The study purpose is to establish the safety and tolerability of IMA203 product with or
without combination with atezolizumab in patients with solid tumors that express
preferentially expressed antigen in melanoma (PRAME).
SCREENING: Patient eligibility will be determined by protocol inclusion/exclusion criteria
including HLA (human leukocyte antigen) screening and a biopsy for biomarker screening. If
the patient is eligible, white blood cells will be taken during leukapheresis for the
manufacture of the IMA203 product.
MANUFACTURING: IMA203 product will be made from the patient's white blood cells.
TREATMENT: Lymphodepletion with cyclophosphamide and fludarabine will occur in the days
before the IMA203 product infusion to improve the duration of time that IMA203 product stays
in the body. The patient will be admitted to the hospital during the T-cell infusion.
After the IMA203 product infusion, a low dose of IL-2 will be given subcutaneously daily for
10 days.
In Extension Cohort B (IMA203 plus atezolizumab), atezolizumab will be administered for up to
one year.
Patients will be monitored closely throughout the study. The treatment and observation phase
ends 3 years post infusion.
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 for the study
- Measurable disease and 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 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 or
any of these 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
IMA203 treatment
- 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.
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.).
