Trial Outcomes & Findings for A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma (NCT NCT01343043)

Last Updated: 2021-06-30

Results Overview

ORR was calculated as the percentage of participants with a confirmed complete response (CR) or partial response (PR) relative to the total number of participants in the analysis population per response evaluation criteria in solid tumors (RECIST) version (v)1.1 as determined by the local investigators.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

50 participants

Primary outcome timeframe

Up to 4.5 years

Results posted on

2021-06-30

Participant Flow

This study was designed to determine whether New York esophageal squamous cell carcinoma 1 (NY-ESO-1) specific genetically engineered T cells recognized a human leukocyte antigens (HLA-A2) binding peptide from NY-ESO-1 induced antitumor responses in participants with synovial sarcoma.

A total of 50 participants were enrolled in this study. Out of 50 participants, 45 participants received NY-ESO-1 genetically engineered T cell infusion.

Participant milestones

Participant milestones
Measure	Cohort 1: High NY-ESO-1 Expression Treated With Regimen A Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, intravenously \[IV\] and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A Participants with low tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, IV and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. Low tumor NY-ESO-1 expression was defined as \>=1+ by IHC in \>=1% cells but not to exceed 2+ or 3+ in \>=50% cells..	Cohort 3: High NY-ESO-1 Expression Treated With Regimen B Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen B (lymphodepleting chemotherapeutic agent; cyclophosphamide only on Days -3 and -2, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 4: High NY-ESO-1 Expression Treated With Regimen C Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen C (lymphodepleting chemotherapeutic agents; reduced dose of cyclophosphamide plus fludarabine on Days -7 to -5, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.
Overall Study STARTED	15	14	5	16
Overall Study Received T-cell Infusion	12	13	5	15
Overall Study COMPLETED	12	13	5	15
Overall Study NOT COMPLETED	3	1	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: High NY-ESO-1 Expression Treated With Regimen A Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, intravenously \[IV\] and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A Participants with low tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, IV and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. Low tumor NY-ESO-1 expression was defined as \>=1+ by IHC in \>=1% cells but not to exceed 2+ or 3+ in \>=50% cells..	Cohort 4: High NY-ESO-1 Expression Treated With Regimen C Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen C (lymphodepleting chemotherapeutic agents; reduced dose of cyclophosphamide plus fludarabine on Days -7 to -5, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.
Overall Study Disease progression before treatment	1	0	0
Overall Study Withdrawal by Subject	1	0	0
Overall Study Death	1	1	1

Baseline Characteristics

A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: High NY-ESO-1 Expression Treated With Regimen A n=15 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, intravenously \[IV\] and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A n=14 Participants Participants with low tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, IV and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. Low tumor NY-ESO-1 expression was defined as \>=1+ by IHC in \>=1% cells but not to exceed 2+ or 3+ in \>=50% cells..	Cohort 3: High NY-ESO-1 Expression Treated With Regimen B n=5 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen B (lymphodepleting chemotherapeutic agent; cyclophosphamide only on Days -3 and -2, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 4: High NY-ESO-1 Expression Treated With Regimen C n=16 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen C (lymphodepleting chemotherapeutic agents; reduced dose of cyclophosphamide plus fludarabine on Days -7 to -5, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Total n=50 Participants Total of all reporting groups
Age, Continuous	28.5 Years STANDARD_DEVIATION 10.00 • n=5 Participants	33.1 Years STANDARD_DEVIATION 16.18 • n=7 Participants	25.4 Years STANDARD_DEVIATION 8.73 • n=5 Participants	41.2 Years STANDARD_DEVIATION 13.80 • n=4 Participants	33.6 Years STANDARD_DEVIATION 14.00 • n=21 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	7 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants	25 Participants n=21 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	7 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants	25 Participants n=21 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Race/Ethnicity, Customized White	13 Participants n=5 Participants	11 Participants n=7 Participants	4 Participants n=5 Participants	15 Participants n=4 Participants	43 Participants n=21 Participants
Race/Ethnicity, Customized Missing	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to 4.5 years

Population: Modified intent-to-treat (mITT) Population comprised of all participants who received NY-ESO-1 genetically engineered T cell infusion

Outcome measures

Outcome measures
Measure	Cohort 1: High NY-ESO-1 Expression Treated With Regimen A n=12 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, intravenously \[IV\] and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A n=13 Participants Participants with low tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, IV and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. Low tumor NY-ESO-1 expression was defined as \>=1+ by IHC in \>=1% cells but not to exceed 2+ or 3+ in \>=50% cells..	Cohort 3: High NY-ESO-1 Expression Treated With Regimen B n=5 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen B (lymphodepleting chemotherapeutic agent; cyclophosphamide only on Days -3 and -2, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 4: High NY-ESO-1 Expression Treated With Regimen C n=15 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen C (lymphodepleting chemotherapeutic agents; reduced dose of cyclophosphamide plus fludarabine on Days -7 to -5, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.
Objective Response Rate (ORR)	50 Percentage of Participants	30.8 Percentage of Participants	20 Percentage of Participants	26.7 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 4.5 years

Population: mITT Population. Only those participants with data available at the specified data points were analyzed.

Duration of overall response (DOR) is defined as the time from first documented evidence of confirmed CR or confirmed PR until first documented date of disease progression or death due to any cause or surgical resection or start of prohibited medications. Duration of overall response was evaluated per RECIST v1.1. Median and full range of DOR are presented.

Outcome measures

Outcome measures
Measure	Cohort 1: High NY-ESO-1 Expression Treated With Regimen A n=6 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, intravenously \[IV\] and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A n=4 Participants Participants with low tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, IV and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. Low tumor NY-ESO-1 expression was defined as \>=1+ by IHC in \>=1% cells but not to exceed 2+ or 3+ in \>=50% cells..	Cohort 3: High NY-ESO-1 Expression Treated With Regimen B n=1 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen B (lymphodepleting chemotherapeutic agent; cyclophosphamide only on Days -3 and -2, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 4: High NY-ESO-1 Expression Treated With Regimen C n=4 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen C (lymphodepleting chemotherapeutic agents; reduced dose of cyclophosphamide plus fludarabine on Days -7 to -5, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.
Duration of Overall Response	31.0 Weeks Interval 13.0 to 72.0	8.6 Weeks Interval 8.0 to 13.0	32.1 Weeks Full range is not applicable due to single participant, and the median value presented here is the actual DOR for this single participant.	16.4 Weeks Interval 14.0 to 94.0

SECONDARY outcome

Timeframe: Up to 4.5 years

Population: mITT Population

Progression free survival is defined as the interval between the date of first T cell infusion and the earliest documented evidence of disease progression or death due to any cause or surgical resection or start of prohibited medications. Progression free survival was evaluated per RECIST v1.1. Median and inter-quartile range (first quartile and third quartile) of progression free survival are presented.

Outcome measures

Outcome measures
Measure	Cohort 1: High NY-ESO-1 Expression Treated With Regimen A n=12 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, intravenously \[IV\] and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A n=13 Participants Participants with low tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, IV and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. Low tumor NY-ESO-1 expression was defined as \>=1+ by IHC in \>=1% cells but not to exceed 2+ or 3+ in \>=50% cells..	Cohort 3: High NY-ESO-1 Expression Treated With Regimen B n=5 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen B (lymphodepleting chemotherapeutic agent; cyclophosphamide only on Days -3 and -2, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 4: High NY-ESO-1 Expression Treated With Regimen C n=15 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen C (lymphodepleting chemotherapeutic agents; reduced dose of cyclophosphamide plus fludarabine on Days -7 to -5, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.
Progression Free Survival	15.4 Weeks Interval 8.6 to 37.1	13.1 Weeks Interval 8.3 to 13.9	8.6 Weeks Interval 8.3 to 12.1	22.4 Weeks Interval 11.6 to 38.3

SECONDARY outcome

Timeframe: Up to 4.5 years

Population: mITT Population

Best overall response is the best response recorded from the start of treatment (first T cell infusion) until disease progression/recurrence. Response categories from best to worst are confirmed CR, confirmed PR, stable disease (SD) and confirmed progressive disease (PD). Best overall response is a stable disease, if CR or PR are unconfirmed. Data for number of participants with CR, PR, SD and PD are presented.

