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

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ClinicalTrials.gov Identifier: NCT03686124
Recruitment Status : Recruiting
First Posted : September 26, 2018
Last Update Posted : August 15, 2022
Sponsor:
Information provided by (Responsible Party):
Immatics US, Inc.

Study Description
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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 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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 102 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

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arms and Interventions
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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 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.


Outcome Measures
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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)


Eligibility Criteria
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Information from the National Library of Medicine

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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:

  • 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
  • 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.
  • 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
  • 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
  • Patients who have received more than 4 prior systemic treatment lines for treatment of advanced and/or metastatic disease.
  • Patients who are known to have at least one single tumor lesion that exceeds 10 cm in diameter
  • Any condition contraindicating leukapheresis, lymphodepletion, low-dose IL-2, and/or IMA203/IMA203CD8 treatment
  • Patients with active brain metastases
  • Concurrent participation in an interventional part of 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

Contacts and Locations
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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: Immatics US, Inc. +1 346 204-5400 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.
More Information
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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: August 15, 2022
Last Verified: August 2022

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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
Nivolumab
 Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action