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TCR-engineered T Cells in NSCLC and HNSCC Patients (ACTengine) (ACTengine)

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ClinicalTrials.gov Identifier: NCT03247309
Recruitment Status : Recruiting
First Posted : August 11, 2017
Last Update Posted : September 27, 2017
Sponsor:
Collaborator:
M.D. Anderson Cancer Center
Information provided by (Responsible Party):
Immatics US, Inc.

Brief Summary:

This clinical research study investigates IMA201 which is composed of special immune cells (T cells, also called T lymphocytes) being genetically modified by introduction of a tumor-antigen specific T cell receptor (TCR) to fight against cancer. Patients that choose to take part in this study have advanced cancer where there is no (further) standard treatment for their cancer available OR current treatments are not tolerated.

The main purpose of this clinical research study is to confirm the safety of IMA201 and to define the highest safe dose of IMA201 cells to give to patients. The study will also investigate what the specific side effects of this treatment are, and to see whether this therapy shows clinical activity in patients with their advanced cancer.


Condition or disease Intervention/treatment Phase
Solid Tumor Cancer Head and Neck Squamous Cell Carcinoma Squamous Cell Non-small Cell Lung Cancer Biological: IMA201 T-Cells Diagnostic Test: IMA201_Detect Diagnostic Test: ACT-HLA Drug: Fludarabine Drug: Cyclophosphamide Biological: Recombinant human interleukin-2 Phase 1

Detailed Description:

SCREENING: First, the patient will have 2 sets of screening tests to determine eligibility: HLA (human leukocyte antigen) screening and Main screening. After both screenings are completed and if the patient is eligible, blood will be taken for the manufacture of IMA201.

The HLA screening test will be done by an investigational device. Patients must have the HLA-A*02:01 subtype to continue to the Main screening of the study. The Main screening will include medical tests and exams, including a tumor biopsy that will be tested for specific biomarkers by an investigational device called IMA201_Detect. Patients must be positive for at least one of the study's biomarkers to continue onto the leukapheresis part of the study.

Manufacturing phase: From the patient's blood collected at the leukapheresis, the investigators will make the IMA201 TCR-engineered T cells. In order to insert the new gene into the patient's T-cells, investigators will use a gene transfer technology. This will be done with a lentiviral vector derived from a virus. The vector was made specifically for this study and will carry the TCR genes into the T cells.

TREATMENT: In other clinical studies using T cells, some investigators found that giving chemotherapy before the T cell infusion can improve the amount of time the T cells stay in the body. Giving chemotherapy before a T cell infusion is called lymphodepletion. The chemotherapy used for lymphodepletion in this study will be a combination of cyclophosphamide and fludarabine which would be given in the days before the IMA201 T cell infusion. Two days after the last chemotherapy dose, the patient will be admitted to the hospital the night before the IMA201 infusion. The IMA201 treatment will be given at MD Anderson Cancer Center.

After IMA201 infusion, a low dose of IL-2 will be given twice daily for a period of time.

Since this study involves gene therapy, patients will be monitored throughout the study and for up to a total of 15 years.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Trial Evaluating Genetically Modified Autologous T Cells Expressing a T-Cell Receptor Recognizing a Cancer/Germline Antigen in Patients With Squamous Cell Non-small Cell Lung Cancer or Head and Neck Squamous Cell Carcinoma
Actual Study Start Date : September 26, 2017
Estimated Primary Completion Date : December 31, 2018
Estimated Study Completion Date : December 31, 2033

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: IMA201 T-Cells
  • Pre-conditioning by non-myeloablative chemotherapy with Fludarabine and Cyclophosphamide
  • One dose of IMA201 will be infused intravenously. Four dose levels will be evaluated. At least two patients per cohort will be treated.
  • Post-infusion of IMA201, administration of low-dose recombinant human interleukin-2
Biological: IMA201 T-Cells
The cell dose will be based on viable CD3+CD8+ HLA-Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula.
Diagnostic Test: IMA201_Detect
IMA201_Detect 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 clinical trials with investigational IMA201 T-Cell therapy. IMA201_Detect is intended for investigational use only.
Diagnostic Test: ACT-HLA
An assay used to determine whether a patient is positive for the allele HLA-A*02:01 or not, and thus is eligible for treatment with an ACTengine adoptive T-cell product.
Drug: Fludarabine
Fludarabine infusion
Other Name: Fludarabine Monophosphate
Drug: Cyclophosphamide
Cyclophosphamide infusion
Other Name: Cytoxan
Biological: Recombinant human interleukin-2
Low dose IL-2 Infusion for two weeks
Other Names:
  • Aldesleukin
  • Proleukin



Primary Outcome Measures :
  1. Incidence of adverse events (AE) [ Time Frame: up to 15 years post-treatment ]
    During treatment and treatment observation phases and long term gene safety follow up, AE and SAE will be captured per CTCAE v4.0. AEs and SAEs will be summarized.


Secondary Outcome Measures :
  1. Duration of infused T cells over time (Persistence of T cells) [ Time Frame: Up to 12 months ]
    Blood samples will be collected at selected time points (pre- and post-IMA201 treatment at set time points) to assess the persistence of IMA201 T-cells in the blood.

  2. Incidence of infused T cells (Functionality of T cells) [ Time Frame: Up to 12 months ]
  3. Success Rates of T cell generation (Feasibility of ACTengine approach) [ Time Frame: This endpoint can be evaluated after production of the last patient's specific T-cell product, i.e. after release of the last patient's cell product. Approximately 10 months ]
  4. Number of subjects with Clinical response [ Time Frame: 12 weeks and 24 weeks post IMA201 infusion ]
  5. Levels of Blood biomarkers [ Time Frame: until the end of the trial, up to 15 years from last patient treatment ]
  6. Levels of Tumor biomarkers [ Time Frame: until the end of the trial, up to 15 years from last patient treatment ]
  7. Rate of successful biomarker tests for tumor samples collected [ Time Frame: This can be evaluated after last patient's enrollment, approximately 12 months ]
  8. Percentages of patients expressing individual targets [ Time Frame: This can be evaluated after last patient's enrollment, approximately 10 months after start of trial. ]
  9. Concordance of HLA-A*02:01 Determination assay [ Time Frame: This can be evaluated after last patient's enrollment, approximately 10 months after start of trial. ]

Other Outcome Measures:
  1. Overall Survival (OS) will be assessed. [ Time Frame: until the end of the trial, up to 15 years from last patient treatment. ]
  2. Progression Free Survival (PFS) will be assessed. [ Time Frame: until the end of the trial, up to 15 years from last patient treatment. ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

HLA SCREENING Inclusion:

  • Signed a written informed consent form.
  • Pathologically confirmed diagnosis of stage IIIB/IV recurrent squamous cell NSCLC who has received systemic therapy. OR Pathologically confirmed diagnosis of stage III/IV recurrent or metastatic HNSCC (oral cavity, pharynx, larynx) who had received systemic therapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
  • Women of childbearing potential must use adequate contraception (hormonal or barrier method of birth control; abstinence).

MAIN SCREENING INCLUSION

  • Signed a written informed consent form.
  • Pathologically confirmed diagnosis of stage IIIB/IV recurrent squamous cell NSCLC defined as not amenable to local curative therapy (surgery, radiation, or chemoradiation), and refractory to systemic therapy, including previous treatment as defined per protocol.

OR

  • Pathologically confirmed diagnosis of stage III/IV recurrent or metastatic HNSCC (oral cavity, pharynx, larynx) not amenable to local therapy with curative intent (surgery, radiation therapy, or chemoradiation) including previous treatment defined per protocol.
  • HLA phenotype HLA-A*02:01.
  • Patient's tumor must express specified biomarkers
  • ECOG performance status 0-1.
  • Normal organ and marrow function, defined per protocol
  • Measurable disease
  • At least one lesion (metastasis or primary tumor) being considered accessible for a biopsy.
  • Adequate hepatic function, as defined per protocol
  • Serum creatinine within 1.5 x normal range for age OR creatinine clearance with a recommended GFR ≥ 50 mL/min/1.73m2.
  • Adequate pulmonary function, defined per protocol and oxygen saturation >92% on room air.
  • Acceptable coagulation status: INR ≤1.5 x ULN and PTT ≤1.5 x ULN.
  • Women of childbearing potential must use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry until 6 months after the infusion of IMA201.
  • Male patients must agree to use effective contraception or abstinence while on study and for 90 days after the infusion of IMA201.
  • Confirmed availability of production capacities for the patient's ACTengine IMA201 product prior to the leukapheresis.

