ACTengine® IMA203/IMA203CD8 as Monotherapy or in Combination With Nivolumab in Recurrent and/or Refractory Solid Tumors
- Conditions
- Solid Tumor, AdultRefractory CancerRecurrent CancerCancer
- Interventions
- Biological: IMA203 ProductBiological: IMA203 product- flat doseBiological: IMA203CD8 ProductDevice: IMADetect®
- Registration Number
- NCT03686124
- Lead Sponsor
- Immatics US, Inc.
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 375
- 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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose Escalation A (closed to enrollment) IMA203 Product Dose escalation of IMA203 Dose Escalation A (closed to enrollment) IMADetect® Dose escalation of IMA203 Extension Cohort A IMA203 Product IMA203 at RP2D Extension Cohort A IMADetect® IMA203 at RP2D Extension Cohort B (closed to enrollment) IMA203 Product IMA203 at RP2D + nivolumab Extension Cohort B (closed to enrollment) Nivolumab IMA203 at RP2D + nivolumab Extension Cohort AA IMA203 product- flat dose IMA203 at final RP2D (flat dose) Extension Cohort AA IMADetect® IMA203 at final RP2D (flat dose) Uveal Melanoma IMA203 Product IMA203 at RP2D Uveal Melanoma IMADetect® IMA203 at RP2D Dose Escalation B IMA203CD8 Product Dose escalation of IMA203CD8 Dose Escalation B IMADetect® Dose escalation of IMA203CD8 Extension Cohort C IMA203CD8 Product IMA203CD8 at dose levels confirmed to be safe Extension Cohort C IMADetect® IMA203CD8 at dose levels confirmed to be safe Extension Cohort D IMA203CD8 Product IMA203CD8 at dose levels confirmed to be safe; without IL-2 Extension Cohort D IMADetect® IMA203CD8 at dose levels confirmed to be safe; without IL-2 Ovarian IMA203CD8 Product IMA203CD8 monotherapy at dose levels confirmed to be safe Ovarian IMADetect® IMA203CD8 monotherapy at dose levels confirmed to be safe Endometrial IMA203CD8 Product IMA203CD8 monotherapy at dose levels confirmed to be safe Endometrial IMADetect® IMA203CD8 monotherapy at dose levels confirmed to be safe Head and Neck, Lung, and Triple Negative Breast Cancer IMA203CD8 Product IMA203CD8 monotherapy at dose levels confirmed to be safe Head and Neck, Lung, and Triple Negative Breast Cancer IMADetect® IMA203CD8 monotherapy at dose levels confirmed to be safe Rare Cancers IMA203CD8 Product IMA203CD8 monotherapy at dose levels confirmed to be safe Rare Cancers IMADetect® IMA203CD8 monotherapy at dose levels confirmed to be safe
- Primary Outcome Measures
Name Time Method Phase 1: Determine the MTD and/or recommended dose for extension for IMA203/IMA203CD8 28 days Number of patients with dose-limiting toxicities (DLTs)
Phase 1 and Phase 2: Number and grade of treatment emergent adverse events and adverse events of special interest in subjects treated. 35 days Treatment emergent adverse events (TEAEs), Adverse events of special interest (AESIs) and Treatment-emergent serious adverse events (TESAEs).
Phase 1 and Phase 2: Tumor Response 5 years Objective response rate (ORR) based on best overall response (BOR) of complete response (CR) and partial response (PR) centrally assessed (by a BICR1) using RECIST1.1
- Secondary Outcome Measures
Name Time Method Phase 1 and 2: Persistence of TCR engineered T-cells up to 5 years post treatment Measurement of TCR-engineered T cells in peripheral blood
Phase 1 and 2: Tumor response up to 5 years Overall response rate, duration of response, disease control rate and progression free survival based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Overall survival.
Phase 2: Patient reported quality of life up to 5 years Quality of Life questionnaires (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and EuroQol 5-Dimension 5-Level questionnaire). Higher score indicates worsening of patient's condition.
Trial Locations
- Locations (15)
University of Miami Hospital and Clinics
🇺🇸Miami, Florida, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Ohio State University Wexner Medical Center Gynecologic Oncology at Mill Run
🇺🇸Columbus, Ohio, United States
University of Pennsylvania, Perelamn Center for Advanced Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Universitätsklinikum Heidelberg, Nationales Centrum für Tumorerkrankungen (NCT)
🇩🇪Heidelberg, Baden-Wurttemberg, Germany
Klinikum rechts der Isar der Technischen Universität München
🇩🇪Munich, Bavaria, Germany
Universitätsklinikum Würzburg
🇩🇪Würzburg, Bavaria, Germany
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