Phase 1 Study Evaluating Genetically Modified Autologous T Cells Expressing a T-cell Receptor Recognizing a Cancer/Germline Antigen in Patients With Recurrent and/or Refractory Solid Tumors (ACTengine® IMA201-101)
The study purpose is to establish the safety and tolerability of IMA201 in patients with solid tumors that express melanoma-associated antigen 4 or 8 (MAGEA4/8.
MANUFACTURING: IMA201 product will be made from the patient's white blood cells.
TREATMENT: Lymphodepletion with cyclophosphamide and fludarabine will occur in the days before the IMA201 infusion to improve the duration of time that IMA201 stays in the body.
After IMA201 infusion, a low dose of IL-2 will be given twice daily for a period of time.
Patients will be closely monitored for safety and for a total of 3 years post IMA201 infusion.
18 Years and up
Accepting Healthy Volunteers?
- 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 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
- 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
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
- 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