Dose Escalation and Expansion Study of TROP2 CAR Engineered IL-15- Transduced Cord Blood-derived NK Cells in Combination With Cetuximab in Patient With Colorectal Cancer (CRC) With Minimal Residual Disease (MRD)

NCT06358430 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2023-1017NCI-2024-03107
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

To find the highest and/or recommended dose of TROP2-CAR-NK cells combined with cetuximab in participants with MRD CRC.

Conditions

Colorectal Cancer; Minimal Residual Disease

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs)

  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)

Dose Escalation + Dose Expansion

EXPERIMENTAL

Up to 5 dose levels of TROP2-CAR-NK cells will be tested in the Dose Escalation phase. Up to 12 participants maximum will be enrolled at any dose level, in groups of 3 participants at a time. 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 recommended dose of TROP2-CAR-NK cells is found. When that dose level is confirmed, the final group of 12 participants will be enrolled at that dose level.

Drug: Fludarabine Phosphate; Drug: Cyclophosphamide; Drug: Cetuximab; Drug: TROP2-CAR-NK Cells; Drug: Rimiducid (AP1903); Procedure: Lymphodepleting Chemotherapy

Interventions

Fludarabine Phosphate DRUG

Given by IV

Also known as: Fludarabine, Fludara®

Dose Escalation + Dose Expansion

Cyclophosphamide DRUG

Given by IV

Also known as: Cytoxan®, Neosar®

Dose Escalation + Dose Expansion

Cetuximab DRUG

Given by IV

Also known as: C225, Erbitux™, IMC-C225, MOAB C225

Dose Escalation + Dose Expansion

TROP2-CAR-NK Cells DRUG

Given by IV

Dose Escalation + Dose Expansion

Rimiducid (AP1903) DRUG

Given by IV

Dose Escalation + Dose Expansion

Lymphodepleting Chemotherapy PROCEDURE

Given by Chemotherapy

Dose Escalation + Dose Expansion

Eligibility Criteria

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

You may qualify if:

• Participants must be 18 years or older.
• Participants must be willing and able to provide informed consent.
• Willing and able to comply with clinical trial instructions and requirements. Individuals lacking the ability, based on reasonable medical judgment, to understand and appreciate the nature and consequences of participation in this study will not be eligible for participation.
• In both the dose escalation and dose expansion cohorts, participants must have documented colorectal cancer (CRC) with MRD following complete disease resection followed by standard-of-care adjuvant treatment. MRD is defined as NO evidence of radiological disease (including patients with undefinable lesion with max diameter \<1 cm or with a short axis \< 1cm for lymph nodes) and presence of circulating ctDNA in the bloodstream.
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 3).
• Life expectancy \> 3 months.
• A female patient is eligible to participate if at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 OR
• A WOCBP who agrees to follow the contraceptive guidelines in Appendix 4 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 4 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 \[â-hCG\]) pregnancy test will be required.
• Participants must have adequate organ function as defined below (Table 1) within 10 days prior to the start of lymphodepleting chemotherapy:
• Table 1. Adequate Organ Function Laboratory Values Systemic Function Test Laboratory Value Hematologic ANC = ≥1500/ƒÊL Platelets = ≥100,000/ƒÊL Hemoglobin = ≥9.0 g/dLa Renal CrCl by Cockcroft-Gault formula = ≥45 mL/min for patients with creatinine \>1.5 x ULNb Hepatic Total bilirubin = ≤1.5 x ULN OR direct bilirubin ≤ULN for patients with total bilirubin levels \>1.5 x ULN AST and ALT = ≤2.5 x ULN (≤5 x ULN for patients with history of resected liver metastases) Coagulation PT/INR aPT = ≤1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range
• Left ventricular ejection fraction \>50%. Of note, those patients with risk factors and/or with LVEF \<55% additional testing may need to be performed as per institutional guidelines and/or PI guidance.

You may not qualify if:

• Participants with known active disease by RECIST v1.1.
• 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 3 half-lives, whichever is shorter, prior to the start of lymphodepleting chemotherapy. For patients 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). If a participants 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 or colitis.
• 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. Guerin, 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., FluMistR) are live attenuated vaccines and are not allowed.
• Prior 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.
• 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.
• Known history of active tuberculosis (Mycobacterium Tuberculosis).

Sponsors & Collaborators

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

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm, Residual

Interventions

fludarabine phosphate; fludarabine; Cyclophosphamide; Cetuximab; AP 1903 reagent

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Maria Pia Morelli, MD, PhD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria Pia Morelli, MD, PhD

CONTACT

(713) 792-2828; GIClinicalTrials@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: April 5, 2024
• First Posted: April 10, 2024
• Study Start: December 2, 2024
• Primary Completion (Estimated): January 18, 2029
• Study Completion (Estimated): January 18, 2029
• Last Updated: January 15, 2026

Record last verified: 2026-01

Locations

US (1)