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

• Status: Not yet recruiting
• Trial end date: 0000-00-00
• Target enrollment: 16
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Immatics US, Inc.
• Collaborator: M.D. Anderson Cancer Center
• Treatments: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Interleukin-2; Vidarabine
• Last Updated: 2017-08-21

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.