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About
To find the recommended dose of TROP2- CAR-NK cells that can be given to participants with advanced forms of solid tumors.
Full description
Primary Objective:
Secondary Objectives:
To determine the antitumor activity of TROP2-CAR-NK cells in participants with high TROP2-expressing NSCLC and high TROP2-expressing HER2-negative/low breast
cancer. Although the clinical benefit of TROP2-CAR-NK cells has not yet been established, the intent of offering this treatment is to provide a possible therapeutic benefit and thus, the participant will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability.
To quantify the persistence of infused allogeneic donor TROP2-CAR-NK cells in the peripheral blood of the recipient.
To evaluate tissue and blood-based biomarkers associated with response and resistance to TROP2-CAR-NK cell infusion.
Exploratory Objectives:
Enrollment
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Volunteers
Inclusion and exclusion criteria
Inclusion Criteria:
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:
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.
Participants must have measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Appendix 3).
Participants must have adequate organ function as defined below 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/µL Platelets ≥100,000/µL Hemoglobin ≥9.0 g/dLa Renal Creatinine OR CrCl by Cockcroft-Gault formula ≤1.5 × ULNb
≥45 mL/min for patients with creatinine >1.5 × ULNb Hepatic Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels >1.5 × ULN AST and ALT ≤2.5 × ULN (≤5 × ULN for patients with liver metastases) Coagulation PT/INR aPTT ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
ALT=alanine aminotransferase; ANC=absolute neutrophil count; aPTT=activated partial thromboplastin time; AST=aspartate aminotransferase; CrCl=creatinine clearance; INR=international normalized ratio; PT=prothrombin time; ULN=upper limit of normal.
Left ventricular ejection fraction >50%.
Adequate respiratory reserve defined as dyspnea Grade 0 or 1 and saturated oxygen >92% in room air.
Prior treatment with TROP2-targeted therapy will be allowed.
Willing to undergo mandatory blood collections and biopsies as required by the study.
Willing to sign consent for long-term follow-up on protocol PA17-0483.
Willing to stay within a 2-hour drive (approximately 100-mile radius) of the study site during the first 2 weeks after the TROP2-NK cell infusion.
Exclusion Criteria
Participants who meet any of the following criteria will not be eligible:
Primary purpose
Allocation
Interventional model
Masking
54 participants in 3 patient groups
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Central trial contact
Ecaterina Dumbrava, M D
Data sourced from clinicaltrials.gov
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