ACTengine® IMA203/IMA203CD8 as Monotherapy or in Combination With Nivolumab in Recurrent and/or Refractory Solid Tumors

Purpose

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).

Conditions

  • Refractory Cancer
  • Recurrent Cancer
  • Solid Tumor, Adult
  • Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Dose Escalation A (closed to enrollment) 		Dose escalation of IMA203
  • Biological: IMA203 Product
    The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula
    Other names:
    • anzutresgene autoleucel
    • anzu-cel
  • Device: IMADetect®
    IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials.
Experimental
Extension Cohort A 		IMA203 at RP2D
  • Biological: IMA203 Product
    The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula
    Other names:
    • anzutresgene autoleucel
    • anzu-cel
  • Biological: IMA203 product- flat dose
    The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells
    Other names:
    • anzutresgene autoleucel
    • anzu-cel
  • Device: IMADetect®
    IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials.
Experimental
Extension Cohort B (closed to enrollment) 		IMA203 at RP2D + nivolumab
  • Biological: IMA203 Product
    The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula
    Other names:
    • anzutresgene autoleucel
    • anzu-cel
  • Drug: Nivolumab
    Nivolumab will be given post IMA203/IMA203CD8 infusion, after hematologic recovery is achieved. Clinical supply provided by Bristol Myers Squibb.
    Other names:
    • Opdivo®
Experimental
Extension Cohort AA 		IMA203 at final RP2D (flat dose)
  • Biological: IMA203 product- flat dose
    The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells
    Other names:
    • anzutresgene autoleucel
    • anzu-cel
  • Device: IMADetect®
    IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials.
Experimental
Uveal Melanoma 		IMA203 at RP2D
  • Biological: IMA203 Product
    The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula
    Other names:
    • anzutresgene autoleucel
    • anzu-cel
  • Device: IMADetect®
    IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials.
Experimental
Dose Escalation B 		Dose escalation of IMA203CD8
  • Biological: IMA203CD8 Product
    The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula
  • Device: IMADetect®
    IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials.
Experimental
Extension Cohort C 		IMA203CD8 at dose levels confirmed to be safe
  • Biological: IMA203CD8 Product
    The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula
  • Device: IMADetect®
    IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials.
Experimental
Extension Cohort D 		IMA203CD8 at dose levels confirmed to be safe; without IL-2
  • Biological: IMA203CD8 Product
    The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula
  • Device: IMADetect®
    IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials.
Experimental
Ovarian 		IMA203CD8 monotherapy at dose levels confirmed to be safe
  • Biological: IMA203CD8 Product
    The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula
  • Device: IMADetect®
    IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials.
Experimental
Endometrial 		IMA203CD8 monotherapy at dose levels confirmed to be safe
  • Biological: IMA203CD8 Product
    The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula
  • Device: IMADetect®
    IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials.
Experimental
Head and Neck, Lung, and Triple Negative Breast Cancer 		IMA203CD8 monotherapy at dose levels confirmed to be safe
  • Biological: IMA203CD8 Product
    The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula
  • Device: IMADetect®
    IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials.
Experimental
Rare Cancers 		IMA203CD8 monotherapy at dose levels confirmed to be safe
  • Biological: IMA203CD8 Product
    The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula
  • Device: IMADetect®
    IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials.

Recruiting Locations

Massachusetts General Hospital
Boston 4930956, Massachusetts 6254926 02114
Contact:
Oldadapo O. Yeku, MD. PhD
617-643-6158

More Details

Status
Recruiting
Sponsor
Immatics US, Inc.

Study Contact

Immatics US, Inc.
+1 346 204-5400
ctgovinquiries@immatics.com

Detailed Description

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.