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History of Changes for Study: NCT03686124
TCR-engineered T Cells in 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 12, 2020 (v12)

Open or close this module Study Identification
Unique Protocol ID: IMA203-101
Brief Title: TCR-engineered T Cells in Solid Tumors (ACTengine)
Official Title: 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 Atezolizumab in Patients With Recurrent and/or Refractory Solid Tumors (ACTengine IMA203-101)
Secondary IDs:
Open or close this module Study Status
Record Verification: August 2020
Overall Status: Recruiting
Study Start: May 14, 2019
Primary Completion: September 2022 [Anticipated]
Study Completion: January 2024 [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 12, 2020
Last Update Posted: August 14, 2020 [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 product in patients with solid tumors that express preferentially expressed antigen in melanoma (PRAME).
Detailed Description:

SCREENING: Patient eligibility will be determined by HLA (human leukocyte antigen) screening and a biopsy for biomarker screening. If the patient is eligible, white blood cells will be taken during leukapheresis for the manufacture of the IMA203 product.

MANUFACTURING: IMA203 product will be made from the patient's white blood cells.

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

After the IMA203 product infusion, a low dose of IL-2 will be given subcutaneously twice daily for 14 days.

In group 2, atezolizumab will be administered every 4 weeks.

Patients will be monitored closely throughout the study. The treatment and observation phase ends 3 years post infusion.

Open or close this module Conditions
Conditions: Refractory Cancer
Recurrent Cancer
Solid Tumor, Adult
Cancer
Keywords: T-cell therapy
immunotherapy
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: 2
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 33 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: IMA203 Product
  • Pre-conditioning by non-myeloablative chemotherapy with Fludarabine and Cyclophosphamide
  • One dose of IMA203 product will be infused intravenously. Three dose levels will be evaluated. At least three patients per cohort will be treated.
  • Post-infusion of IMA203 product, administration of low dose recombinant human interleukin-2
Biological: IMA203 Product
Three dose levels (DL) of IMA203 product will be evaluated. 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: IMA203 Product + atezolizumab
  • Pre-conditioning by non-myeloablative chemotherapy with Fludarabine and Cyclophosphamide
  • One dose of IMA203 product will be infused intravenously. Two dose levels will be evaluated. At least three patients per cohort will be treated.
  • Post-infusion of IMA203 product, administration of low dose recombinant human interleukin-2
  • Treatment with atezolizumab: starting 2 lower doses every 2 weeks, followed by every 4 weeks for 1 year
Biological: IMA203 Product
Three dose levels (DL) of IMA203 product will be evaluated. 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: Atezolizumab
Atezolizumab group will be initiated after clearing the single arm for safety. Atezolizumab will be given post IMA203 infusion, after hematologic recovery is achieved, every 4 weeks for up to a year after IMA203 infusion.
Other Names:
  • Tecentriq
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Incidence of adverse events (AE)
[ Time Frame: up to 3 years post treatment ]

Secondary Outcome Measures:
1. Persistence of T-cells
[ Time Frame: up to 3 years post treatment ]

2. Tumor response per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and immune-related RECIST (irRECIST)
[ Time Frame: up to 12 months ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Pathologically confirmed advanced and/or metastatic solid tumor
  • Patients may enter screening procedure before, during, or after the last available indicated standard of care treatment. There is no limitation for prior anti cancer treatments.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • HLA phenotype positive
  • Measurable disease and accessible to biopsy
  • Adequate pulmonary function per protocol
  • Acceptable organ and bone marrow function per protocol
  • Acceptable coagulation status per protocol
  • Adequate hepatic function per protocol
  • Serum creatinine within normal range for age OR creatinine clearance with a recommended estimated glomerular filtration rate ≥ 50 mL/min/1.73 m2
  • Patient's tumor must express tumor antigen by qPCR using a fresh tumor biopsy specimen
  • Life expectancy more than 3 months
  • Confirmed availability of production capacities for IMA203 product
  • 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.
  • For hepatocellular carcinoma (HCC) patients only, Child-Pugh score of ≤ 6
  • IMA203 product must have passed all of the release tests
  • Female patient of childbearing potential must use adequate contraception prior to study entry until 12 months after the infusion of IMA203
  • Male patient must agree to use effective contraception or be abstinent while on study and for 6 months after the infusion of IMA203
  • Hepatocellular carcinoma (HCC) patients with liver cirrhosis only - upper endoscopy is required within 6 months of study entry
  • The patient must have recovered from any side effects of prior therapy to Grade 1 or lower (except for non-clinically significant toxicities; e.g., alopecia, vitiligo) prior to lymphodepletion. As determined by the investigator, the patient may still be eligible if the patient has not fully recovered from Grade ≥ 2 toxicities if these toxicities are not anticipated to further improve (e.g., chronic neuropathy) and such toxicities are not anticipated to worsen with the lymphodepletion therapy

Exclusion Criteria:

  • History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 3 years
  • Solid tumors with low likelihood of tumor biomarker expression per protocol
  • 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 hypersensitivity to cyclophosphamide (CY), fludarabine (FLU), or IL-2
  • History of or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician
  • HIV infection, active hepatitis B virus (HBV), active hepatitis C virus (HCV) infection, ongoing active anti-HCV treatment or detectable HBV or HCV viral load at the most recent laboratory report. Patients with both HBV and HCV infections will be excluded from screening
    1. Patients with a history of HCV infection and with an undetectable viral load per the most recent laboratory report and/or completed anti-HCV treatment but are HCV antibody positive are permitted.
    2. History of treated HBV infection is permitted if the viral load is undetectable per the most recent laboratory report. Note: HCC patients with controlled HBV infection, as defined by resolved (anti-hepatitis B surface antigen [HBs-Ag] antibody (Ab) negative, anti-core antigen [HBc Ag] Ab positive) or chronic stable (anti HBs-Ag Ab positive) HBV infection will be eligible for screening. Patients with active HBV infection who are not on anti-HBV treatment will be excluded.
  • Any condition contraindicating leukapheresis
  • Patients with active brain metastases

NOTE: Patients with a history of brain metastases may be eligible, if an imaging scan with contrast enhancement not older than 4 weeks is able to exclude the existence of currently active brain metastasis, and steroid therapy has been discontinued for ≥2 weeks.

• Treatment with protocol-defined excluded treatments, medical devices, and/or procedures per protocol

For atezolizumab treatment, patients must have adequate hematologic recovery, must have recovered from infections to Grade 1 or lower, and 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.).

Open or close this module Contacts/Locations
Central Contact Person: Jorge Rivas, M.D.
Telephone: 346-204-5350
Email: ctgovinquiries@immatics.com
Study Officials: Apostolia Tsimberidou, M.D., Ph.D.
Principal Investigator
MDACC, Houston, TX
Cedrik Britten, M.D.
Study Director
Immatics US, Inc.
Locations: United States, Pennsylvania
University of Pittsburgh Medical Center
[Recruiting]
Pittsburgh, Pennsylvania, United States, 15232
Contact:Contact: Jason Luke, M.D.
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: Apostolia Tsimberidou, M.D., Ph.D.
Contact:Principal Investigator: Apostolia Tsimberidou, M.D., Ph.D.
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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