TREATMENT INCLUSION:

  • Signed informed consent form
  • Available IMA201 T-cell product that was produced for the patient and passed all release tests.
  • ECOG performance status 0-1.
  • Adequate hepatic function per protocol.
  • Serum creatinine within 1.5 x normal range for age or creatinine clearance with a recommended GFR ≥ 50 mL/min/1.73m2.
  • Measurable disease.
  • Women of childbearing potential must use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry until 6 months after the infusion of IMA201.
  • Male patients must agree to use effective contraception or be abstinent while on study and for 90 days after the infusion of IMA201.

Exclusion Criteria:

HLA EXCLUSION:

  • History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 3 years.
  • Pregnant or is breastfeeding.
  • Serious autoimmune disease

MAIN SCREENING EXCLUSION:

  • Any condition contraindicating leukapheresis.
  • Brain metastases.
  • HIV infection, active Hepatitis B or C infection
  • Concomitant therapy indicated with any of the following: interferons or other non-study immunotherapy regimens; immunosuppressive agents; other investigational therapies; or chronic use of systemic corticosteroids.
  • Severe immune-related toxicity related to checkpoint inhibitors defined as any Grade 4 toxicity or Grade 3 toxicity requiring corticosteroid treatment for longer than 12 weeks.
  • Cardiac conditions per protocol
  • Prior stem cell transplantation or solid organ transplantation.
  • Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study
  • Active diverticulitis, intra-abdominal abscess or gastrointestinal (GI) obstruction.
  • History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 3 years.
  • Pregnant or is breastfeeding.
  • Serious autoimmune disease
  • History of hypersensitivity to cyclophosphamide, fludarabine or IL-2.
  • History of or current immunodeficiency disease or prior treatment compromising immune function
  • Patients with active pneumonitis.

TREATMENT EXCLUSION

  • Received chemotherapy, surgery, or radiotherapy (for therapeutic purposes) within 3 weeks (4 weeks for monoclonal antibodies or investigational drugs, 1 week for tyrosine kinase inhibitor (TKI) (e.g. erlotinib, gefitinib) or the patient has not recovered (from grade ≥2 side effects of the previous therapy) prior to lymphodepletion regimen.
  • Pregnant or breastfeeding.
  • Active pneumonitis.
  • Patient unable to tolerate lymphodepletion, low-dose IL-2 and/or ACTengine IMA201 treatment.
  • Severe immune-related toxicity related to checkpoint inhibitors defined as any Grade 4 toxicity or Grade 3 toxicity requiring corticosteroid treatment for longer than 12 weeks.

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): NCT03247309


Contacts
Contact: Hong Ma, M.D. 346-204-5350 ma@immatics.com
Contact: George R Blumenschein, Jr., M.D. gblumens@mdanderson.org

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Immatics US, Inc.
M.D. Anderson Cancer Center
Investigators
Study Director: Hong Ma, M.D. Immatics US, Inc.
Principal Investigator: George R Blumenschein, Jr., M.D. MDACC

Responsible Party: Immatics US, Inc.
ClinicalTrials.gov Identifier: NCT03247309     History of Changes
Other Study ID Numbers: IMA201-101
First Posted: August 11, 2017    Key Record Dates
Last Update Posted: September 27, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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
Pediatric Postmarket Surveillance of a Device Product: No

Keywords provided by Immatics US, Inc.:
T-cell therapy
immunotherapy
HLA-A*02:01
adoptive cellular therapy
T-Cell Receptor

Additional relevant MeSH terms:
Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplasms, Squamous Cell
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Aldesleukin
Interleukin-2
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents