Letetresgene Autoleucel Engineered T Cells in NY-ESO -1 Positive Advanced Non-Small Cell Lung Cancer (NSCLC)

NCT ID: NCT02588612

Last Updated: 2021-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-01
• Study Completion Date: 2020-08-10

Brief Summary

This trial will evaluate safety and efficacy of letetresgene autoleucel (GSK3377794) in participants with metastatic NSCLC.

Detailed Description

New York esophageal antigen-1 (NY-ESO-1) and L antigen family member (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 engineered TCR T-cells. This protocol investigates letetresgene autoleucel treatment in Human Leukocyte Antigen (HLA)*-A*02+ participants with NY-ESO1+ advanced metastatic non-small cell lung cancer as second line treatment.

Conditions

Neoplasms

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

letetresgene autoleucel (GSK3377794)

Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive letetresgene autoleucel (GSK3377794), as a single intravenous (IV) infusion after completing lymphodepleting chemotherapy.

Group Type: EXPERIMENTAL

letetresgene autoleucel (GSK3377794)

Intervention Type: DRUG

letetresgene autoleucel (GSK3377794) as an IV infusion.

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide will be used as a lymphodepleting chemotherapy.

Fludarabine

Intervention Type: DRUG

Fludarabine will be used as a lymphodepleting chemotherapy.

Interventions

letetresgene autoleucel (GSK3377794)

letetresgene autoleucel (GSK3377794) as an IV infusion.

Intervention Type: DRUG

Cyclophosphamide

Cyclophosphamide will be used as a lymphodepleting chemotherapy.

Intervention Type: DRUG

Fludarabine

Fludarabine will be used as a lymphodepleting chemotherapy.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participant is >=18 years of age on the day of signing informed consent.
• Participant has a diagnosis of histologically or cytologically confirmed advanced non-small cell lung cancer (Stage IIIB or IV) or recurrent disease.
• Participants with known epidermal growth factor receptor (EGFR) mutations or Anaplastic lymphoma kinase receptor (ALK) or ROS1 gene rearrangements must have failed (disease progression [PD] or unacceptable toxicity) prior EGFR or ALK or ROS1 tyrosine kinase inhibitor, respectively (PD or unacceptable toxicity). There is no limit to lines of prior anti-cancer therapy.
• Participant has measurable disease according RECIST v1.1 criteria.
• Participant is HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive.
• Participant's tumor is positive for NYESO and/or LAGE-1a expression by a designated central laboratory.
• Participant has Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
• Participant has an anticipated life expectancy >3 months.
• Participant has left ventricular ejection fraction >=50 percent(%).
• Participant is fit for leukapheresis and has adequate venous access for the cell collection.
• Male or Female. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Participant must have adequate organ function.

Exclusion Criteria

• Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per Investigator assessment).
• Washout periods for prior radiotherapy and chemotherapy and other systemic therapy must be followed.
• 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.
• Toxicity from previous anti-cancer therapy that has not recovered to less than or equal to (<=)Grade 1 prior to enrollment (with exceptions).
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, fludarabine, or other agents used in the study.
• Central nervous system (CNS) metastases.
• Active brain metastases or leptomeningeal metastases.
• 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.
• Other active malignancies besides NSCLC within 3 years prior to Screening not in complete remission.
• Unintended weight loss >10% in 6 months preceding study entry.
• Corrected QT interval (QTc) >450 milliseconds (msec) or QTc >480 msec for participants with Bundle Branch Block (BBB).
• Uncontrolled intercurrent illness.
• Participants who in the opinion of the Investigator will be unlikely to fully comply with protocol requirements.
• Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) or human T-cell lymphotropic virus (HTLV).
• Participant is pregnant or breastfeeding.
• Major surgery within 4 weeks prior to lymphodepleting chemotherapy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Tampa, Florida, United States

GSK Investigational Site

Houston, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ADP-0011-004

Identifier Type: OTHER

Identifier Source: secondary_id

2016-002517-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

208749

Identifier Type: -

Identifier Source: org_study_id