Phase 2 N=23 Treatment

Letetresgene Autoleucel Engineered T Cells in NY-ESO-1 Positive Participants With Advanced Myxoid/ Round Cell Liposarcoma

Neoplasms

Bottom Line

View on ClinicalTrials.gov: NCT02992743 ↗

Enrolled (actual)

Serious AEs

52.2%

Results posted

Nov 2022

Primary outcome: Primary: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment — 20; 40 Percentage of participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: letetresgene autoleucel (GSK3377794) (Drug); Cyclophosphamide (Drug); Fludarabine (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: GlaxoSmithKline
Primary completion: Nov 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment	20; 40	—
PRIMARY Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment	0; 0; 2; 4; 8; 5	—
SECONDARY Time to Response (TTR) Assessed by Investigator	1.856; 1.938	—
SECONDARY Duration of Response (DOR) Assessed by Investigator	5.31; 7.47	—
SECONDARY Progression Free Survival (PFS) Assessed by Investigator	5.36; 8.74	—
SECONDARY Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer Assessment	0; 0; 2; 4; 8; 3	—
SECONDARY Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer	20; 40	—
SECONDARY Time to Response (TTR) Assessed by Independent Reviewer	2.366; 1.889	—
SECONDARY Duration of Response (DOR) Assessed by Independent Reviewer	NA; 7.16	—
SECONDARY Progression Free Survival (PFS) Assessed by Independent Reviewer	4.67; 9.03	—
SECONDARY Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	5; 7; 13; 10	—
SECONDARY Number of Participants With Adverse Event of Special Interest (AESI)	10; 10; 6; 10; 10; 10	—
SECONDARY Number of Participants With Any Grade Increase in Hematology Results at Worst-case Post-baseline	9; 10; 10; 10; 10; 10	—
SECONDARY Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline	5; 8; 1; 4; 9; 9	—
SECONDARY Number of Participants With Replication Competent Lentivirus (RCL)	0; 0	—
SECONDARY Number of Participants With Insertional Oncogenesis	0; 0	—
SECONDARY Number of Participants With Positive Anti-drug Antibodies (ADAs)	0; 0	—
SECONDARY Maximum Transgene Expansion (Cmax) of GSK3377794	66991.71; 108485.91	—
SECONDARY Time to Cmax (Tmax)	2; 4	—
SECONDARY Area Under the Time Curve From Zero to Time 28 Days AUC(0-28) of GSK3377794	727135.6; 1142798.27	—
SECONDARY Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval	152.9; 142; -2.3; -2.2; -10.7; -4	—
SECONDARY Change From Baseline in ECG Mean Heart Rate	73.0; 78.0; 1.6; 4.8; 20.1; 38.9	—

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.

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).

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02992743). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.