Study to assess the safety and efficacy of T cell therapy in patients with advanced cancer

Phase 1

• Conditions: Synovial sarcoma, Myxoid round cell liposarcoma; MedDRA version: 20.0Level: PTClassification code 10075333Term: Soft tissue sarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-000589-39-GB
• Lead Sponsor: Adaptimmune LLC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-08-06
• Last Update Posted: 10 August 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

1. Subject (or legally authorized representative) voluntarily agrees to participate by giving written Informed Consent
(and Assent as applicable)in accordance with ICH GCP guidelines and applicable local regulations.
2. Subject (or legally authorized representative) agrees to abide by all protocol required procedures including study
related assessments and management by the treating institution for the duration of the study, including long term
follow-up.
3. Age =16 and <75 years at the time the Pre-screening informed consent/assent is signed.
4. Diagnosis of advanced (metastatic or inoperable) synovial sarcoma or myxoid liposarcoma / myxoid round cell
liposarcoma confirmed by cytogenetics. Inoperable refers to a tumor lesion in which clear surgical excision margins
cannot be obtained without leading to significant functional compromise.
a. For Synovial Sarcoma: confirmation by the presence of a translocation between SYT on the X chromosome and
SSX1, SSX2 or, SSX4 on chromosome 18 (may be presented in the pathology report as t (X; 18)).
b. For MRCLS: confirmation by the presence of the reciprocal chromosomal translocation t(12;16)(q13;p11) or t(12; 22)
(q13;q12)
5. Must have previously received either an anthracycline or ifosfamide containing regimen. Subjects who are intolerant
to both anthracycline and ifosfamide must have previously received at least one systemic therapy.
6. Measurable disease according to RECIST v1.1.
7. Positive for HLA-A*02:01, HLA-A*02:03, HLA-A*02:06 allele via Adaptimmune designated central laboratory testing. HLA-A*02 alleles having the same protein sequence as these alleles in the peptide binding domains (P group) will also be included. Other HLA-A*02 alleles may be eligible after adjudication with the sponsor.
8. Tumor (either an archival specimen or a fresh biopsy) shows MAGE-A4 expression of =2+ staining in =30% of the
cells by immunohistochemistry. All samples must have been pathologically reviewed by an Adaptimmune designated
central laboratory confirming expression.
9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
10. Left ventricular ejection fraction (LVEF) =50%.
11. Fit for leukapheresis and adequate venous access can be established for the
cell collection.
12. Female subjects of childbearing potential (FCBP) must have a negative urine or serum pregnancy test AND mustagree to use an effective method of contraception starting at the first dose of chemotherapy and continuing for at least
12 months, or 4 months after the gene modified cells are no longer detected in the blood, whichever is longer.
- OR
Male subjects must be surgically sterile or agree to use a double barrier contraception method or abstain from
heterosexual activity with a FCBP starting at the first dose of chemotherapy and continuing for 4 months thereafter (or
longer if indicated in the country specific monograph/label for cyclophosphamide).
13. Must have adequate organ function as indicated by the laboratory values in
a table from the protocol. Please see protocol page 20
Are the trial subjects under 18? yes
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 27
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

1. Positive for HLA-A*02:05 in either allele via Adaptimmune designated central laboratory testing. HLA-A*02 alleles having the same protein sequence as HLA-A*02:05 in the peptide binding domain (P groups) will also be excluded. Other alleles may be exclusionary after adjudication with the sponsor.
2. Received or plans to receive therapy/treatment prior to leukaphereseisis or lymphodepleting chemotherapy
3. Toxicity from previous anti-cancer therapy must have recovered to = Grade 1 prior to enrollment (except for nonclinically
significant toxicities, e.g., alopecia, vitiligo). Subjects with Grade 2 toxicities that are deemed stable or
irreversible (e.g. peripheral neuropathy) can be enrolled.
4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine,
cyclophosphamide or other agents used in the study.
5. History of autoimmune or immune mediated disease. Subjects with hypothyroidism, diabetes, adrenal insufficiency
or pituitary insufficiency that are stable on replacement therapy are eligible. Subjects with disorders such as asthma,
psoriasis or atopic dermatitis that are well controlled without requiring systemic immunosuppression are also
eligible.
6. Leptomeningeal disease, carcinomatous meningitis or symptomatic CNS metastases. Subjects with a prior
history of symptomatic CNS metastases must have received treatment (i.e., stereotactic radiosurgery (SRS), whole
brain radiation (WBRT) or surgery) and be neurologically stable for at least 1 month, not requiring anti-seizure
medications and off of steroids for at least 14 days prior to leukapheresis and lymphodepletion. Antiseizure
prophylaxis is permitted. Subjects who have
asymptomatic CNS metastases without associated edema, shift, requirement for steroids
or anti-seizure medications for the treatment of seizures are eligible.
7. Any other prior malignancy that is not in complete remission. Resectable
squamous or basal cell carcinoma of the skin is acceptable. Prior malignancies that have been surgically resected
and show no evidence of disease are acceptable.
8. 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;
Acute Coronary Syndrome (ACS) (angina or MI) in last 6 months;
• Interstitial lung disease (subjects with existing pneumonitis as a result of radiation are not excluded, however,
subjects must not be oxygen dependent);
• Congenital or family history of long QT syndrome;
• Current uncontrolled hypertension despite optimal medical therapy;
• History of stroke or central nervous system bleeding; transient ischemic attack (TIA) or reversible ischemic
neurologic deficit (RIND) in last 6 months;
9. Active infection with HIV, HBV, HCV or HTLV as defined below:
• Positive serology for HIV;
• Active hepatitis B infection as demonstrated by test for hepatitis B surface antigen. Subjects who are hepatitis B
surface antigen negative but are hepatitis B core antibody positive must have undetectable hepatitis B DNA and
receive prophylaxis against viral reactivation. Prophylaxis should be initiated prior to lymphodepleting therapy and
continued for 6 months;
Active hepatitis C infection as demonstrated by hepatitis C RNA test. Subjects who are HCV antibody positive will be
screened for HCV RNA by any RT PCR or

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified