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

• ClinicalTrials.gov Identifier: NCT02588612
• Recruitment Status: Completed
• First Posted: October 28, 2015
• Last Update Posted: January 27, 2021
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Neoplasms	Drug: letetresgene autoleucel (GSK3377794); Drug: Cyclophosphamide; Drug: Fludarabine	Phase 1

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Open-Label Clinical Trial Evaluating the Safety and Efficacy of Autologous T Cells Expressing Enhanced TCRs Specific for NY-ESO-1 in Subjects With Stage IIIb or Stage IV Non-Small Cell Lung Cancer (NSCLC)
• Actual Study Start Date: February 1, 2016
• Actual Primary Completion Date: August 17, 2020
• Actual Study Completion Date: August 17, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: letetresgene autoleucel (GSK3377794); Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive letetresgene autoleucel (GSK3377794), as a single intravenous (IV) infusion after completing lymphodepleting chemotherapy.	Drug: letetresgene autoleucel (GSK3377794); letetresgene autoleucel (GSK3377794) as an IV infusion.; Drug: Cyclophosphamide; Cyclophosphamide will be used as a lymphodepleting chemotherapy.; Drug: Fludarabine; Fludarabine will be used as a lymphodepleting chemotherapy.

Outcome Measures

Primary Outcome Measures :

1. Number of participants with adverse events (AE), including serious adverse events (SAE) [ Time Frame: Up to 2 years ]
   All AEs and SAEs will be collected.
2. Number of participants with abnormal laboratory parameters [ Time Frame: Up to 2 years ]
   Blood samples will be collected for the assessment of hematology, chemistry and coagulation parameters.
3. Number of participants with abnormal electrocardiogram (ECG) findings [ Time Frame: Up to 2 years ]
   Number of participants with abnormal ECG parameters will be assessed.
4. Number of participants with abnormal pulse oximetry findings [ Time Frame: Up to 2 years ]
   Number of participants with abnormal pulse oximetry findings will be assessed.

Secondary Outcome Measures :

1. Overall Response rate (ORR) [ Time Frame: Up to 2 years ]
   Overall response rate is defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
2. Time to response (TTR) [ Time Frame: Up to 2 years ]
   Time to Response is defined as the time from date of T-cell infusion dose and the first documented evidence of response (CR or PR) in the subset of participants with a confirmed PR or CR as the best overall response (BOR) as assessed by the RECIST 1.1.
3. Duration of response (DOR) [ Time Frame: Up to 2 years ]
   Duration of response is defined as the time from first documented evidence of CR or PR until first documented disease progression or death due to any cause.
4. Disease control rate (DCR) [ Time Frame: Up to 2 years ]
   Disease control rate is defined as the percentage of participants with a confirmed stable disease (SD) or better as the BOR (PR, CR, or SD more than or equal to [>=]12 weeks).
5. Progression free survival (PFS) [ Time Frame: Up to 2 years ]
   Progression free survival is defined as the time from the date of T-cell infusion until the earliest date of disease progression or death due to any cause.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Florida

GSK Investigational Site

Miami, Florida, United States, 33136

GSK Investigational Site

Tampa, Florida, United States, 33612

United States, Texas

GSK Investigational Site

Houston, Texas, United States, 77030

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02588612
• Other Study ID Numbers: 208749; ADP-0011-004 ( Other Identifier: Adaptimmune Therapeutics ); 2016-002517-21 ( EudraCT Number )
• First Posted: October 28, 2015
• Last Update Posted: January 27, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• URL: http://clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:

Letetresgene autoleucel; Adoptive TCR T-cell therapy; NY-ESO-1; T Cell Receptor; Non-Small Cell Lung Cancer; Leukapheresis

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Cyclophosphamide; Fludarabine; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists