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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 1

Conditions: Neoplasms

Treatments: Drug: Fludarabine; Drug: letetresgene autoleucel (GSK3377794); Drug: Cyclophosphamide

Study type: Interventional

Funder types: Industry

Identifiers

NCT02588612

ADP-0011-004 (Other Identifier)

2016-002517-21 (EudraCT Number)

208749

Details and patient eligibility

About

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

Full 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.

Enrollment: 10 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

letetresgene autoleucel (GSK3377794)

Experimental group

Description:

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.

Treatment:

Drug: Fludarabine

Drug: letetresgene autoleucel (GSK3377794)

Drug: Cyclophosphamide