Pilot Immunotherapy Study With Letetresgene Autoleucel (Lete-cel, GSK3377794)T-cells Specific in NY-ESO-1/ LAGE-1a-positive Advanced Non-small Cell Lung Cancer (NSCLC) Either Alone or in Combination With Pembrolizumab

• Status: Recruiting
• Trial end date: 2025-05-30
• Target enrollment: 0
• Participant gender: All

Summary

This trial will evaluate safety and efficacy of letetresgene autoleucel (GSK3377794) with or without pembrolizumab in participants with non-small cell lung cancer.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Pembrolizumab

Criteria

Inclusion Criteria:

• Age >=18 years on the day of signing informed consent.

• Histologically or cytologically diagnosed unresectable Stage IIIb or Stage IV NSCLC.

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

• Participant is positive for any of the following alleles: human leukocyte antigen (HLA)-A*02:01, HLA-A*02:05, and a) or HLA-A*02:06 by a validated test.

• Participant's tumor meets the pre-defined threshold for expression of NY-ESO-1 and/or LAGE-1a.

• Adequate organ function and blood cell counts, as defined in the protocol.

• Predicted life expectancy that is >=24 weeks from leukapheresis.

• Left ventricular ejection fraction >=45%.

• Prior therapies prior to lymphodepletion: a) All participants with NSCLC lacking actionable genetic aberrations, per National Comprehensive Cancer Network (NCCN) guidelines (Arms A and B), need to have received at least one line of programmed death protein 1/programmed death protein 1 ligand (PD-1/PD-L1) checkpoint blockade therapy. For participants in the metastatic setting, PD-1/PD-L1 checkpoint blockade therapy must have been received either alone, in combination or sequentially with platinum-containing chemotherapy. OR b) All participants with NSCLC with actionable genetic aberrations, per NCCN guidelines (Arm C only), should have received appropriate targeted therapy following NCCN or equivalent country-level guidelines.

• Disease progression at time of treatment, as defined in the protocol.

• Measurable disease at time of treatment per response evaluation criteria in solid tumors (RECIST) version 1.1 as assessed by local site investigator/radiology.

Exclusion Criteria:

• Prior gene therapy using an integrating vector.

• Prior allogeneic/autologous bone marrow or solid organ transplantation.

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, fludarabine, dimethylsulfoxide (DMSO) or other agents used in the study

• Severe hypersensitivity (>= Grade 3) to pembrolizumab and/or any of its excipients.

• Active autoimmune disease that has required systemic treatment in past 2 years.

• 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.

• Uncontrolled intercurrent illness.

• Participant has active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein Barr virus (EBV), cytomegalovirus (CMV), syphilis, or human T lymphotropic virus (HTLV), as defined in protocol.

• Known psychiatric or substance abuse disorders.

• Symptomatic or untreated central nervous system (CNS) metastases.

• Radiotherapy meeting any of the following criteria: a. >=50 Gray (Gy) to a significant volume of the pelvis, long bones or spine, or a cumulative dose of radiation that, in the investigator's opinion would predispose patients to prolonged cytopenia after lymphodepletion. b. Radiotherapy to the target lesions within 3 months before lymphodepletion. A lesion with unequivocal progression may be considered a target lesion regardless of time from last radiotherapy dose.

• Other protocol-defined inclusion/exclusion criteria may apply.