Outcome measures

Outcome measures
Measure	Cohort 1: High NY-ESO-1 Expression Treated With Regimen A n=12 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, intravenously \[IV\] and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A n=13 Participants Participants with low tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, IV and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. Low tumor NY-ESO-1 expression was defined as \>=1+ by IHC in \>=1% cells but not to exceed 2+ or 3+ in \>=50% cells..	Cohort 3: High NY-ESO-1 Expression Treated With Regimen B n=5 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen B (lymphodepleting chemotherapeutic agent; cyclophosphamide only on Days -3 and -2, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 4: High NY-ESO-1 Expression Treated With Regimen C n=15 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen C (lymphodepleting chemotherapeutic agents; reduced dose of cyclophosphamide plus fludarabine on Days -7 to -5, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.
Best Overall Response Complete response	1 Participants	0 Participants	0 Participants	0 Participants
Best Overall Response Partial response	5 Participants	4 Participants	1 Participants	4 Participants
Best Overall Response Stable disease	5 Participants	7 Participants	3 Participants	10 Participants
Best Overall Response Progressive disease	1 Participants	1 Participants	0 Participants	1 Participants
Best Overall Response Not evaluable	0 Participants	1 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 4.5 years

Population: mITT Population

Overall survival is defined as the interval between the date of the first T-cell infusion and date of death from any cause. Median and inter-quartile range (first quartile and third quartile) of overall survival are presented.

Outcome measures

Outcome measures
Measure	Cohort 1: High NY-ESO-1 Expression Treated With Regimen A n=12 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, intravenously \[IV\] and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A n=13 Participants Participants with low tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, IV and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. Low tumor NY-ESO-1 expression was defined as \>=1+ by IHC in \>=1% cells but not to exceed 2+ or 3+ in \>=50% cells..	Cohort 3: High NY-ESO-1 Expression Treated With Regimen B n=5 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen B (lymphodepleting chemotherapeutic agent; cyclophosphamide only on Days -3 and -2, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 4: High NY-ESO-1 Expression Treated With Regimen C n=15 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen C (lymphodepleting chemotherapeutic agents; reduced dose of cyclophosphamide plus fludarabine on Days -7 to -5, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.
Overall Survival	80.7 Weeks Interval 45.3 to 212.0	43.1 Weeks Interval 19.4 to 85.3	86.4 Weeks Interval 68.1 to 104.6	105.3 Weeks Interval 50.3 to \<75% of participants experienced the event within the treatment arm. Hence, third quartile could not be derived.

SECONDARY outcome

Timeframe: Up to 5 years

Population: Intent-to-treat (ITT) Population comprised of all participants who were enrolled in the study.

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function. Number of participants who had non-SAEs and SAEs are presented.

Outcome measures

Outcome measures
Measure	Cohort 1: High NY-ESO-1 Expression Treated With Regimen A n=15 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, intravenously \[IV\] and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A n=14 Participants Participants with low tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, IV and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. Low tumor NY-ESO-1 expression was defined as \>=1+ by IHC in \>=1% cells but not to exceed 2+ or 3+ in \>=50% cells..	Cohort 3: High NY-ESO-1 Expression Treated With Regimen B n=5 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen B (lymphodepleting chemotherapeutic agent; cyclophosphamide only on Days -3 and -2, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 4: High NY-ESO-1 Expression Treated With Regimen C n=16 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen C (lymphodepleting chemotherapeutic agents; reduced dose of cyclophosphamide plus fludarabine on Days -7 to -5, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) Non-SAE	15 Participants	13 Participants	5 Participants	15 Participants
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) SAE	9 Participants	7 Participants	4 Participants	6 Participants

SECONDARY outcome

Timeframe: Up to 4.5 years

Population: mITT Population

Blood samples were collected for the analysis of hematology parameters. No data collected separately for this outcome measure as any abnormal value would be recorded as an adverse event.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 4.5 years

Population: mITT Population

Blood samples were collected for the analysis of clinical chemistry parameters. No data collected separately for this outcome measure as any abnormal value would be recorded as an adverse event.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 4.5 years

Population: mITT Population. Only those participants with data available at the specified data points were analyzed.

Serum samples were collected for the determination of anti-infused (NY-ESO-1 genetically engineered T) cell antibodies (ATA) using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. A participant was considered to have a confirmed positive ATA result if they have a positive screening assay result and a positive confirmation assay result.

Outcome measures

Outcome measures
Measure	Cohort 1: High NY-ESO-1 Expression Treated With Regimen A n=10 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, intravenously \[IV\] and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A n=8 Participants Participants with low tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, IV and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. Low tumor NY-ESO-1 expression was defined as \>=1+ by IHC in \>=1% cells but not to exceed 2+ or 3+ in \>=50% cells..	Cohort 3: High NY-ESO-1 Expression Treated With Regimen B n=3 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen B (lymphodepleting chemotherapeutic agent; cyclophosphamide only on Days -3 and -2, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 4: High NY-ESO-1 Expression Treated With Regimen C n=8 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen C (lymphodepleting chemotherapeutic agents; reduced dose of cyclophosphamide plus fludarabine on Days -7 to -5, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.
Number of Participants With at Least One Confirmed Positive Post-Baseline Anti-infused (NY-ESO-1 Genetically Engineered T) Cell Antibody Result	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 4

Population: mITT Population.

CRS is a potentially life-threatening toxicity that is observed following administration of antibodies and adoptive T-cell therapies for cancer. Serum samples were collected to analyze the concentration of cytokines using the electrochemiluminescent tagged detection antibodies. The correlation between cytokines and cytokine release syndrome was considered between participants who had serious CRS vs no CRS or Non-serious CRS. There were only 4 participants across the whole study that had serious CRS and cytokine data was available for 3 of these participants. Due to the limited number of participants that had serious CRS no statistical correlations in cytokine levels and CRS could be performed. A listing of the levels of cytokines for the 3 participants with serious CRS is available/provided.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Week 4

Population: mITT Population.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Week 4

Population: mITT Population

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Week 4

Population: mITT Population.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 4.5 years

Population: mITT Population. Only those participants with data available at the specified data points were analyzed.

Time to maximum persistence is defined as date of maximum persistence for infusion visit minus date of first T cell infusion visit plus 1. Median and full range of time to maximum persistence are presented.

Outcome measures

Outcome measures
Measure	Cohort 1: High NY-ESO-1 Expression Treated With Regimen A n=6 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, intravenously \[IV\] and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A n=4 Participants Participants with low tumor expression of NY-ESO-1 underwent lymphodepletion with regimen A (lymphodepleting chemotherapeutic agents; cyclophosphamide plus fludarabine on Days -3 and -2, IV and only fludarabine on Days -5 and -4, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. Low tumor NY-ESO-1 expression was defined as \>=1+ by IHC in \>=1% cells but not to exceed 2+ or 3+ in \>=50% cells..	Cohort 3: High NY-ESO-1 Expression Treated With Regimen B n=1 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen B (lymphodepleting chemotherapeutic agent; cyclophosphamide only on Days -3 and -2, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.	Cohort 4: High NY-ESO-1 Expression Treated With Regimen C n=4 Participants Participants with high tumor expression of NY-ESO-1 underwent lymphodepletion with regimen C (lymphodepleting chemotherapeutic agents; reduced dose of cyclophosphamide plus fludarabine on Days -7 to -5, IV). Participants received one infusion of NY-ESO-1 genetically engineered T cells on Day 0. High tumor NY-ESO-1 expression was defined as 2+ or 3+ by immunohistochemistry (IHC) in \>=50% cells.
Time to Maximum Persistence of NY-ESO-1 Genetically Engineered T Cells	8.0 Days Interval 4.0 to 29.0	8.0 Days Interval 5.0 to 18.0	8.0 Days Interval 8.0 to 8.0	9 Days Interval 6.0 to 13.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to Day 21 (from first dose)

Population: mITT Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted.

DLT was planned to be evaluated. An event was to be considered a DLT if it occurred within the first 21 days of treatment, and met one of the protocol defined DLT criteria. The results for this outcome measure will never be posted.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 4.5 years

Population: mITT Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted.

Abnormal electrocardiogram, echocardiogram and multigated acquisition scan findings were planned to be evaluated. Clinical significance was based on the medical and scientific judgement of the investigator or qualified designee. The results for this outcome measure will never be posted.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 4.5 years

Population: mITT Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted.

Participants were planned to be evaluated for confirmed CR according to RECIST v1.1, after receiving a second dose of NY-ESO-1 genetically engineered T cell infusion. The results for this outcome measure will never be posted.

Outcome measures

Outcome data not reported

Adverse Events

Cohort 1: High NY-ESO-1 Expression Treated With Regimen A

Serious events: 9 serious events

Other events: 15 other events

Deaths: 12 deaths

Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A

Serious events: 7 serious events

Other events: 13 other events

Deaths: 13 deaths

Cohort 3: High NY-ESO-1 Expression Treated With Regimen B

Serious events: 4 serious events

Other events: 5 other events

Deaths: 4 deaths

Cohort 4: High NY-ESO-1 Expression Treated With Regimen C

Serious events: 6 serious events

Other events: 15 other events

Deaths: 8 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER