TCR1188-ABC Cells in KRAS-mutated Cancers

Inclusion Criteria:

1. Patients ≥ 18 years of age

2. Patients with one of the following diagnoses:

   1. Histologically confirmed metastatic pancreatic adenocarcinoma or cholangiocarcinoma
   2. Histologically confirmed metastatic colorectal cancer
   3. Histologically confirmed metastatic non-small cell lung cancer
3. HLA-A*11:01 positive as confirmed by a CLIA certified laboratory.
4. KRAS G12V mutation positive disease as confirmed on tissue, blood, or plasma by next generation sequencing by a CLIA certified laboratory.

5. Received prior treatment for their primary malignancy as follows:

   1. 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.
   2. 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.
   3. Non-Small Cell Lung Cancer Patients: At least one prior line of standard of care therapy for advanced stage disease.
6. Evidence of radiographically detectable disease within 8 weeks of physician-investigator confirmation of eligibility.

7. Adequate organ function within 4 weeks of eligibility confirmation by a physician-investigator defined as:

   1. Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 50 cc/min per the Cockcroft-Gault Equation; Patient must not be on dialysis.
   2. ALT/AST ≤ 5 x ULN (patients with liver metastases) or ALT/AST ≤ 2.5 x ULN (patients without liver metastases)
   3. 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)
   4. Left Ventricle Ejection Fraction (LVEF) ≥ 50% confirmed by ECHO/MUGA
   5. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen > 92% on room air

8. 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:

   1. Hemoglobin ≥ 8 g/dL
   2. Absolute neutrophil count ≥ 1000/μL
   3. Platelet count ≥ 100,000/μL
9. ECOG Performance Status that is either 0 or 1.
10. Signed, written informed consent

Exclusion Criteria:

• 1. Active hepatitis B or hepatitis C infection 2. 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.

  3. Any other active, uncontrolled infection. 4. Class III/IV cardiovascular disability according to the New York Heart Association Classification.

  5. Severe, active co-morbidity that in the opinion of the physician-investigator would preclude participation in the study.

  6. 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].

  7. Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods.

  8. 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.

  9. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg daily of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.

  10. Patients with unstable angina, serious uncontrolled cardiac arrhythmia, and/or mycocardial infarction within 6 months of physician-investigator confirmation of eligibility.

  11. Prior history of myocarditis. 12. Patients with pneumonitis/interstitial lung disease requiring steroid treatment.

  13. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40) or tocilizumab.