Clinical Trial 18782

Cancer Type: Sarcoma
Interventions:NY-ESO-1c259T; cyclophosphamide; cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

Study Type: Treatment
Phase of Study: Pilot
Investigators:

  • Mihaela Druta

Overview

Study Title

A Pilot Study Of NY-ESO-1c259T Cells In Subjects With Advanced Myxoid/ Round Cell Liposarcoma

Summary

The purpose of this clinical research study is to answer the following questions: How safe is the investigational drug and what are the side effects that might be related to it? Can the investigational drug help participants with myxoid round cell liposarcoma? How does the participant's tumor affect how investigational drug works?

Objective

Primary: To evaluate the efficacy of autologous genetically modified T cells (NY-ESO-1c259T) in HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 subjects with NY-ESO-1 expressing advanced myxoid/ round cell liposarcoma. Secondary: To evaluate the efficacy of autologous genetically modified T cells (NY-ESO-1c259T) in HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 subjects with NY-ESO-1 expressing advanced myxoid/ round cell liposarcoma. To evaluate the safety and tolerability of autologous genetically modified T cells (NY-ESO-1c259T) in HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 subjects with NY-ESO-1 expressing advanced myxoid/ round cell liposarcoma To develop and validate for regulatory approval and registration a NY-ESO-1. companion diagnostic assay which will be used in the future to aid in determining whether subjects with myxoid/ round cell liposarcoma whose tumors express NY-ESO-1 will benefit from treatment with NY ESO 1c259T.

Inclusion Criteria

  • Participant (or legally authorized representative) has voluntarily agreed to participate by giving written informed consent in accordance with ICH GCP guidelines and applicable local regulations.
  • Has agreed to abide by all protocol required procedures including study related assessments, and management by the treating institution for the duration of the study and long term follow-up.
  • Participant is ≥18 years of age at the time of signing the study informed consent.
  • Has a diagnosis of high grade myxoid liposarcoma / myxoid round cell liposarcoma confirmed histologically and by the presence of the reciprocal chromosomal translocation t(12;16)(q13;p11) or t(12; 22) (q13;q12)
  • Has advanced (metastatic or inoperable) high grade myxoid liposarcoma / myxoid round cell liposarcoma. Inoperable refers to a tumor lesion in which clear margins cannot be obtained without leading to significant functional compromise
  • Has measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
  • Must be HLA A*02:01, HLA A*02:05 and/or HLA-A*02:06 positive.
  • Participant's tumor (either the most recent archival specimen or a fresh biopsy) shows positive NY-ESO-1 expression defined as ≥30% of cells that are 2+ or 3+ by immunohistochemistry. All samples must have been pathologically reviewed by an Adaptimmune designated central laboratory.
  • Must have previously received or be intolerant to anthracycline based therapy for advanced (metastatic or inoperable) disease. Patients who received neoadjuvant/adjuvant anthracycline based therapy and progressed within 6 months of completion of therapy will be eligible.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
  • Has a left ventricular ejection fraction ≥45%.
  • Is fit for apheresis and has adequate venous access for the cell collection.
  • Female participants of childbearing potential (FCBP) must have a negative urine or serum pregnancy test AND must agree to use effective contraception throughout the study, starting at the first dose of chemotherapy for at least 12 months thereafter and 4 months after the gene modified cells are no longer detected in the blood, whichever is longer. Or, Males participants must be surgically sterile or agree to use effective contraception starting at the first dose of chemotherapy and for 4 months thereafter (if indicated in the country specific monograph/label for cyclophosphamide).
  • Must have adequate organ function.

  • Exclusion Criteria

  • Has received or plans to receive the following therapy/treatment within the following periods prior to leukapheresis or lymphodepleting chemotherapy: Cytotoxic chemotherapy within 4 weeks; Immune therapy (monoclonal antibody therapy, checkpoint inhibitors) within 4 weeks; Use of an anti-cancer vaccine within 2 months in the absence of tumor response, or the patient should be excluded if their disease is responding to an experimental vaccine given within 6 months; Any previous gene therapy using an integrating vector; Corticosteroids or any other immunosuppressive therapy within 2 weeks; Use of inhaled or topical cutaneous steroids is permitted; Any previous allogeneic hematopoietic stem cell transplant; Investigational treatment or clinical trial within 4 weeks.
  • Radiotherapy to the target lesions within 3 months prior lymphodepleting chemotherapy. A lesion with unequivocal progression may be considered a target lesion. There is no washout period for palliative radiation to non-target lesions.
  • Potential participant that has toxicity from previous anti-cancer therapy must have recovered to ≤ Grade 1 (except for non-clinically significant toxicities, e.g., alopecia, vitiligo). Patients with Grade 2 toxicities that are deemed stable or irreversible (e.g. peripheral neuropathy) can be enrolled.
  • Has history of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study.
  • Has history of chronic or recurrent (within the last year prior to screening) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments.
  • Has known active brain or leptomeningeal metastases. Patients with prior history of brain metastasis who have undergone local therapy (i.e., metastatectomy and/or radiation) and show no evidence of local recurrence or progression over the past 3 months prior to screening are eligible.
  • Has other prior malignancy that is not in complete remission.
  • Has electrocardiogram (ECG) showing clinically significant abnormality at screening or an average QTc interval (Fridercia's or Bazett's formula) >450 msec in males and >470 msec in females (>480 msec for patients with Bundle Branch Block (BBB)).
  • Has 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 (NYHA) Class 3 or Class 4; Uncontrolled clinically significant arrhythmia in last 6 months; Acute Coronary Syndrome (ACS) (angina or MI) in last 6 months; Interstitial lung disease (potential participants with existing pneumonitis as a result of radiation are not excluded, however, participants must not be oxygen dependent).
  • Potential participants who in the opinion of the Investigator will be unlikely to fully comply with protocol requirements.
  • An active infection with HIV, HBV, HCV or HTLV
  • Pregnant or breastfeeding.