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

  1. 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.
  2. 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