Phase 1 study evaluating genetically modified autologous T cells expressing a T cell recepter recognizing a cancer/germline Antigen in patients with recurrent and/or refractory solid Tumors (ACTengine IMA203-101)
Phase I, , Monozentrisch, National
>= 18 Jahre
Inclusion Criteria: 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 Measurable disease and accessible to biopsy Adequate pulmonary function per protocol Acceptable organ and bone marrow function per protocol Acceptable coagulation status per protocol Adequate hepatic function per protocol Serum creatinine within normal range for age OR creatinine clearance with a recommended estimated glomerular filtration rate ≥ 50 mL/min/1.73 m2 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 IMA203 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 IMA203 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 IMA203 Male patient must agree to use effective contraception or be abstinent while on study and for 6 months after the infusion of IMA203 Hepatocellular carcinoma (HCC) patients with liver cirrhosis only - upper endoscopy is required within 6 months of study entry 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 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 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 For atezolizumab treatment, patients must have adequate hematologic recovery, must have recovered from infections to Grade 1 or lower, and must not have a history of severe immune-related toxicities, defined as any Grade 3 or 4 toxicities related to prior PD1/PD-L1 inhibitor therapy (e.g., atezolizumab, pembrolizumab or nivolumab etc.).