Phase I/Ib Study of NK Expressing an Affinity-enhanced T-cell Receptor (TCR) Against the NY-ESO-1
M.D. Anderson Cancer Center · MD Anderson Cancer Center, Houston, Texas
The goal of this clinical research study is to find a recommended dose of donated NK cells that can be given along with chemotherapy to patients with advanced cancers. The safety and effects of this therapy will also be studied.
Eligibility: 16 Years to 80 Years · All · 1. Patients with all cancer histology, with an HLA-A\*02:01, HLA-A\*02:05 or HLA-A\*02:06 positive and a positive expression of NY-ESO-1 (\>/= 50% tumor cells 2+ or 3+ by IHC) in the preenrollment tumor sample, for the dose escalation cohort. NY-ESO expression must be confirmed at MDACC prior to study entry. 2. Patients with histologically confirmed synovial sarcoma (cohort 1) or myxoid/round cell liposarcoma (cohort 2), with an HLA-A\*02:01, HLA-A\*02:05 or HLA-A\*02:06 positive and a positive expression of NY-ESO-1 (\>/= 50% tumor cells 2+ or 3+ by IHC) in the pre-enrollment tumor sample, for the expansion cohorts. Archival samples will be permitted for screening. NY-ESO expression must be confirmed at MDACC prior to study entry. 3. Patients must meet disease-specific eligibility criteria (see below). 4. Patients must have relapsed or become refractory to standard of care treatment and must have received at least one prior line of systemic therapy including either doxorubicin and/or ifosfamide (synovial sarcoma and MRCLS) or trabectedin (MRCLS). 5. Patients must have measurable disease per the RECIST v1.1 at enrollment. 6. Patients must be at least 2 weeks from last cytotoxic chemotherapy at the time of first administration of lymphodepleting chemotherapy. Patients may continue tyrosine kinase inhibitors or other targeted therapies until at least 3 days prior to administration of lymphodepleting chemotherapy. 7. Patients must be at least 3 months from any cell therapy for malignancy. 8. Eastern Cooperative Oncology Group performance status 0-1 (Appendix A). 9. Adequate organ function at screening, as defined by the following: 1. Renal: Serum creatinine ≤ 1.5 mg/dL or estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration equation) ≥45 ml/min/1.73 m2 2. Hepatic: alanine transaminase (ALT)/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 and no ascites. 3. Cardiac: Cardiac ejection fraction ≥ 50%, no clinically significant pericardial effusion as determined by echocardiogram (ECHO) or multigated 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) 4. Pulmonary: No clinically significant pleural effusion (per principal investigator \[PI\] judgement), and baseline oxygen saturation ≥ 92% on room air, 5. Hematological: absolute neutrophil count (ANC) ≥ 1000/mm3, platelet count ≥ 75,000/mm3, and hemoglobin ≥ 8 g/dL 6. 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. 10. Able to provide written informed consent. 11. Aged 16-80 years. 12. Weight ≥40 kg. 13. All male and female patients who are able to have children must practice effective birth control while on study therapy and for up to 3 months post completion of study therapy. Acceptable forms of birth control for female patients include: hormonal birth control, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence. Female patients who become pregnant or suspect pregnancy must immediately notify their doctor. Females patients who become pregnant will be taken off study. Men who are able to have children must use effective birth control while on the study therapy. Acceptable forms of birth control for male patients include: condom with spermicide or abstinence. If the male patient fathers a child or suspects that