letetresgene autoleucel engineered t cells in ny-eso -1 positive advanced non-small cell lung cancer (nsclc)

Conditions: Neoplasms

Summary: this trial will evaluate safety and efficacy of letetresgene autoleucel (gsk3377794) in participants with metastatic nsclc.

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.

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.

Keywords: letetresgene autoleucel adoptive tcr t-cell therapy ny-eso-1 t cell receptor non-small cell lung cancer leukapheresis