Phase 1 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)
To find the highest and/or recommended dose of TROP2-CAR-NK cells combined with cetuximab in participants with MRD CRC.
• 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.
⁃ Adequate respiratory reserve defined as dyspnea Grade 0 or 1 and saturated oxygen \>92% in room air.
⁃ Willing to undergo mandatory blood collections and biopsies as required by the study.
⁃ Willing to stay within a 2-hour drive (approximately 100-mile radius) of the study site during the first 4 weeks after the TROP2-NK cell infusion.