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

NCT02588612 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 208749ADP-0011-0042016-002517-21
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Neoplasms

Keywords

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

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or is clinically significant or requires intervention to prevent one of the outcomes listed before. Number of participants with common (greater than or equal to \[\>=\]5 percent\[%\]) non-serious AEs and SAEs are presented.

  Up to 24 months

• Number of Participants With Hematology Results by Maximum Grade Increase Post-Baseline

  Blood samples were collected for the analysis of following hematology parameters: hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. Laboratory parameters were graded according to National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4.03 where, Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline is the most recent, non-missing value from a central laboratory within 7 days prior to the lymphodepleting chemotherapy. An increase in grade is defined as an increase in CTCAE grade relative to Baseline grade. Data for any grade increase at worst-case post-Baseline is presented

  Up to 24 months

• Number of Participants With Any Grade Increase in Clinical Chemistry Parameters

  Blood samples were collected for analysis of clinical chemistry parameters: glucose (Gl), albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin (Bil), creatinine (Creat), potassium (Pot), magnesium (Mg), phosphate (Ph), sodium (Sod) and calcium. Laboratory parameters were graded according to NCI-CTCAE version 4.03 where, Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. An increase in grade is defined as an increase in CTCAE grade relative to Baseline grade. Data for any grade increase at worst-case post-Baseline is presented.

  Up to 24 months

• Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings

  12-lead ECGs were recorded in semi-supine position after 5 minutes rest using an ECG machine that automatically calculated the heart rate and measured PR, RR, QRS and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Data for number of participants with abnormal not clinically significant (NCS) and clinically significant (CS) ECG findings for worst case post-Baseline have been presented. Clinically significant abnormal laboratory findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

  Up to 24 months

• Change From Baseline in Oxygen Saturation

  Oxygen saturation measures the capacity of blood to transport oxygen to other parts of the body. Oxygen saturation was measured using a pulse oximeter. Baseline is the most recent, non-missing value within 7 days prior to initiating the lymphodepleting chemotherapy. Change from Baseline is the post-Baseline visit value minus Baseline value.

  Baseline, Day 1 (pre-dose, 5, 15, and 30 minutes, 1, 1.5, 2, and 4 hours post dose), Days 2, 3, 4, 5, 8 and Week 2

Secondary Outcomes (5)

• Overall Response Rate (ORR)

  Up to 24 Months

• Time to Response

  Up to 24 months

• Duration of Response

  Up to 24 months

• Disease Control Rate (DCR)

  Up to 24 months

• Progression-Free Survival (PFS) by Investigator Assessment

  Up to 24 months

Study Arms (1)

letetresgene autoleucel (GSK3377794)

EXPERIMENTAL

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); Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

letetresgene autoleucel (GSK3377794) DRUG

letetresgene autoleucel (GSK3377794) as an IV infusion.

letetresgene autoleucel (GSK3377794)

Cyclophosphamide DRUG

Cyclophosphamide will be used as a lymphodepleting chemotherapy.

letetresgene autoleucel (GSK3377794)

Fludarabine DRUG

Fludarabine will be used as a lymphodepleting chemotherapy.

letetresgene autoleucel (GSK3377794)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (3)

GSK Investigational Site

Miami, Florida, 33136, United States

Location

GSK Investigational Site

Tampa, Florida, 33612, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2015
• First Posted: October 28, 2015
• Study Start: February 1, 2016
• Primary Completion: August 10, 2020
• Study Completion: August 10, 2020
• Last Updated: September 5, 2021
• Results First Posted: September 5, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

US (3)