recommended dose that was found in the Dose Escalation.

Drug: Rimiducid; Drug: TROP2-CAR-NK Cells; Drug: Fludarabine phosphate; Drug: Cyclophosphamide

Interventions

Rimiducid DRUG

Given by (IV) vein

Dose Escalation; Dose Expansion Cohort 1; Dose Expansion Cohort 2

TROP2-CAR-NK Cells DRUG

Given by (IV) vein

Dose Escalation; Dose Expansion Cohort 1; Dose Expansion Cohort 2

Fludarabine phosphate DRUG

Given by (IV) vein

Also known as: Fludarabine, Fludara®

Dose Escalation; Dose Expansion Cohort 1; Dose Expansion Cohort 2

Cyclophosphamide DRUG

Given by (IV) vein

Also known as: Cytoxan®, Neosar®

Dose Escalation; Dose Expansion Cohort 1; Dose Expansion Cohort 2

Eligibility Criteria

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

You may qualify if:

• Patients must meet the following criteria for study entry:
• Participants must be 18 years or older.
• Participants must be willing and able to provide informed consent.
• In the dose escalation, participants must have histologically documented locally advanced, unresectable, or metastatic solid tumor that has relapsed or progressed following local standard treatments that are known to prolong survival, or for which no standard treatment is available, or refused such therapy.
• In dose expansion Cohort 1, patients must have histologically documented locally advanced, unresectable, or metastatic NSCLC. Participants should have received at least two prior lines of therapy in the advanced setting. Participants with metastatic PD-L1-positive disease will be expected to have prior immunotherapy unless contraindicated. Participants with actionable alterations (e.g., EGFR, ALK, BRAF V600E, RET, ROS1, MET, NTRK) should have received prior FDA-approved targeted therapy.
• In dose expansion Cohort 2, patients must have histology documented locally advanced or metastatic HER2-negative/HER2-low breast cancer (IHC 0, IHC 1, or IHC 2+/ in situ hybridization negative) breast cancer. Participants should have received at least one prior line of therapy in the advanced setting. Participants with metastatic TNBC that is PD-L1 positive will be expected to have prior immunotherapy unless contraindicated. Participants with HR-positive disease will be expected to have received a prior cyclin- dependent kinase 4/6 inhibitor in the metastatic or adjuvant setting.
• Participant tumors must demonstrate TROP2 expression of 2+ or 3+ as determined by IHC test at the MDACC Clinical Laboratory Improvements (CLIA) Laboratories (Clinical Lab or Clinical Translational Unit; Appendix 8).
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 3).
• Life expectancy ≥3 months.
• 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 2 OR
• A WOCBP who agrees to follow the contraceptive guidelines in Appendix 2 during the study treatment period and for 6 months post TROP2-CAR-NK cell infusion.
• Female participants who become pregnant or suspect pregnancy must immediately notify their doctor. Females participants who become pregnant will be taken off study.
• Male participants must agree to follow the contraceptive guidelines in Appendix 2 during the study treatment period and for 6 months post TROP2-CAR-NK cell infusion. Male participants who father a child or suspect that they have fathered a child must immediately notify their doctor.
• WOCBP must have a negative urine pregnancy test within 72 hours prior to the start of lymphodepleting chemotherapy. If a WOCBP has a urine pregnancy test that cannot be confirmed as negative, a serum (beta-human chorionic gonadotropin \[β-hCG\]) pregnancy test will be required.

You may not qualify if:

• Participants who meet any of the following criteria will not be eligible:
• Pregnant, breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 6 months post TROP2-CAR-NK cell infusion.
• Has received systemic anticancer therapy within 2 weeks or 5 half-lives, whichever is shorter, prior to the start of lymphodepleting chemotherapy. For participants treated with monoclonal antibodies, at least 3 weeks must have elapsed prior to the start of lymphodepleting chemotherapy. Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 3 weeks after the last dose of the previous investigational agent.
• 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 principal investigator (PI)/co-PIs. If a participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to the start of lymphodepleting chemotherapy.
• Has received prior radiotherapy within 2 weeks of the start of lymphodepleting chemotherapy. 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-CNS disease.
• Has received a live vaccine within 6 weeks prior to TROP2-CAR-NK infusion and for at least 24 months post infusion. 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, and typhoid vaccine. Seasonal influenza and COVID- 19 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.
• Prior CAR T or NK cell or other genetically modified T or NK cell therapy.
• Has diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent).
• 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 patients 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. Patients with previously treated brain metastases may participate if they completed radiation therapy, are clinically stable, and without requirement of steroid treatment for at least 2 weeks prior to study enrollment.
• 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 (ILD) that required steroids or has current pneumonitis/ILD.
• Active infection requiring systemic therapy.
• Known human immunodeficiency virus (HIV) infection.
• Known active or chronic hepatitis B or hepatitis C virus infection.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bellicum Pharmaceuticals: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Interventions

fludarabine phosphate; fludarabine; Cyclophosphamide

Intervention Hierarchy (Ancestors)

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

Study Officials

• Ecaterina Dumbrava, M D

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ecaterina Dumbrava, M D

CONTACT

(713) 792-3934; eeileana@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: September 27, 2023
• First Posted: October 4, 2023
• Study Start: October 24, 2023
• Primary Completion (Estimated): April 30, 2038
• Study Completion (Estimated): April 30, 2040
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

US (1)