TCR1188-ABC Cells in KRAS-mutated Cancers

Prior treatment

• Active invasive cancer, other than the proposed cancer included in the study, within 2 years prior to eligibility confirmation by a physician-investigator. \[Note: non-invasive cancers treated with curative intent (e.g., non-melanoma skin cancer) may still be eligible\].
• Patients requiring chronic treatment with systemic steroids or immunosuppressant medications. Low-dose physiologic replacement therapy with corticosteroids equivalent to prednisone 10 mg/day or lower, topical steroids and inhaled steroids are acceptable. For additional details regarding use of steroid and immunosuppressant medications, please see Section 5.6.
• Prior history of myocarditis.

Other illness

• Active hepatitis B or hepatitis C infection
• Any other active, uncontrolled infection.
• Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 5).
• Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg daily of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
• Patients with unstable angina, serious uncontrolled cardiac arrhythmia, and/or myocardial infarction within 6 months of physician-investigator confirmation of eligibility.
• Patients with pneumonitis/interstitial lung disease requiring steroid treatment.
• Patients with active/untreated brain metastases. \[Note: History of treated metastases may still be eligible.\]

Lab values

• Patients with a severe acquired or inherited immunodeficiency, including HIV positive patients with a CD4 count ≤ 350 cells/μL. In order to qualify, HIV positive patients must also be on an established antiretroviral therapy regimen with a viral load of \<400 copies/mL.
• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40) or tocilizumab.

Other

• Severe, active co-morbidity that in the opinion of the physician-investigator would preclude participation in the study.
• Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods, as described in protocol Section 4.3.

• 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