The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03686124
Recruitment Status : Recruiting
First Posted : September 26, 2018
Last Update Posted : October 25, 2023
Sponsor:
Information provided by (Responsible Party):
Immatics US, Inc.

Brief Summary:
The study 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).

Condition or disease Intervention/treatment Phase
Refractory Cancer Recurrent Cancer Solid Tumor, Adult Cancer Biological: IMA203 Product Biological: IMA203CD8 Product Device: IMADetect® Drug: nivolumab (Opdivo®) Phase 1

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 an IMA203 or an IMA203CD8 product.

MANUFACTURING: IMA203 and 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, a low dose of IL-2 will be given subcutaneously daily for 10 days.

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 186 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Study Evaluating Genetically Modified Autologous T Cells Expressing a TCR Recognizing a Cancer/Germline Antigen as Monotherapy or in Combination With Nivolumab in Patients With Recurrent and/or Refractory Solid Tumors
Actual Study Start Date : May 14, 2019
Estimated Primary Completion Date : December 2028
Estimated Study Completion Date : December 2028


Arm Intervention/treatment
Experimental: Dose Escalation A
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.

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. IMADetect® is intended for investigational use only.

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.

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. IMADetect® is intended for investigational use only.

Experimental: Extension Cohort B
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.

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. IMADetect® is intended for investigational use only.

Drug: nivolumab (Opdivo®)
Nivolumab will be given post IMA203 infusion, after hematologic recovery is achieved. Clinical supply provided by Bristol Myers Squibb.
Other Name: Opdivo®

Experimental: Extension Cohort C
IMA203CD8 at provisional RP2D
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. IMADetect® is intended for investigational use only.

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. IMADetect® is intended for investigational use only.




Primary Outcome Measures :
  1. Evaluate safety and tolerability of treatment with treatment with ACTengine® IMA203/IMA203CD8 products as monotherapy or in combination with nivolumab [ Time Frame: 35 days ]
    Treatment emergent adverse events

  2. Determine the MTD and/or recommended dose for extension for IMA203/IMA203CD8 [ Time Frame: 28 days ]
    Number of patients with dose-limiting toxicities (DLTs)


Secondary Outcome Measures :
  1. Persistence of T-cells [ Time Frame: up to 5 years post treatment ]
    Measurement of TCR-engineered T cells in peripheral blood

  2. Tumor response [ Time Frame: up to 12 months ]
    Response Evaluation Criteria In Solid Tumors (RECIST) 1.1

  3. Tumor response [ Time Frame: up to 12 months ]
    Immune-Related Response Evaluation Criteria In Solid Tumors (irRECIST)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 phenotype positive for the study
  • Measurable disease according to RECIST 1.1
  • Adequate selected organ function per protocol
  • Patient's tumor must express tumor antigen by "IMADetect® RT-qPCR
  • Life expectancy more than 3 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 2.5-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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03686124


Contacts
Layout table for location contacts
Contact: Immatics US, Inc. +1 346 204-5400 ctgovinquiries@immatics.com

Locations
Layout table for location information
United States, Florida
University of Miami Hospital and Clinics Recruiting
Miami, Florida, United States, 33136
Contact    305-243-2647    CRSCutaneous@miami.edu   
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact    212-342-5162    cancerclinicaltrials@cumc.columbia.edu   
Principal Investigator: Ran Reshef, MD         
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Jason Luke, M.D.    412-623-6132    lukejj@upmc.edu   
Principal Investigator: Jason Luke, M.D.         
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Dejka M Araujo, M.D.    713-792-3626    daraujo@mdanderson.org   
Principal Investigator: Dejka M Araujo, M.D.         
Germany
Universitätsklinikum Würzburg Recruiting
Würzburg, Bavaria, Germany, 97080
Universitätsklinikum Bonn - Medizinische Klinik III Recruiting
Bonn, North Rhine-Westphalia, Germany, 53127
Universitätsklinikum C.-G.-Carus Dresden Recruiting
Dresden, Saxony, Germany, 01307
Charité Benjamin Franklin - Klinik für Hämatologie und Onkologie Recruiting
Berlin, Germany, 12203
Universitätsklinikum Hamburg-Eppendorf Recruiting
Hamburg, Germany, 20246
Sponsors and Collaborators
Immatics US, Inc.
Investigators
Layout table for investigator information
Study Director: Cedrik Britten, M.D. Immatics US, Inc.
Layout table for additonal information
Responsible Party: Immatics US, Inc.
ClinicalTrials.gov Identifier: NCT03686124    
Other Study ID Numbers: IMA203-101
First Posted: September 26, 2018    Key Record Dates
Last Update Posted: October 25, 2023
Last Verified: October 2023

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Keywords provided by Immatics US, Inc.:
T-cell therapy
immunotherapy
Melanoma (Skin)
Melanoma, Uveal
Ovarian Carcinoma
Uterine Carcinoma
Uterine Carcinosarcoma
Immatics
Additional relevant MeSH terms:
Layout table for MeSH terms
Recurrence
Disease Attributes
Pathologic Processes
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action