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

• Status: Completed
• Trial end date: 2020-08-10
• Target enrollment: 0
• Participant gender: All

Summary

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

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

Details

• Lead Sponsor: GlaxoSmithKline
• Treatments: Cyclophosphamide; Fludarabine

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.