TCR-engineered T Cells in Solid Tumors (ACTengine IMA201-101)

Inclusion Criteria

• Patient ≥ 18 years of age
• Pathologically confirmed advanced and/or metastatic solid tumor
• Patients may enter screening procedure before, during, or after the last available indicated standard of care treatment. There is no limitation for prior anti cancer treatments.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• HLA phenotype positive for the study
• Patients must have measurable disease according to RECIST 1.1
• Disease accessible to biopsy
• Adequate pulmonary function per protocol
• Adequate organ and bone marrow function per protocol
• Acceptable coagulation status per protocol
• Adequate hepatic function per protocol
• Adequate renal function per protocol
• Patient's tumor must express tumor antigen by qPCR using a fresh tumor biopsy specimen
• Life expectancy more than 3 months
• Confirmed availability of production capacities for IMA201 product
• Patients must have recurrent/progressing and/or refractory solid tumors and must have received or not be eligible for all available indicated standard of care treatment.
• For hepatocellular carcinoma (HCC) patients only, Child-Pugh score of ≤ 6
• IMA201 product must have passed all of the release tests
• Female patient of childbearing potential must use adequate contraception prior to study entry until 12 months after the infusion of IMA201
• Male patient must agree to use effective contraception or be abstinent while on study and for 6 months after the infusion of IMA201
• The patient must have recovered from any side effects of prior therapy to Grade 1 or lower (except for non-clinically significant toxicities; e.g., alopecia, vitiligo) prior to lymphodepletion. As determined by the investigator, the patient may still be eligible if the patient has not fully recovered from Grade ≥ 2 toxicities if these toxicities are not anticipated to further improve (e.g., chronic neuropathy) and such toxicities are not anticipated to worsen with the lymphodepletion therapy

Exclusion Criteria

• History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 3 years
• Solid tumors with low likelihood of tumor biomarker expression per protocol
• Pregnant or breastfeeding
• Serious autoimmune disease Note: At the discretion of the investigator, these patients may be included if their disease is well controlled without the use of immunosuppressive agents.
• History of cardiac conditions as per protocol
• Prior stem cell transplantation or solid organ transplantation
• Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study
• History of hypersensitivity to cyclophosphamide (CY), fludarabine (FLU), or IL-2, or to any of the rescue medications
• History of or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician
• HIV infection, active hepatitis B virus (HBV), active hepatitis C virus (HCV) infection, ongoing active anti-HCV treatment or detectable HBV or HCV viral load at the most recent laboratory report. Patients with both HBV and HCV infections will be excluded from screening
• Patients with a history of HCV infection and with an undetectable viral load per the most recent laboratory report and/or completed anti-HCV treatment but are HCV antibody positive are permitted.
• History of treated HBV infection is permitted if the viral load is undetectable per the most recent laboratory report. Note: HCC patients with controlled HBV infection, as defined by resolved (anti-hepatitis B surface antigen [HBs-Ag] antibody (Ab) negative, anti-core antigen [HBc Ag] Ab positive) or chronic stable (anti HBs-Ag Ab positive) HBV infection will be eligible for screening. Patients with active HBV infection who are not on anti-HBV treatment will be excluded.
• Any condition contraindicating leukapheresis, lymphodepletion, low-dose IL-2, and/or IMA201 treatment
• Patients with any active viral infection
• Patients with active brain metastases NOTE: Patients with a history of brain metastases may be eligible, if an imaging scan with contrast enhancement not older than 4 weeks is able to exclude the existence of currently active brain metastasis, and steroid therapy has been discontinued for ≥2 weeks.
• Treatment with protocol-defined excluded treatments, medical devices, and/or procedures per protocol
• Concurrent participation in an interventional part of another clinical trial