Phase 1b Study Of TRICK-NK In Combination With T-Dxd In Treatment-Refractory Breast Cancers

NCT07553390 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2026-0140NCI-2026-03278
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of TGFBR-2 KO CD70 CAR NK (TRICK-NK) in combination with 2 doses of T-Dxd that can be given to participants who have advanced breast cancer. The safety of TRICK-NK will also be studied. The goal of Part 1 (dose escalation) of this clinical research study is to find the highest tolerable dose of TRICK-NK (in combination with T-Dxd) that can be given to participants who have advanced breast cancer. The goal of Part 2 (dose expansion) of this clinical research study is to learn if the dose of TRICK-NK found in Part 1 can help to control the disease. The optional schedule optimization phase will test a shorter interval between the NK cell infusion and the first dose of T-Dxd.

Conditions

Breast Cancer

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 (2)

Dose Escalation Phase: Treatment with TRICK-NK + T-Dxd (21 Days Interval)

EXPERIMENTAL

This phase will be conducted with a maximum of 21 participants to examine three escalating cell dose levels and one de-escalating cell dose level (level -1) with T-Dxd (21 days +/-3 days interval between cell infusion and each dose of T-Dxd treatment), to determine the safety and select the RP2D.

Drug: TGFBR2 KO iC9/TROP2.CAR/IL-15 NK cells; Drug: Trastuzumab deruxtecan (T-DXd); Drug: Rimiducid

Dose Expansion Phase Cohort A and B: Treatment with TRICK-NK + T-Dxd (21 Days Interval)

EXPERIMENTAL

Investigators will enroll two cohorts of participants with up to 15 participants within each cohort to the RP2D to further evaluate the safety and preliminary efficacy.

Drug: TGFBR2 KO iC9/TROP2.CAR/IL-15 NK cells; Drug: Trastuzumab deruxtecan (T-DXd); Drug: Rimiducid

Interventions

TGFBR2 KO iC9/TROP2.CAR/IL-15 NK cells DRUG

Given by IV

Dose Escalation Phase: Treatment with TRICK-NK + T-Dxd (21 Days Interval); Dose Expansion Phase Cohort A and B: Treatment with TRICK-NK + T-Dxd (21 Days Interval)

Trastuzumab deruxtecan (T-DXd) DRUG

Given by IV

Also known as: Enhertu

Dose Escalation Phase: Treatment with TRICK-NK + T-Dxd (21 Days Interval); Dose Expansion Phase Cohort A and B: Treatment with TRICK-NK + T-Dxd (21 Days Interval)

Rimiducid DRUG

Given by IV

Also known as: AP1903

Dose Escalation Phase: Treatment with TRICK-NK + T-Dxd (21 Days Interval); Dose Expansion Phase Cohort A and B: Treatment with TRICK-NK + T-Dxd (21 Days Interval)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed breast cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for nonnodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam.
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of TRICK-NK cells in patients \<18 years of age, children are excluded from this study.
• For patients with triple negative subtype (TNBC, ER\<1%, PR 1%, HER2 negative per ASCO/ CAP 2018 guideline), must have received at least one dose of Sacituzumab govitecan or anti-TROP2 antibody drug conjugate (ADC)
• Patients must be at least 2 weeks from last cytotoxic chemotherapy, tyrosine kinase inhibitors or other targeted therapies at the time of administration of lymphodepleting chemotherapy.
• Patients must be at least 3 months from any cell therapy for malignancy (this is not a criteria for repeated treatments).
• Localized radiotherapy to 1 or more disease sites is allowed prior to the lymphodepleting chemotherapy, if there are additional measurable non-irradiated disease sites.
• Eastern Cooperative Oncology Group performance status 0 or 1 (Performance level as measured by Karnofsky for patients \> 16 years of age, see Appendix A).
• Adequate organ function at screening, as defined by the following:
• Renal: Estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration equation) ≥50 ml/min/1.73 m2
• Hepatic: alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 x upper limit of normal (ULN) or ≤ 5 x ULN if documented liver metastases, total bilirubin ≤ 1.5 mg/dL or ≤ 3.0 mg/dL for patients with Gilbert's Syndrome. No history of liver cirrhosis.
• Cardiac: Cardiac ejection fraction ≥ 50%, no clinically significant pericardial effusion as determined by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan, and no symptomatic cardiac disease or history of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication) Pulmonary: No clinically significant pleural effusion (per principal investigator \[PI\] judgement), and baseline oxygen saturation ≥ 92% on room air. Subjects with active interstitial lung disease (ILD)/pneumonitis requiring treatment with systemic steroids will be excluded.
• Hematological: absolute neutrophil count (ANC) ≥ 1000/mm3, platelet count ≥ 75,000/mm3, and hemoglobin ≥ 8 g/dL. Coagulation: International normalized ratio (INR) ≤ 1.5 ULN and activated partial thromboplastin time (aPTT) ≤ 1.5 ULN. Patients on therapeutic doses of anticoagulation medication must have INR and/or aPTT ≤ the upper limit of the therapeutic range for intended use.
• Able to provide written informed consent.
• Weight ≥40 kg (due to safety of NK-cell).

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry:
• Presence of clinically significant ongoing Grade ≥ 2 toxicity unequivocally associated with the previous anticancer treatment, as determined by the PI. Toxicities related to prior surgery, radiation, prior systemic immune checkpoint inhibitors and chemotherapy should be resolved to Grade 1 or below prior to lymphodepletion.
• Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials for management or not responding to appropriate therapy. Note: Patients with simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
• Known active hepatitis B or C.
• Known human immunodeficiency virus (HIV).
• Presence of active neurological disorder(s).
• Active autoimmune disease within 12 months of enrollment (excluding low-grade psoriasis or well-controlled autoimmune thyroid disease).
• Amyloidosis or POEMS syndrome.
• Symptomatic or uncontrolled central nervous system involvement or signs of cord compression. In the case radiation therapy is indicated, the washout must be at least 14 days.
• Patients must not have any other malignancies within the past 2 years except for in situ carcinoma of any site, adequately treated (without recurrence post resection or post radiotherapy) carcinoma of the cervix or basal or squamous cell carcinomas of the skin, or active non-life-threatening second malignancy that would not, in the investigator's opinion, potentially interfere with the patient's ability to participate and/or complete this trial. Examples include but are not limited to urothelial cancer Grade Ta or T1 and adenocarcinoma of the prostate treated by active surveillance.
• Presence of any other serious medical condition that may endanger the patient at investigator's discretion, including but not limited to:
• New York Heart Association Class III or IV heart failure
• Myocardial infarction or stroke ≤ 26 weeks prior to CAR NK cell infusion
• Unstable angina within ≤ 13 weeks prior to CAR NK cell infusion unless the underlying disease has been corrected by procedural intervention (e.g., stent, bypass)
• Severe aortic stenosis

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

UT MD Anderson

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

trastuzumab deruxtecan; AP 1903 reagent

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Bora Lim, MD

  UT MD Anderson

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bora Lim, MD

CONTACT

(713) 745-0689; blim@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: April 23, 2026
• First Posted: April 28, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): March 30, 2036
• Study Completion (Estimated): March 30, 2038
• Last Updated: April 28, 2026

Record last verified: 2026-04

Locations

US (1)