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History of Changes for Study: NCT03686124
ACTengine® IMA203/IMA203CD8 as Monotherapy or in Combination With Nivolumab in Recurrent and/or Refractory Solid Tumors (ACTengine)
Latest version (submitted October 23, 2023) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 September 25, 2018 None (earliest Version on record)
2 October 4, 2018 Study Status
3 March 14, 2019 Study Status and Oversight
4 April 22, 2019 Recruitment Status, Study Status and Contacts/Locations
5 April 26, 2019 Contacts/Locations and Study Status
6 June 6, 2019 Study Status
7 June 21, 2019 Contacts/Locations and Study Status
8 July 12, 2019 Contacts/Locations and Study Status
9 December 12, 2019 Study Status and Study Description
10 January 10, 2020 Study Status
11 February 26, 2020 Study Status and Contacts/Locations
12 August 12, 2020 Outcome Measures, Arms and Interventions, Contacts/Locations, Study Status, Study Design, Eligibility, Study Description, Sponsor/Collaborators and Study Identification
13 September 3, 2020 Study Status and Contacts/Locations
14 April 8, 2021 Study Status and Contacts/Locations
15 July 7, 2021 Arms and Interventions, Contacts/Locations, Study Description, Study Status, Eligibility, Study Design and Study Identification
16 August 19, 2021 Study Status and Contacts/Locations
17 September 10, 2021 Contacts/Locations and Study Status
18 May 24, 2022 Arms and Interventions, Study Status, Outcome Measures, Study Description, Study Identification and Eligibility
19 August 11, 2022 Outcome Measures, Arms and Interventions, Contacts/Locations, Study Description, Study Status, Eligibility, Study Design and Study Identification
20 February 2, 2023 Study Status and Contacts/Locations
21 August 21, 2023 Arms and Interventions, Contacts/Locations, Study Status, Eligibility, Study Design, Conditions and Study Description
22 October 23, 2023 Study Status and Contacts/Locations
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Study NCT03686124
Submitted Date:  August 21, 2023 (v21)

Open or close this module Study Identification
Unique Protocol ID: IMA203-101
Brief Title: ACTengine® IMA203/IMA203CD8 as Monotherapy or in Combination With Nivolumab in Recurrent and/or Refractory Solid Tumors (ACTengine)
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
Secondary IDs:
Open or close this module Study Status
Record Verification: August 2023
Overall Status: Recruiting
Study Start: May 14, 2019
Primary Completion: December 2028 [Anticipated]
Study Completion: December 2028 [Anticipated]
First Submitted: September 25, 2018
First Submitted that
Met QC Criteria:
September 25, 2018
First Posted: September 26, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:
August 21, 2023
Last Update Posted: August 23, 2023 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Immatics US, Inc.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: Yes
Unapproved/Uncleared Device: Yes
Pediatric Postmarket Surveillance:
Data Monitoring: Yes
Open or close this module Study Description
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).
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.

Open or close this module Conditions
Conditions: Refractory Cancer
Recurrent Cancer
Solid Tumor, Adult
Cancer
Keywords: T-cell therapy
immunotherapy
Melanoma (Skin)
Melanoma, Uveal
Ovarian Carcinoma
Uterine Carcinoma
Uterine Carcinosarcoma
Immatics
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Parallel Assignment
Number of Arms: 5
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 186 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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 Names:
  • 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.
Open or close this module Outcome Measures
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)
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
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

Open or close this module Contacts/Locations
Central Contact Person: Immatics US, Inc.
Telephone: +1 346 204-5400
Email: ctgovinquiries@immatics.com
Study Officials: Cedrik Britten, M.D.
Study Director
Immatics US, Inc.
Locations: United States, Florida
University of Miami Hospital and Clinics
[Recruiting]
Miami, Florida, United States, 33136
Contact:Contact: 305-243-2647 CRSCutaneous@miami.edu
United States, New York
Columbia University Medical Center
[Recruiting]
New York, New York, United States, 10032
Contact:Contact: 212-342-5162 cancerclinicaltrials@cumc.columbia.edu
Contact:Principal Investigator: Ran Reshef, MD
United States, Pennsylvania
University of Pittsburgh Medical Center
[Recruiting]
Pittsburgh, Pennsylvania, United States, 15232
Contact:Contact: Jason Luke, M.D. 412-623-6132 lukejj@upmc.edu
Contact:Principal Investigator: Jason Luke, M.D.
United States, Texas
University of Texas MD Anderson Cancer Center
[Recruiting]
Houston, Texas, United States, 77030
Contact:Contact: Dejka M Araujo, M.D. 713-792-3626 daraujo@mdanderson.org
Contact:Principal Investigator: Dejka M Araujo, M.D.
Germany
Charité Benjamin Franklin - Klinik für Hämatologie und Onkologie
[Active, not recruiting]
Berlin, Germany, 12203
Universitätsklinikum Hamburg-Eppendorf
[Recruiting]
Hamburg, Germany, 20246
Germany, Bavaria
Universitätsklinikum Würzburg
[Recruiting]
Würzburg, Bavaria, Germany, 97080
Germany, North Rhine-Westphalia
Universitätsklinikum Bonn - Medizinische Klinik III
[Recruiting]
Bonn, North Rhine-Westphalia, Germany, 53127
Germany, Saxony
Universitätsklinikum C.-G.-Carus Dresden
[Recruiting]
Dresden, Saxony, Germany, 01307
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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