Clinical trial NCT02992743: Letetresgene Autoleucel Engineered T Cells in NY-ESO-1 Positive Participants With Advanced Myxoid/ Round Cell Liposarcoma
Official title: A Pilot Study of NY-ESO-1c259T Cells in Subjects With Advanced Myxoid/ Round Cell Liposarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neoplasms
Keywords: Myxoid/ round cell liposarcoma
Letetresgene autoleucel
Immuno-oncology
T Cell Receptor
Leukapheresis
NY-ESO-1
Adoptive TCR T-cell therapy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2016-12-14
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial will evaluate safety and efficacy of Letetresgene autoleucel (GSK3377794) in participants with advanced myxoid/round cell liposarcoma or high-grade myxoid liposarcoma.

Detailed description: New York esophageal antigen-1 (NY-ESO-1) and LAGE-1a antigens are tumor-associated proteins that have been found in several tumor types. Clinical trials using adoptively transferred T-cells directed against NY-ESO-1/LAGE-1a have shown objective responses. Letetresgene autoleucel (GSK3377794) is the first generation of NY-ESO-1 specific T-cell receptor (TCR) engineered T-cells. This protocol investigates Letetresgene autoleucel treatment in Human Leukocyte Antigen (HLA)-A\*02+ participants with NY-ESO1+ advanced myxoid/round cell liposarcoma or high-grade myxoid liposarcoma.

Eligibility criteria: Inclusion Criteria:

* Participant is greater than equal to (\>=)18 years of age at the time of signing the study informed consent.
* Participant has a diagnosis of advanced (metastatic or inoperable) 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).
* Participant has measurable disease according to RECIST v1.1 criteria.
* Participant must have previously received or be intolerant to anthracycline based therapy for advanced (metastatic or inoperable) disease.
* Participants who received neoadjuvant/adjuvant anthracycline based therapy and progressed within 6 months of completion of therapy will be eligible.
* Participant 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) is positive for NY-ESO-1 expression by a designated central laboratory.
* Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
* Participant has a left ventricular ejection fraction \>=45%.
* Participant is fit for apheresis and has adequate venous access for the cell collection.
* Participants must satisfy pregnancy and contraceptive requirements per protocol and have adequate organ function per protocol specified values.

Exclusion Criteria:

* Any previous gene therapy using an integrating vector.
* Any previous allogeneic hematopoietic stem cell transplant.
* Participant has history of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study.
* Participant 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.
* Participant has known active brain or leptomeningeal metastases.
* Participant has other prior malignancy that is not in complete remission.
* Participant has uncontrolled intercurrent illness including, but not limited to:
* (i) Ongoing or active infection.
* (ii) Clinically significant cardiac disease
* (iii) Interstitial lung disease (participants with existing pneumonitis as a result of radiation are not excluded, however, participants must not be oxygen dependent).
* Participant has active infection with Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV), ), Hepatitis C virus (HCV) or human T-lymphotropic virus (HTLV).

Primary outcomes:
measure: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
timeFrame: Up to 24 months
measure: Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
timeFrame: Up to 24 months
Secondary outcomes:
measure: Time to Response (TTR) Assessed by Investigator
timeFrame: Up to 24 months
measure: Duration of Response (DOR) Assessed by Investigator
timeFrame: Up to 24 months
measure: Progression Free Survival (PFS) Assessed by Investigator
timeFrame: Up to 24 months
measure: Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer Assessment
timeFrame: Up to 24 months
measure: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer
timeFrame: Up to 24 months
measure: Time to Response (TTR) Assessed by Independent Reviewer
timeFrame: Up to 24 months
measure: Duration of Response (DOR) Assessed by Independent Reviewer
timeFrame: Up to 24 months
measure: Progression Free Survival (PFS) Assessed by Independent Reviewer
timeFrame: Up to 24 months
measure: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs
timeFrame: Up to 24 months
measure: Number of Participants With Adverse Event of Special Interest (AESI)
timeFrame: Up to 24 months
measure: Number of Participants With Any Grade Increase in Hematology Results at Worst-case Post-baseline
timeFrame: Up to 24 months
measure: Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline
timeFrame: Up to 24 months
measure: Number of Participants With Replication Competent Lentivirus (RCL)
timeFrame: Day 1 (pre-infusion), and at Week 12, Week 24, and 1 year post-infusion
measure: Number of Participants With Insertional Oncogenesis
timeFrame: Up to 2 years
measure: Number of Participants With Positive Anti-drug Antibodies (ADAs)
timeFrame: Up to 24 Months
measure: Maximum Transgene Expansion (Cmax) of GSK3377794
timeFrame: Day 2 to Day 15
measure: Time to Cmax (Tmax)
timeFrame: Day 2 to Day 15
measure: Area Under the Time Curve From Zero to Time 28 Days AUC(0-28) of GSK3377794
timeFrame: Up to 28 days
measure: Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval
timeFrame: Baseline, Day 1, Day 4 and Day 8
measure: Change From Baseline in ECG Mean Heart Rate
timeFrame: Baseline, Day 1 (Pre-dose), Day 4 and Day 8
Other outcomes:
Locations:
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Ann Arbor
country: United States
facility: GSK Investigational Site
state: Michigan
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: