Phase I, Open-Label Study of Autologous Mutant KRAS and ILT4-Redirected T-cell Receptor Cells (TCR1188-ABC)
This is a Phase I, open-label dose finding study to assess the safety, manufacturing feasibility, and preliminary efficacy of TCR1188-ABC cells in patients with KRAS-mutated cancers. Initially, patients with KRAS G12V mutation positive metastatic pancreatic adenocarcinoma, cholangiocarcinoma, colorectal cancer, or non-small cell lung cancer (NSCLC) will be targeted for participation. Up to 4 total dose levels will be evaluated using a 3+3 dose escalation design.
• Patients ≥ 18 years of age
• Patients with one of the following diagnoses:
∙ Histologically confirmed metastatic pancreatic adenocarcinoma or cholangiocarcinoma
‣ Histologically confirmed metastatic colorectal cancer
‣ Histologically confirmed metastatic non-small cell lung cancer
• HLA-A\*11:01 positive as confirmed by a CLIA certified laboratory.
• KRAS G12V mutation positive disease as confirmed on tissue, blood, or plasma by next generation sequencing by a CLIA certified laboratory.
• Received prior treatment for their primary malignancy as follows:
∙ Pancreatic Cancer/Cholangiocarcinoma Patients: At least one prior line of standard of care therapy for advanced stage disease. For pancreatic cancer patients, this must include a gemcitabine or fluorouracil (5 FU)-based regimen.
‣ Colorectal Cancer Patients: At least three prior lines of standard of care therapy for advanced stage disease. Prior treatment must include all of the following unless the patient was ineligible for a specific therapy type: i). a fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy regimen, ii). an anti-vascular endothelial growth factor (VEGF) agent, and iii). regorafenib, trifluridine-tipiracil, or fruquintinib. Patients with microsatellite instability-high (MSI-H) disease must also have received, or be ineligible for, prior treatment with an immune checkpoint inhibitor.
‣ Non-Small Cell Lung Cancer Patients: At least one prior line of standard of care therapy for advanced stage disease.
• Evidence of radiographically detectable disease within 8 weeks of physician-investigator confirmation of eligibility.
• Adequate organ function within 4 weeks of eligibility confirmation by a physician-investigator defined as:
∙ Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 50 cc/min per the Cockcroft-Gault Equation; Patient must not be on dialysis.
‣ ALT/AST ≤ 5 x ULN (patients with liver metastases) or ALT/AST ≤ 2.5 x ULN (patients without liver metastases)
‣ Total bilirubin ≤ 1.5 mg/dL x ULN, unless the subject has Gilbert's syndrome (if so, direct bilirubin must be ≤ 2.0 mg/dL x ULN)
‣ Left Ventricle Ejection Fraction (LVEF) ≥ 50% confirmed by ECHO/MUGA
‣ Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen \> 92% on room air
• Patients must have adequate hematologic reserve within 4 weeks of eligibility confirmation by a physician-investigator and must not be dependent on transfusions to maintain these hematologic parameters. Adequate hematologic reserve is defined as:
∙ Hemoglobin ≥ 8 g/dL
‣ Absolute neutrophil count ≥ 1000/μL
‣ Platelet count ≥ 100,000/μL
• ECOG Performance Status that is either 0 or 1.
⁃ Signed, written informed consent