Pilot Immunotherapy Study With Letetresgene Autoleucel (Lete-cel, GSK3377794)T-cells in New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1)/ LAGE-1a-positive Advanced Non-small Cell Lung Cancer (NSCLC) Either Alone or in Combination With Pembrolizumab
Condition: Neoplasms
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Lete-cel; Pembrolizumab
Intervention description: lete-cel will be administered to eligible participants.; Pembrolizumab will be administered to eligible participants.
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants will receive GSK3377794, either as monotherapy or in combination with pembrolizumab.
Masking: None (Open Label)
Masking description: This will be an open-label study. Hence, there will be no masking.
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: GSK3377794; Pembrolizumab; T Cell Receptors; Adoptive T-cell therapy; Non-Small Cell Lung Cancer; Immuno-oncology; NY-ESO-1; LAGE-1a; Leukapheresis; Letetresgene autoleucel

Summary:

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

Eligibility 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 treatment: Previous treatment with genetically engineered NY-ESO-1-specific
             T-cells. Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody. 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 that involves the lung (Percentage of normal lung receiving at least 20
             Gray [Gy] during radiotherapy [V20] exceeding 30% lung volume or mean heart dose >20
             Gy) within 3 months or radiotherapy (including but not limited to palliative
             radiotherapy) to lung/mediastinum with V20 less than 30% lung volume and with mean
             heart dose <=20 Gy within 4 weeks (+/- 3 days).

          -  Radiotherapy of >=50 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
             participants to prolonged cytopenia after lymphodepletion.

          -  All of the participant's measurable lesions have been irradiated within 3 months
             before lymphodepletion.

          -  Other protocol-defined inclusion/exclusion criteria may apply.