©2022 Stanford Medicine
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
Trial ID: NCT03709706
This trial will evaluate safety and tolerability of letetresgene autoleucel (GSK3377794) with or without pembrolizumab in participants with non-small cell lung cancer.
A Phase 1b/2a Pilot Study to Evaluate the Safety and Tolerability of Autologous T-Cells Expressing Enhanced TCRs (T Cell Receptors) Specific for NY-ESO-1/LAGE-1a (GSK3377794) Alone, or in Combination With Pembrolizumab in HLA-A2+ Participants With NY-ESO-1- or LAGE-1a-Positive Advanced or Recurrent Non-Small Cell Lung Cancer
- 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
- 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.
- 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
- 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
- Other protocol-defined inclusion/exclusion criteria may apply.
School of Medicine
300 Pasteur Drive
Stanford, CA 94305