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TCR-engineered T Cells in Solid Tumors (ACTengine)

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ClinicalTrials.gov Identifier: NCT03686124
Recruitment Status : Recruiting
First Posted : September 26, 2018
Last Update Posted : September 14, 2021
Sponsor:
Information provided by (Responsible Party):
Immatics US, Inc.

Brief Summary:
The study purpose is to establish the safety and tolerability of IMA203 product with or without combination with atezolizumab 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 Device: IMADetect® Drug: Atezolizumab Phase 1

Detailed Description:

SCREENING: Patient eligibility will be determined by protocol inclusion/exclusion criteria including 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 daily for 10 days.

In Extension Cohort B (IMA203 plus atezolizumab), atezolizumab will be administered for up to one year.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 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 Atezolizumab in Patients With Recurrent and/or Refractory Solid Tumors
Actual Study Start Date : May 14, 2019
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : January 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose Escalation
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 MTD
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 MTD + atezolizumab
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: Atezolizumab
Atezolizumab will be given post IMA203 infusion, after hematologic recovery is achieved, for up to a year after IMA203 infusion.
Other Name: Tecentriq




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 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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 for the study
  • Measurable disease and accessible to biopsy
  • Adequate pulmonary function per protocol
  • Adequate organ and bone marrow function per protocol
  • Acceptable coagulation status per protocol
  • Adequate hepatic function per protocol
  • Adequate renal function per protocol
  • 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 or any of these rescue medications
  • 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, lymphodepletion, low-dose IL-2, and/or IMA203 treatment
  • 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
  • Concurrent participation in an interventional part of another clinical trial.

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.).


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
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Contact: Jorge Rivas, M.D., Ph.D. 346-204-5350 ctgovinquiries@immatics.com

Locations
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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 Regensburg, Franz-Josef-Strauß-Allee 11 Not yet recruiting
Regensburg, Bavaria, Germany, 93053
Contact: Daniel Heudobler, MD    +49 (0)941 944-14800    daniel.heudobler@ukr.de   
Principal Investigator: Daniel Heudobler, MD         
Universitätsklinikum Würzburg Recruiting
Würzburg, Bavaria, Germany, 97080
Contact       chatterjee_m@ukw.de   
Contact    +49 (0)931 201 40953      
Principal Investigator: Manik Chatterjee, MD         
Universitätsklinikum Bonn - Medizinische Klinik III Recruiting
Bonn, North Rhine-Westphalia, Germany, 53127
Contact    +49 (0)228 287-17233    tobias.holderried@ukbonn.de   
Contact    +49 (0)151 44048451      
Principal Investigator: Tobias Holderried, MD, PhD         
Universitätsklinikum C.-G.-Carus Dresden Recruiting
Dresden, Saxony, Germany, 01307
Contact    +49 (0)351 458 7566    Martin.Wermke@uniklinikum-dresden.de   
Principal Investigator: Martin Wermke, MD, PhD         
Universitätsklinikum Hamburg-Eppendorf Recruiting
Hamburg, Germany, 20246
Contact    +49 (0)40 7410 - 52960    c.bokemeyer@uke.de   
Contact    +49 (0)40 7410 - 53962      
Principal Investigator: Carsten Bokemeyer, MD, PhD         
Sponsors and Collaborators
Immatics US, Inc.
Investigators
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Study Director: Cedrik Britten, M.D. Immatics US, Inc.
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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: September 14, 2021
Last Verified: August 2021

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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
Additional relevant MeSH terms:
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Recurrence
Disease Attributes
Pathologic Processes
Atezolizumab
Antineoplastic Agents