Clinical Trial 18522

Cancer Type: Thoracic
Interventions:MAGE-A10c796T

Study Type: Treatment
Phase of Study: Phase I/II
Investigators:

  • Benjamin Creelan

Overview

Study Title

A Phase I Dose Escalation Open Label Clinical Trial Evaluating the Safety and Efficacy of MAGE-A10c796T in Subjects with Stage IIIb or Stage IV Non-Small Cell Lung Cancer (NSCLC)

Summary

The purpose of this study is to test the safety of genetically changed T cells, an investigational therapy, and find out what effects, if any, they have in participants with lung cancer. T cells are a natural type of immune cell in the blood that can be changed in a laboratory with the aim to destroy some types of cancer cells. The changed T cells used in this study will be the participant¿s own T cells that have been genetically changed with the aim of attacking and destroying cancer cells.

Objective

Primary: To evaluate the safety and tolerability of MAGE-A10c796T autologous genetically modified T cells in HLA-A*0201 and HLA-A*0206 positive subjects with MAGE- A10 positive advanced NSCLC. Secondary: 1- To evaluate the efficacy of MAGE-A10c796T. 2- To measure persistence of genetically modified cells in the body. 3- To evaluate the phenotype and functionality of genetically modified cells isolated from peripheral blood or tumor post infusion. 4- To evaluate MAGE-A10 expression in tumor tissue, before and after treatment, and correlate with clinical response to treatment.

Inclusion Criteria

  • Has voluntarily agreed to participate by giving written informed consent
  • Age 18 years or older
  • Histologically or cytologically confirmed diagnosis of advanced non-small cell lung cancer (stage IIIB or IV) or recurrent disease.
  • Has failed at least one platinum-containing regimen and have disease progression or have persistent, measurable disease following 4 - 6 cycles of chemotherapy. Potential participants with known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase receptor (ALK) or ROS1 gene rearrangements must have failed (progressive disease or unacceptable toxicity) prior EGFR or ALK or ROS1 tyrosine kinase inhibitor, respectively. May have received PD-1 or PDL-1 inhibitors. There is no limit on lines of prior anti-cancer therapy.
  • Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  • Must be HLA-A*0201 or HLA-A*0206 positive
  • Participant's tumor (either an archival specimen or a fresh biopsy if archival tissue is unavailable) has been pathologically reviewed by a designated central laboratory confirming MAGE-A10 expression.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 and anticipated life expectancy >3 months. Potential participants with a history of chronic or recurrent (within the last year prior to enrollment) severe autoimmune or active immune-mediated disease requiring steroids or other immunosuppressive treatments are NOT eligible
  • Must have normal left ventricular ejection fraction ≥50%
  • Females of childbearing potential (FPCP) must have a negative urine or serum pregnancy test. FPCP must agree to use maximally effective birth control or to abstain from heterosexual activity throughout the study, starting at the first dose of chemotherapy through 18 months after the infusion of cells and until persistence of gene modified cells are not found in the blood. Effective contraceptive methods include intra-uterine device, oral or injectable hormonal contraception, or 2 adequate barrier methods. Spermicides alone are not an adequate method of contraception. Or Male participants must be surgically sterile or agree to use a double barrier contraception method upon enrolment starting at the first dose of chemotherapy through at least 4 months after treatment.
  • Must have adequate organ function
  • Prior to cytoreductive chemotherapy, all participants must have failed at least one prior platinum-containing regimen and have disease progression or have persistent, measurable disease following 4 - 6 cycles of chemotherapy.

  • Exclusion Criteria

  • Cytotoxic chemotherapy within 3 weeks prior to leukapheresis; Immune therapy (including monoclonal antibody therapy, checkpoint inhibitors) or biological therapy within 4 weeks prior to leukapheresis; Corticosteroids or any other immunosuppressive therapy within 2 weeks prior to leukapheresis (NOTE: recent or current use of inhaled or topical steroids is not exclusionary); Tyrosine kinase inhibitors (e.g. erlotinib, gefitinib) and any other anti-cancer treatment within 1 week prior to leukapheresis; Investigational treatment within 4 weeks prior to leukapheresis; Experimental anti-cancer vaccine within 2 months prior to leukapheresis in the absence of response or in the opinion of the Investigator is responding to an experimental vaccine given within 6 months prior to leukapheresis; Any prior gene therapy using an integrating vector.
  • Is HLA-A*02:05, HLA-B*15:01 and/or HLA-B*46:01 positive.
  • Toxicity from previous anti-cancer therapy that has not recovered to Grade less than or equal to 1 prior to enrollment (except for non-clinically significant toxicities, e.g., alopecia, vitiligo). Patients with existing pneumonitis as a result of radiation are not excluded; however, cannot be oxygen dependent. Those with Grade 2 toxicities that are deemed stable or irreversible (e.g., peripheral neuropathy) can be enrolled on a case-by-case basis with prior consultation and agreement with the Sponsor Study Physician.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, fludarabine or other agents used in the study.
  • History of chronic or recurrent (within the last year prior to enrollment) severe autoimmune or active immune-mediated disease requiring steroids or other immunosuppressive treatments
  • Has active brain or leptomeningeal metastases. Potential participants with prior history of brain metastasis who have undergone local therapy (i.e., metastasectomy and/or radiation) and show no evidence of local recurrence or progression over the past 3 months prior to screening are eligible.
  • Other active malignancy besides NSCLC within 3 years prior to screening. Exceptions: adequately treated malignancies not likely to require therapy (e.g., completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma). Must be in complete remission from prior malignancy in order to be eligible to enter the study.
  • Unintended weight loss >10% in 6 months preceding study entry
  • Electrocardiogram (ECG) showing clinically significant abnormality at Screening or showing an average QTc interval ≥450 msec in males and ≥470 msec in females (≥480 msec for subjects with Bundle Branch Block over 3 consecutive ECGs).
  • Uncontrolled intercurrent illness including, but not limited to: Ongoing or active infection; Clinically significant cardiac disease defined by congestive heart failure New York Heart Association Class >1; uncontrolled clinically significant arrhythmia in last 6 months; acute coronary syndrome (angina or myocardial infarction) in last 6 months; Inadequate pulmonary function with mechanical parameters > Active infection with HIV, HBV or HTLV
  • Pregnant or breastfeeding
  • Additional criteria may apply