UPCC 37824 Phase 1 study evaluating genetically modified autologous T cells expressing a T-cell receptor recognizing a cancer/germline antigen as monotherapy or in combination with nivolumab in patients with recurrent and/or refractory solid tumors (ACTengine® IMA203-101) (ACTengine)

Study of Genetically Modified T Cells for Solid Tumors

Enrolling By Invitation
18 years or above
All
Phase 1/2
375 participants needed
1 Location

Brief description of study

The study's purpose is to establish the safety and tolerability of IMA203/IMA203CD8 products with or without combination with nivolumab in patients with solid tumors that express preferentially expressed antigen in melanoma (PRAME).

Detailed description of study

SCREENING: Patient eligibility will be determined by protocol inclusion/exclusion criteria including HLA (human leukocyte antigen) screening and a biopsy (or collection of archival tumor tissue) for biomarker screening. If the patient is eligible, white blood cells will be taken during leukapheresis for the manufacture of IMA203 or IMA203CD8 product.

MANUFACTURING: IMA203 or IMA203CD8 products will be made from the patients' white blood cells.

TREATMENT: Lymphodepletion with cyclophosphamide and fludarabine will occur in the days before the IMA203/IMA203CD8 product infusion to improve the duration of time that IMA203/IMA203CD8 product stays in the body. The patient will be admitted to the hospital during the T-cell infusion.

After the IMA203/IMA203CD8 product infusion, if applicable, a low dose of IL-2 will be given subcutaneously until day 10.

In Extension Cohort B (IMA203) nivolumab will be administered intravenously.

Patients will be monitored closely throughout the study. The follow-up phase ends 5 years post infusion.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Refractory Cancer, Recurrent Cancer, Solid Tumor, Adult, Cancer
  • Age: 18 years or above
  • Gender: All

Inclusion Criteria:

  • 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.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • HLA-A*02:01 positive
  • For patients with ovarian/fallopian tube cancer only: Patients must have confirmed diagnosis of high-grade serous or endometrioid epithelial ovarian cancer (EOC), primary peritoneal cancer, or fallopian tube cancer.
  • For patients with endometrial carcinoma only: Patients must have a histologically confirmed diagnosis of recurrent or persistent endometrial carcinoma.
  • Measurable disease according to RECIST 1.1
  • Adequate selected organ function per protocol
  • Patient's tumor must express tumor antigen by "IMADetect® RT-qPCR. Retrospective testing will be required for patients that qualify.
  • Life expectancy more than 5 months
  • Female patient of childbearing potential must use adequate contraception prior to study entry until 12 months after the infusion of IMA203/IMA203CD8
  • Male patient must agree to use effective contraception or be abstinent while on study and for 6 months after the infusion of IMA203/IMA203CD8
  • The patient must have recovered from any side effects of prior therapy to Grade 1 or lower prior to lymphodepletion.

Exclusion Criteria:

  • History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 3 years
  • 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 or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician
  • Positive for HIV infection or with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
  • Patients with LDH greater than 2.0-fold ULN.
  • Any condition contraindicating leukapheresis, lymphodepletion, low-dose IL-2, and/or IMA203/IMA203CD8 treatment
  • Patients with active brain metastases
  • Concurrent treatment in another clinical trial.
  • For nivolumab treatment, patients 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.).

Other protocol defined inclusion/exclusion criteria could apply

This study investigates the safety and tolerability of genetically modified autologous T cells in patients with recurrent or refractory solid tumors. The T cells are engineered to express a receptor that recognizes a specific cancer-related protein called PRAME, which is often found in melanoma and other solid tumors. The study will explore the use of these modified T cells alone or in combination with another investigational medication to determine the best approach for treatment.

Participants will undergo a series of procedures, starting with a screening process that includes genetic testing and tumor tissue analysis to confirm eligibility. Eligible participants will have their white blood cells collected to manufacture the modified T cells. Before receiving the T cell infusion, participants will undergo a process called lymphodepletion to prepare their bodies. The T cell infusion will be administered in a hospital setting, followed by a low dose of IL-2 to support the treatment process. In some cases, participants may also receive an additional investigational medication intravenously.

  • Who can participate: Adults with recurrent or refractory solid tumors who have received or are ineligible for standard treatments can participate. They must have a performance status of 0-1, be HLA-A*02:01 positive, and have a life expectancy of more than 5 months.
  • Study details: Participants will have blood drawn for T cell manufacturing and receive a T cell infusion following lymphodepletion. Some may also receive an investigational medication intravenously. A placebo is not used in this study.
  • Study timelines: The study will last 5 years post infusion.
Updated on 13 May 2026. Study ID: 25-0046
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