KRAS G12D-specific Immune Effector Cells Targeting KRAS G12D-positive Solid Tumors

The purpose of this study is to assess the feasibility, safety and efficacy of KRAS G12D-specific engineered immune effector (EIE) therapy in patients with advanced, KRAS G12D-positive malignancies. Another goal of the study is to characterize the function, expansion and persistence of KRAS G12D-specific effector cells in treated patients.

Inclusion Criteria: 1. Abilities to understand and the willingness to provide written informed consent; 2. ≥ 18 and ≤ 75 years old; 3. Histologically confirmed recurrent, refractory or metastatic advanced malignancies with documented KRAS G12D somatic mutation and measurable lesions by RECIST v1.1; patients have progressed after at least one line of standard of care systemic therapy for their malignancy. At time of leukapheresis, patients are either off dexamethasone or receiving dexamethasone ≤ 4 mg/day; 4. ECOG performance status 0-2 (or Karnofsky performance score ≥ 60); 5. Life expectancy \>3 months; 6. Satisfactory bone marrow, liver and kidney functions as defined by the following: absolute neutrophile count ≥ 1500/mm\^3; hemoglobin \> 10 g/dL; platelets \> 100000 /mm\^3; Bilirubin \< 1.5×ULN; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \< 2.5×ULN; creatinine \< 1.5×ULN; 7. Peripheral blood absolute lymphocyte count must be above 0.8×10\^9/L; 8. Satisfactory heart functions; 9. Must be willing to follow the instructions of doctors; 10. Women of reproductive potential (between 15 and 49 years old) must have a negative pregnancy test within 7 days of study start. Male and female patients of reproductive potential must agree to use birth control during the study and 3 months post study. Exclusion Criteria: 1. Receipt of KRAS G12D based therapy within 8 weeks prior to study entry; 2. HIV positive; 3. Tuberculosis infection not under control; 4. History of autoimmune disease, or other diseases requiring long-term administration of steroids or immunosuppressive therapies; 5. History of allergic disease, or allergy to immune cells or study product; 6. Patients already actively enrolled in other immune cell clinical study; 7. Presence of untreated or actively progressing central nervous system metastases not locally controlled; 8. Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.