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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Cancer; Solid Tumor, Adult; Refractory Cancer; Recurrent Cancer
• Intervention / Treatment: Biological: IMA203 Product; Device: IMADetect®; Drug: nivolumab (Opdivo®); Biological: IMA203CD8 Product

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.

• Study Type: Interventional
• Enrollment (Estimated): 186
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Immatics US, Inc.; Phone Number: +1 346 204-5400; Email: ctgovinquiries@immatics.com

Study Locations

• Germany
  • Berlin, Germany, 12203
    • Recruiting
    • Charité Benjamin Franklin - Klinik für Hämatologie und Onkologie
  • Hamburg, Germany, 20246
    • Recruiting
    • Universitätsklinikum Hamburg-Eppendorf
  • Bavaria
    • Würzburg, Bavaria, Germany, 97080
      • Recruiting
      • Universitätsklinikum Würzburg
  • North Rhine-Westphalia
    • Bonn, North Rhine-Westphalia, Germany, 53127
      • Recruiting
      • Universitätsklinikum Bonn - Medizinische Klinik III
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Recruiting
      • Universitätsklinikum C.-G.-Carus Dresden
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami Hospital and Clinics
      • Contact: Phone Number: 305-243-2647; Email: CRSCutaneous@miami.edu
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
      • Contact: Phone Number: 212-342-5162; Email: cancerclinicaltrials@cumc.columbia.edu
      • Principal Investigator: Ran Reshef, MD
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • University of Pittsburgh Medical Center
      • Contact: Jason Luke, M.D.; Phone Number: 412-623-6132; Email: lukejj@upmc.edu
      • Principal Investigator: Jason Luke, M.D.
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas MD Anderson Cancer Center
      • Contact: Dejka M Araujo, M.D.; Phone Number: 713-792-3626; Email: daraujo@mdanderson.org
      • Principal Investigator: Dejka M Araujo, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	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.; 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.
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: Dose Escalation B; Dose escalation of IMA203CD8	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.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate safety and tolerability of treatment with treatment with ACTengine® IMA203/IMA203CD8 products as monotherapy or in combination with nivolumab	Treatment emergent adverse events	35 days
Determine the MTD and/or recommended dose for extension for IMA203/IMA203CD8	Number of patients with dose-limiting toxicities (DLTs)	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistence of T-cells	Measurement of TCR-engineered T cells in peripheral blood	up to 5 years post treatment
Tumor response	Response Evaluation Criteria In Solid Tumors (RECIST) 1.1	up to 12 months
Tumor response	Immune-Related Response Evaluation Criteria In Solid Tumors (irRECIST)	up to 12 months

Collaborators and Investigators

• Sponsor: Immatics US, Inc.
• Investigators: Study Director: Cedrik Britten, M.D., Immatics US, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2019
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: September 25, 2018
• First Submitted That Met QC Criteria: September 25, 2018
• First Posted (Actual): September 26, 2018

Study Record Updates

• Last Update Posted (Actual): October 25, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: immunotherapy; Ovarian Carcinoma; T-cell therapy; Melanoma (Skin); Melanoma, Uveal; Uterine Carcinoma; Uterine Carcinosarcoma; Immatics
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: IMA203-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes