A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma
Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT01343043
Collaborator
(none)
50
8
4
80.7
6.3
0.1
Study Details
Study Description
Brief Summary
The purpose of this early (pilot) clinical trial is to test the effects (both good and bad) of chemotherapy and adoptive immunotherapy with T cells engineered to recognize NY-ESO-1 peptide in patients with unresectable, metastatic or recurrent synovial sarcoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
Design
-
Patients will undergo apheresis at the enrolling institution. PBMC will be shipped to a central manufacturer for gene transduction, activation and expansion, then cryopreserved and shipped back to the enrolling institution.
-
The trial seeks to enroll up to 65 patients, that is, up to 20 patients in Cohort 1 and up to 15 patients in Cohorts 2-4. Depending on the cohort patients are enrolled in, patients will undergo lymphodepletion with cyclophosphamide with or without fludarabine.
-
Cohort 1: Complete
-
Cohort 2: Up to 15 patients may be enrolled to achieve at least 10 evaluable patients treated with NY-ESO-1ᶜ²⁵⁹T. Patients will undergo lymphodepletion with cyclophosphamide plus fludarabine on Days -3 and -2, and without fludarabine on Days -5 and -4.
-
Cohort 3: Up to 15 patients may be enrolled to achieve at least 10 evaluable patients treated with NY-ESO-1ᶜ²⁵⁹T. Patients will undergo lymphodepletion with cyclophosphamide only on Days -3 and -2. (Cohort Complete)
-
Cohort 4: Up to 15 patients may be enrolled to achieve at least 5 evaluable patients treated with NY-ESO-1ᶜ²⁵⁹T. Patients will undergo lymphodepletion with cyclophosphamide plus fludarabine on Days -7 to -5.
On Day 0, patients ≥40 kg will receive the minimum cell dose of at least 1x10⁹ transduced NY-ESO-1ᶜ²⁵⁹T cells with a maximum of 6x10⁹ transduced cells. The target dose for this protocol is 5x10⁹ transduced NY-ESO-1ᶜ²⁵⁹T cells. Patients <40 kg will be dosed per body weight with a minimum 0.025x10⁹ transduced cells/kg, with a target dose of 0.125 x10⁹ transduced cells/kg.
-
Patients will be monitored for toxicity, antitumor effects and immune endpoints.
-
Patients who have a confirmed response, or have stable disease for >3 months then progress may receive a 2nd T cell infusion, provided eligibility criteria are met. The 2nd treatment cell infusion will be administered in the same manner as the first. Patients who meet the eligibility criteria may receive a 2nd infusion of NY-ESO-1ᶜ²⁵⁹T no sooner than 60 days and no later than 2 years following completion of the first treatment.
Study Design
Study Type:
Interventional
Actual Enrollment
:
50 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Primary Purpose:
Treatment
Official Title:
A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma
Actual Study Start Date
:
Sep 27, 2012
Actual Primary Completion Date
:
Jun 18, 2019
Actual Study Completion Date
:
Jun 18, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1 treated with NY-ESO-1 T Cells High NY-ESO-1 expression and the use of cyclophosphamide plus fludarabine as the lymphodepleting chemotherapy. |
Drug: NY-ESO-1(c259)T Cells
Lymphodepleting chemotherapy followed by infusion with NY-ESO-1(c259) transduced autologous T cells. Subjects will receive one infusion of NY-ESO-1 genetically engineered T cells on Day 0.
Drug: Fludarabine
Fludarabine will be used as lymphodepleting chemotherapy.
Drug: Cyclophosphamide
Cyclophosphamide will be used as lymphodepleting chemotherapy.
|
| Experimental: Cohort 2 treated with NY-ESO-1 T Cells Low NY-ESO-1 expression and the use of cyclophosphamide plus fludarabine as the lymphodepleting chemotherapy. |
Drug: NY-ESO-1(c259)T Cells
Lymphodepleting chemotherapy followed by infusion with NY-ESO-1(c259) transduced autologous T cells. Subjects will receive one infusion of NY-ESO-1 genetically engineered T cells on Day 0.
Drug: Fludarabine
Fludarabine will be used as lymphodepleting chemotherapy.
Drug: Cyclophosphamide
Cyclophosphamide will be used as lymphodepleting chemotherapy.
|
| Experimental: Cohort 3 treated with NY-ESO-1 T Cells High NYESO-1 expression and the use of cyclophosphamide only for lymphodepletion rather than fludarabine as the lymphodepleting chemotherapy. |
Drug: NY-ESO-1(c259)T Cells
Lymphodepleting chemotherapy followed by infusion with NY-ESO-1(c259) transduced autologous T cells. Subjects will receive one infusion of NY-ESO-1 genetically engineered T cells on Day 0.
Drug: Cyclophosphamide
Cyclophosphamide will be used as lymphodepleting chemotherapy.
|
| Experimental: Cohort 4 treated with NY-ESO-1 T Cells High NY-ESO-1 expression and the use of reduced dose cyclophosphamide plus fludarabine regimen as the lymphodepleting chemotherapy. |
Drug: NY-ESO-1(c259)T Cells
Lymphodepleting chemotherapy followed by infusion with NY-ESO-1(c259) transduced autologous T cells. Subjects will receive one infusion of NY-ESO-1 genetically engineered T cells on Day 0.
Drug: Fludarabine
Fludarabine will be used as lymphodepleting chemotherapy.
Drug: Cyclophosphamide
Cyclophosphamide will be used as lymphodepleting chemotherapy.
|
Outcome Measures
Primary Outcome Measures
- Objective Response Rate (ORR) [Up to 4.5 years]
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.
Secondary Outcome Measures
- Duration of Overall Response [Up to 4.5 years]
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.
- Progression Free Survival [Up to 4.5 years]
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.
- Best Overall Response [Up to 4.5 years]
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.
- Overall Survival [Up to 4.5 years]
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.
- Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) [Up to 5 years]
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.
- Number of Participants With Worst Post-Baseline Grade Results for Hematology Parameters [Up to 4.5 years]
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.
- Number of Participants With Worst Post-Baseline Grade Results for Clinical Chemistry Parameters [Up to 4.5 years]
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.
- Number of Participants With at Least One Confirmed Positive Post-Baseline Anti-infused (NY-ESO-1 Genetically Engineered T) Cell Antibody Result [Up to 4.5 years]
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.
- Concentration of Cytokines in Cytokine Release Syndrome (CRS) by CRS Status: Cohort 1: High NY-ESO-1 Expression Treated With Regimen A [Up to Week 4]
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.
- Concentration of Cytokines in CRS by CRS Status: Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A [Up to Week 4]
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.
- Concentration of Cytokines in CRS by CRS Status: Cohort 3: High NY-ESO-1 Expression Treated With Regimen B [Up to Week 4]
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.
- Concentration of Cytokines in CRS by CRS Status: Cohort 4: High NY-ESO-1 Expression Treated With Regimen C [Up to Week 4]
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.
- Time to Maximum Persistence of NY-ESO-1 Genetically Engineered T Cells [Up to 4.5 years]
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.
Other Outcome Measures
- Number of Participants With Dose-limiting Toxicities (DLTs) [Up to Day 21 (from first dose)]
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.
- Number of Participants With Clinically Significant Abnormal Electrocardiogram, Echocardiogram and Multigated Acquisition Scan Findings [Up to 4.5 years]
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.
- Percentage of Participants With Confirmed CR [Up to 4.5 years]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
4 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Synovial sarcoma that has been treated with standard chemotherapy containing ifosfamide and/or doxorubicin and remains: unresectable or metastatic or progressive/persistent or recurrent disease
-
Measurable disease
-
Patients must have proven positive tumor sample for NY-ESO-1 as follows:
-
Cohort 1 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ≥ 50% of cells.
-
Cohort 2 -Positive expression is defined as ≥1+ by immunohistochemistry in ≥1% cells, but not to exceed 2+ and/or 3+ in ≥ 50% of cells.
-
Cohort 3 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ≥ 50% of cells.
-
Cohort 4 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ≥ 50% of cells.
-
HLA-A02:01, HLA-A02:05, and/or HLA-A*02:06 by high resolution testing at a local or central laboratory
-
Weigh more than 18 kg
-
All previous cytotoxic chemotherapy, monoclonal antibody therapy, or immune therapy must be washed out 3 weeks before apheresis and must be completed at least 3 weeks prior to pre-infusion lymphodepletive chemotherapy.
-
Systemic corticosteroid or other immunosuppressive therapy should be washed out 2 weeks before apheresis and must be completed at least 2 weeks prior to pre-infusion lymphodepletive chemotherapy.
-
Biologic or other approved molecular targeted small molecule inhibitors should be washed out 1 week or 5 half-lives (whichever is longer) before apheresis and must be completed at least 1 week or 5 half-lives (whichever is longer) prior to pre-infusion lymphodepletive chemotherapy.
-
Any grade 3 or 4 hematologic toxicity of any previous therapy must have resolved to grade 2 or less prior to apheresis and any grade 3 or 4 toxicity must have resolved to grade 2 or less prior to pre-infusion lymphodepletive chemotherapy.
-
ECOG 0-1, or for children ≤10 years of age, Lansky > 60
-
Life expectancy > 3 months
-
Left ventricular ejection fraction ≥ 40% or fractional shortening ≥ 28%
-
- bilirubin < 2 mg/dl (Patients with Gilbert Syndrome total bilirubin <3xULN and direct bilirubin ≤ 35%)
-
AST, ALT ≤ 2.5 x upper limit of normal
-
ANC ≥ 1.0 x 10⁹/L
-
Platelets ≥ 75 x 10⁹/L
-
Age-adjusted normal serum creatinine or a creatinine clearance ≥ 40 ml/min
-
Ability to give informed consent for patients greater than 18 years of age. For patients less than 18 years of age the legal guardian must give informed consent.
-
Male patients must be willing to practice birth control (including abstinence) during and for 4 months after treatment. Female patients must be willing to practice birth control (including abstinence) during treatment and for 4 months after gene modified cells are no longer detected in body.
Exclusion Criteria:
- Active HIV, HBV, HCV or HTLV 1/2 infection (due to increased risk of complications during lymphodepleting regimen and confounding effects on the immune system). Active hepatitis B or C infection is defined by seropositive for hepatitis B surface antigen (HbSAg) or hepatitis C antibody.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Duarte | California | United States | 91010 |
| 2 | GSK Investigational Site | Miami | Florida | United States | 33136 |
| 3 | GSK Investigational Site | Tampa | Florida | United States | 33612 |
| 4 | GSK Investigational Site | Bethesda | Maryland | United States | 20892 |
| 5 | GSK Investigational Site | Boston | Massachusetts | United States | 02114 |
| 6 | GSK Investigational Site | Saint Louis | Missouri | United States | 63110 |
| 7 | GSK Investigational Site | New York | New York | United States | 10065 |
| 8 | GSK Investigational Site | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01343043
Other Study ID Numbers:
- 208466
- ADP 04511
- 2015-005594-21
First Posted:
Apr 27, 2011
Last Update Posted:
Jun 30, 2021
Last Verified:
Jun 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Keywords provided by GlaxoSmithKline
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | 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. |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | Cohort 1: High NY-ESO-1 Expression Treated With Regimen A | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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.. | 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. | 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. |
| Period Title: Overall Study | ||||
| STARTED | 15 | 14 | 5 | 16 |
| Received T-cell Infusion | 12 | 13 | 5 | 15 |
| COMPLETED | 12 | 13 | 5 | 15 |
| NOT COMPLETED | 3 | 1 | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | Cohort 1: High NY-ESO-1 Expression Treated With Regimen A | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C | Total |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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.. | 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. | 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 of all reporting groups |
| Overall Participants | 15 | 14 | 5 | 16 | 50 |
| Age (Years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Years] |
28.5
(10.00)
|
33.1
(16.18)
|
25.4
(8.73)
|
41.2
(13.80)
|
33.6
(14.00)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
8
53.3%
|
7
50%
|
2
40%
|
8
50%
|
25
50%
|
| Male |
7
46.7%
|
7
50%
|
3
60%
|
8
50%
|
25
50%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||
| Asian |
0
0%
|
1
7.1%
|
0
0%
|
0
0%
|
1
2%
|
| Black or African American |
1
6.7%
|
0
0%
|
1
20%
|
1
6.3%
|
3
6%
|
| White |
13
86.7%
|
11
78.6%
|
4
80%
|
15
93.8%
|
43
86%
|
| Missing |
1
6.7%
|
2
14.3%
|
0
0%
|
0
0%
|
3
6%
|
Outcome Measures
| Title | Objective Response Rate (ORR) |
|---|---|
| Description | 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. |
| Time Frame | Up to 4.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified intent-to-treat (mITT) Population comprised of all participants who received NY-ESO-1 genetically engineered T cell infusion |
| Arm/Group Title | Cohort 1: High NY-ESO-1 Expression Treated With Regimen A | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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.. | 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. | 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. |
| Measure Participants | 12 | 13 | 5 | 15 |
| Number [Percentage of Participants] |
50
333.3%
|
30.8
220%
|
20
400%
|
26.7
166.9%
|
| Title | Duration of Overall Response |
|---|---|
| Description | 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. |
| Time Frame | Up to 4.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population. Only those participants with data available at the specified data points were analyzed. |
| Arm/Group Title | Cohort 1: High NY-ESO-1 Expression Treated With Regimen A | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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.. | 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. | 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. |
| Measure Participants | 6 | 4 | 1 | 4 |
| Median (Full Range) [Weeks] |
31.0
|
8.6
|
32.1
|
16.4
|
| Title | Progression Free Survival |
|---|---|
| Description | 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. |
| Time Frame | Up to 4.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population |
| Arm/Group Title | Cohort 1: High NY-ESO-1 Expression Treated With Regimen A | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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.. | 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. | 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. |
| Measure Participants | 12 | 13 | 5 | 15 |
| Median (Inter-Quartile Range) [Weeks] |
15.4
|
13.1
|
8.6
|
22.4
|
| Title | Best Overall Response |
|---|---|
| Description | 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. |
| Time Frame | Up to 4.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population |
| Arm/Group Title | Cohort 1: High NY-ESO-1 Expression Treated With Regimen A | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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.. | 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. | 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. |
| Measure Participants | 12 | 13 | 5 | 15 |
| Complete response |
1
6.7%
|
0
0%
|
0
0%
|
0
0%
|
| Partial response |
5
33.3%
|
4
28.6%
|
1
20%
|
4
25%
|
| Stable disease |
5
33.3%
|
7
50%
|
3
60%
|
10
62.5%
|
| Progressive disease |
1
6.7%
|
1
7.1%
|
0
0%
|
1
6.3%
|
| Not evaluable |
0
0%
|
1
7.1%
|
1
20%
|
0
0%
|
| Title | Overall Survival |
|---|---|
| Description | 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. |
| Time Frame | Up to 4.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population |
| Arm/Group Title | Cohort 1: High NY-ESO-1 Expression Treated With Regimen A | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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.. | 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. | 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. |
| Measure Participants | 12 | 13 | 5 | 15 |
| Median (Inter-Quartile Range) [Weeks] |
80.7
|
43.1
|
86.4
|
105.3
|
| Title | Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) |
|---|---|
| Description | 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. |
| Time Frame | Up to 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) Population comprised of all participants who were enrolled in the study. |
| Arm/Group Title | Cohort 1: High NY-ESO-1 Expression Treated With Regimen A | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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.. | 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. | 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. |
| Measure Participants | 15 | 14 | 5 | 16 |
| Non-SAE |
15
100%
|
13
92.9%
|
5
100%
|
15
93.8%
|
| SAE |
9
60%
|
7
50%
|
4
80%
|
6
37.5%
|
| Title | Number of Participants With Worst Post-Baseline Grade Results for Hematology Parameters |
|---|---|
| Description | 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. |
| Time Frame | Up to 4.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population |
| Arm/Group Title | Cohort 1: High NY-ESO-1 Expression Treated With Regimen A | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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.. | 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. | 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. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Number of Participants With Worst Post-Baseline Grade Results for Clinical Chemistry Parameters |
|---|---|
| Description | 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. |
| Time Frame | Up to 4.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population |
| Arm/Group Title | Cohort 1: High NY-ESO-1 Expression Treated With Regimen A | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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.. | 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. | 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. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Number of Participants With at Least One Confirmed Positive Post-Baseline Anti-infused (NY-ESO-1 Genetically Engineered T) Cell Antibody Result |
|---|---|
| Description | 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. |
| Time Frame | Up to 4.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population. Only those participants with data available at the specified data points were analyzed. |
| Arm/Group Title | Cohort 1: High NY-ESO-1 Expression Treated With Regimen A | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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.. | 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. | 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. |
| Measure Participants | 10 | 8 | 3 | 8 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Concentration of Cytokines in Cytokine Release Syndrome (CRS) by CRS Status: Cohort 1: High NY-ESO-1 Expression Treated With Regimen A |
|---|---|
| Description | 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. |
| Time Frame | Up to Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population. |
| Arm/Group Title | Cohort 1: High NY-ESO-1 Expression Treated With Regimen A |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 0 |
| Title | Concentration of Cytokines in CRS by CRS Status: Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A |
|---|---|
| Description | 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. |
| Time Frame | Up to Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population. |
| Arm/Group Title | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A |
|---|---|
| Arm/Group Description | 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.. |
| Measure Participants | 0 |
| Title | Concentration of Cytokines in CRS by CRS Status: Cohort 3: High NY-ESO-1 Expression Treated With Regimen B |
|---|---|
| Description | 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. |
| Time Frame | Up to Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population |
| Arm/Group Title | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 0 |
| Title | Concentration of Cytokines in CRS by CRS Status: Cohort 4: High NY-ESO-1 Expression Treated With Regimen C |
|---|---|
| Description | 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. |
| Time Frame | Up to Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population. |
| Arm/Group Title | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 0 |
| Title | Time to Maximum Persistence of NY-ESO-1 Genetically Engineered T Cells |
|---|---|
| Description | 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. |
| Time Frame | Up to 4.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population. Only those participants with data available at the specified data points were analyzed. |
| Arm/Group Title | Cohort 1: High NY-ESO-1 Expression Treated With Regimen A | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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.. | 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. | 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. |
| Measure Participants | 6 | 4 | 1 | 4 |
| Median (Full Range) [Days] |
8.0
|
8.0
|
8.0
|
9
|
| Title | Number of Participants With Dose-limiting Toxicities (DLTs) |
|---|---|
| Description | 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. |
| Time Frame | Up to Day 21 (from first dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. |
| Arm/Group Title | Cohort 1: High NY-ESO-1 Expression Treated With Regimen A | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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.. | 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. | 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. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Number of Participants With Clinically Significant Abnormal Electrocardiogram, Echocardiogram and Multigated Acquisition Scan Findings |
|---|---|
| Description | 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. |
| Time Frame | Up to 4.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. |
| Arm/Group Title | Cohort 1: High NY-ESO-1 Expression Treated With Regimen A | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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.. | 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. | 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. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Percentage of Participants With Confirmed CR |
|---|---|
| Description | 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. |
| Time Frame | Up to 4.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. |
| Arm/Group Title | Cohort 1: High NY-ESO-1 Expression Treated With Regimen A | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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.. | 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. | 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. |
| Measure Participants | 0 | 0 | 0 | 0 |
Adverse Events
| Time Frame | Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment (Day 1) until maximum of 4.5 years | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | SAEs and non-serious AEs were reported for the ITT Population which comprised of all participants who were enrolled in the study. | |||||||
| Arm/Group Title | Cohort 1: High NY-ESO-1 Expression Treated With Regimen A | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C | ||||
| Arm/Group Description | 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. | 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. | 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. | 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. | ||||
All Cause Mortality |
||||||||
| Cohort 1: High NY-ESO-1 Expression Treated With Regimen A | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 12/15 (80%) | 13/14 (92.9%) | 4/5 (80%) | 8/16 (50%) | ||||
Serious Adverse Events |
||||||||
| Cohort 1: High NY-ESO-1 Expression Treated With Regimen A | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/15 (60%) | 7/14 (50%) | 4/5 (80%) | 6/16 (37.5%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Febrile neutropenia | 2/15 (13.3%) | 1/14 (7.1%) | 0/5 (0%) | 2/16 (12.5%) | ||||
| Bone marrow failure | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Anaemia | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Neutropenia | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Cardiac disorders | ||||||||
| Myocardial infarction | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Pericardial effusion | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Supraventricular tachycardia | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Diarrhoea | 0/15 (0%) | 2/14 (14.3%) | 0/5 (0%) | 0/16 (0%) | ||||
| Abdominal pain | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Anal ulcer | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Enterocolitis | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Nausea | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Proctalgia | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Vomiting | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| General disorders | ||||||||
| Pyrexia | 4/15 (26.7%) | 1/14 (7.1%) | 0/5 (0%) | 3/16 (18.8%) | ||||
| Chills | 2/15 (13.3%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Chest pain | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Non-cardiac chest pain | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Cholecystitis acute | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Immune system disorders | ||||||||
| Cytokine release syndrome | 1/15 (6.7%) | 3/14 (21.4%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Infections and infestations | ||||||||
| Bacteraemia | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Cytomegalovirus infection | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Device related infection | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Lung infection | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Vascular access complication | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Investigations | ||||||||
| Neutrophil count decreased | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Platelet count decreased | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| White blood cell count decreased | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Hypokalaemia | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Leukaemia | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Tumour haemorrhage | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Tumour pain | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Nervous system disorders | ||||||||
| Guillain-Barre syndrome | 0/15 (0%) | 2/14 (14.3%) | 0/5 (0%) | 0/16 (0%) | ||||
| Spinal cord compression | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnoea | 2/15 (13.3%) | 1/14 (7.1%) | 2/5 (40%) | 0/16 (0%) | ||||
| Pneumothorax | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 2/16 (12.5%) | ||||
| Hypoxia | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Pleural effusion | 0/15 (0%) | 1/14 (7.1%) | 1/5 (20%) | 0/16 (0%) | ||||
| Respiratory failure | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Cough | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Haemoptysis | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Pleuritic pain | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Pneumonitis | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Pulmonary haemorrhage | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Rash maculo-papular | 2/15 (13.3%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Vascular disorders | ||||||||
| Embolism | 2/15 (13.3%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Hypotension | 0/15 (0%) | 3/14 (21.4%) | 0/5 (0%) | 0/16 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Cohort 1: High NY-ESO-1 Expression Treated With Regimen A | Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A | Cohort 3: High NY-ESO-1 Expression Treated With Regimen B | Cohort 4: High NY-ESO-1 Expression Treated With Regimen C | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 15/15 (100%) | 13/14 (92.9%) | 5/5 (100%) | 15/16 (93.8%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 14/15 (93.3%) | 13/14 (92.9%) | 4/5 (80%) | 9/16 (56.3%) | ||||
| Febrile neutropenia | 3/15 (20%) | 4/14 (28.6%) | 0/5 (0%) | 6/16 (37.5%) | ||||
| Neutropenia | 0/15 (0%) | 3/14 (21.4%) | 1/5 (20%) | 7/16 (43.8%) | ||||
| Thrombocytopenia | 1/15 (6.7%) | 5/14 (35.7%) | 0/5 (0%) | 4/16 (25%) | ||||
| Leukopenia | 0/15 (0%) | 3/14 (21.4%) | 0/5 (0%) | 0/16 (0%) | ||||
| Leukocytosis | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 2/16 (12.5%) | ||||
| Cardiac disorders | ||||||||
| Sinus tachycardia | 7/15 (46.7%) | 7/14 (50%) | 2/5 (40%) | 4/16 (25%) | ||||
| Tachycardia | 4/15 (26.7%) | 4/14 (28.6%) | 2/5 (40%) | 6/16 (37.5%) | ||||
| Pericardial effusion | 1/15 (6.7%) | 0/14 (0%) | 2/5 (40%) | 1/16 (6.3%) | ||||
| Sinus bradycardia | 2/15 (13.3%) | 1/14 (7.1%) | 1/5 (20%) | 0/16 (0%) | ||||
| Atrial fibrillation | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Palpitations | 2/15 (13.3%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Right ventricular dysfunction | 0/15 (0%) | 0/14 (0%) | 2/5 (40%) | 0/16 (0%) | ||||
| Angina pectoris | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Aortic valve disease | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Arrhythmia | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Atrial flutter | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Bradycardia | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Cardiac tamponade | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Cardiomyopathy | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Mitral valve disease | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Pulmonary valve disease | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Tricuspid valve disease | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Ear pain | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Eustachian tube dysfunction | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| External ear inflammation | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Endocrine disorders | ||||||||
| Hyperthyroidism | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Hypothyroidism | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Eye disorders | ||||||||
| Vision blurred | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 2/16 (12.5%) | ||||
| Dry eye | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Eye pruritus | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Eyelid ptosis | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Periorbital oedema | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Photophobia | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Nausea | 13/15 (86.7%) | 10/14 (71.4%) | 4/5 (80%) | 13/16 (81.3%) | ||||
| Diarrhoea | 8/15 (53.3%) | 9/14 (64.3%) | 2/5 (40%) | 5/16 (31.3%) | ||||
| Vomiting | 7/15 (46.7%) | 6/14 (42.9%) | 3/5 (60%) | 6/16 (37.5%) | ||||
| Constipation | 8/15 (53.3%) | 3/14 (21.4%) | 3/5 (60%) | 7/16 (43.8%) | ||||
| Abdominal pain | 4/15 (26.7%) | 4/14 (28.6%) | 3/5 (60%) | 3/16 (18.8%) | ||||
| Dyspepsia | 1/15 (6.7%) | 2/14 (14.3%) | 1/5 (20%) | 3/16 (18.8%) | ||||
| Abdominal distension | 1/15 (6.7%) | 1/14 (7.1%) | 1/5 (20%) | 2/16 (12.5%) | ||||
| Dysphagia | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 3/16 (18.8%) | ||||
| Proctalgia | 3/15 (20%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Abdominal pain upper | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Dry mouth | 0/15 (0%) | 1/14 (7.1%) | 1/5 (20%) | 1/16 (6.3%) | ||||
| Gastritis | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Gastrooesophageal reflux disease | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 2/16 (12.5%) | ||||
| Stomatitis | 2/15 (13.3%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Lip dry | 0/15 (0%) | 2/14 (14.3%) | 0/5 (0%) | 0/16 (0%) | ||||
| Oral dysaesthesia | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Oral mucosal erythema | 0/15 (0%) | 1/14 (7.1%) | 1/5 (20%) | 0/16 (0%) | ||||
| Ascites | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Change of bowel habit | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Gastrointestinal pain | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Haemorrhoidal haemorrhage | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Ileus | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Mouth ulceration | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Oral disorder | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Oral pain | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Scalloped tongue | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Small intestinal obstruction | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| General disorders | ||||||||
| Fatigue | 12/15 (80%) | 8/14 (57.1%) | 3/5 (60%) | 14/16 (87.5%) | ||||
| Pyrexia | 12/15 (80%) | 10/14 (71.4%) | 4/5 (80%) | 9/16 (56.3%) | ||||
| Oedema peripheral | 4/15 (26.7%) | 5/14 (35.7%) | 1/5 (20%) | 3/16 (18.8%) | ||||
| Pain | 3/15 (20%) | 2/14 (14.3%) | 2/5 (40%) | 6/16 (37.5%) | ||||
| Chills | 2/15 (13.3%) | 3/14 (21.4%) | 1/5 (20%) | 3/16 (18.8%) | ||||
| Non-cardiac chest pain | 1/15 (6.7%) | 4/14 (28.6%) | 3/5 (60%) | 0/16 (0%) | ||||
| Chest pain | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 4/16 (25%) | ||||
| Asthenia | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 3/16 (18.8%) | ||||
| Injection site reaction | 2/15 (13.3%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Chest discomfort | 0/15 (0%) | 1/14 (7.1%) | 1/5 (20%) | 0/16 (0%) | ||||
| Influenza like illness | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 2/16 (12.5%) | ||||
| Malaise | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Mucosal inflammation | 0/15 (0%) | 1/14 (7.1%) | 1/5 (20%) | 0/16 (0%) | ||||
| Multiple organ dysfunction syndrome | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Peripheral swelling | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Tenderness | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Catheter site bruise | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Catheter site irritation | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Catheter site pain | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Catheter site vesicles | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Face oedema | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Facial pain | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Gait disturbance | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Generalised oedema | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Infusion site extravasation | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Localised oedema | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Oedema | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Hyperbilirubinaemia | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 2/16 (12.5%) | ||||
| Immune system disorders | ||||||||
| Cytokine release syndrome | 4/15 (26.7%) | 5/14 (35.7%) | 3/5 (60%) | 4/16 (25%) | ||||
| Hypersensitivity | 0/15 (0%) | 3/14 (21.4%) | 0/5 (0%) | 0/16 (0%) | ||||
| Drug hypersensitivity | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Seasonal allergy | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Infections and infestations | ||||||||
| Upper respiratory tract infection | 4/15 (26.7%) | 1/14 (7.1%) | 2/5 (40%) | 1/16 (6.3%) | ||||
| Pneumonia | 2/15 (13.3%) | 1/14 (7.1%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Urinary tract infection | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 2/16 (12.5%) | ||||
| Device related infection | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 1/16 (6.3%) | ||||
| Folliculitis | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Abscess | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Acute sinusitis | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Beta haemolytic streptococcal infection | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Bronchitis | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Clostridium difficile colitis | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Cytomegalovirus infection | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Diverticulitis | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Eye infection | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Groin infection | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Herpes zoster | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Lung infection | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Nasopharyngitis | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Oral candidiasis | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Paronychia | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Pseudomonas infection | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Rhinitis | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Rhinovirus infection | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Sinusitis | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Staphylococcal infection | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Streptococcal bacteraemia | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Vaginal infection | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Viral infection | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Contusion | 1/15 (6.7%) | 1/14 (7.1%) | 1/5 (20%) | 0/16 (0%) | ||||
| Fall | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Incision site pain | 1/15 (6.7%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Transfusion reaction | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Infusion related reaction | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Limb injury | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Procedural pain | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Skin abrasion | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Investigations | ||||||||
| White blood cell count decreased | 12/15 (80%) | 10/14 (71.4%) | 5/5 (100%) | 12/16 (75%) | ||||
| Lymphocyte count decreased | 13/15 (86.7%) | 8/14 (57.1%) | 3/5 (60%) | 7/16 (43.8%) | ||||
| Neutrophil count decreased | 11/15 (73.3%) | 8/14 (57.1%) | 4/5 (80%) | 7/16 (43.8%) | ||||
| Platelet count decreased | 12/15 (80%) | 7/14 (50%) | 4/5 (80%) | 7/16 (43.8%) | ||||
| Alanine aminotransferase increased | 6/15 (40%) | 4/14 (28.6%) | 3/5 (60%) | 4/16 (25%) | ||||
| Blood creatinine increased | 8/15 (53.3%) | 2/14 (14.3%) | 1/5 (20%) | 4/16 (25%) | ||||
| Activated partial thromboplastin time prolonged | 9/15 (60%) | 3/14 (21.4%) | 2/5 (40%) | 0/16 (0%) | ||||
| Aspartate aminotransferase increased | 7/15 (46.7%) | 4/14 (28.6%) | 2/5 (40%) | 1/16 (6.3%) | ||||
| Blood alkaline phosphatase increased | 7/15 (46.7%) | 1/14 (7.1%) | 2/5 (40%) | 2/16 (12.5%) | ||||
| Weight decreased | 2/15 (13.3%) | 4/14 (28.6%) | 2/5 (40%) | 2/16 (12.5%) | ||||
| Lipase increased | 6/15 (40%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Amylase increased | 2/15 (13.3%) | 1/14 (7.1%) | 1/5 (20%) | 0/16 (0%) | ||||
| Blood bilirubin increased | 2/15 (13.3%) | 1/14 (7.1%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Blood creatine phosphokinase increased | 1/15 (6.7%) | 0/14 (0%) | 2/5 (40%) | 1/16 (6.3%) | ||||
| Breath sounds abnormal | 0/15 (0%) | 2/14 (14.3%) | 1/5 (20%) | 1/16 (6.3%) | ||||
| C-reactive protein increased | 0/15 (0%) | 1/14 (7.1%) | 2/5 (40%) | 0/16 (0%) | ||||
| Ejection fraction decreased | 0/15 (0%) | 0/14 (0%) | 2/5 (40%) | 0/16 (0%) | ||||
| Haemoglobin decreased | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 2/16 (12.5%) | ||||
| International normalised ratio increased | 2/15 (13.3%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Serum ferritin increased | 0/15 (0%) | 1/14 (7.1%) | 1/5 (20%) | 0/16 (0%) | ||||
| Urine output decreased | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Blood pressure diastolic increased | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Cytomegalovirus test positive | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Electrocardiogram QT prolonged | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Electrocardiogram abnormal | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Epstein-Barr virus antibody positive | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Transaminases increased | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| White blood cells urine positive | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Hypophosphataemia | 9/15 (60%) | 7/14 (50%) | 3/5 (60%) | 6/16 (37.5%) | ||||
| Hyponatraemia | 11/15 (73.3%) | 7/14 (50%) | 2/5 (40%) | 2/16 (12.5%) | ||||
| Decreased appetite | 5/15 (33.3%) | 5/14 (35.7%) | 2/5 (40%) | 7/16 (43.8%) | ||||
| Hypoalbuminaemia | 10/15 (66.7%) | 4/14 (28.6%) | 2/5 (40%) | 2/16 (12.5%) | ||||
| Hypokalaemia | 5/15 (33.3%) | 6/14 (42.9%) | 1/5 (20%) | 6/16 (37.5%) | ||||
| Hypocalcaemia | 8/15 (53.3%) | 4/14 (28.6%) | 2/5 (40%) | 2/16 (12.5%) | ||||
| Hypomagnesaemia | 6/15 (40%) | 1/14 (7.1%) | 0/5 (0%) | 5/16 (31.3%) | ||||
| Dehydration | 3/15 (20%) | 2/14 (14.3%) | 1/5 (20%) | 1/16 (6.3%) | ||||
| Hyperglycaemia | 3/15 (20%) | 2/14 (14.3%) | 0/5 (0%) | 2/16 (12.5%) | ||||
| Hyperkalaemia | 4/15 (26.7%) | 0/14 (0%) | 1/5 (20%) | 1/16 (6.3%) | ||||
| Hypermagnesaemia | 1/15 (6.7%) | 2/14 (14.3%) | 1/5 (20%) | 1/16 (6.3%) | ||||
| Appetite disorder | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Hyperchloraemia | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Hyperphosphataemia | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Hyperuricaemia | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Hypoglycaemia | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Lactic acidosis | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Metabolic acidosis | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Vitamin D deficiency | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Musculoskeletal chest pain | 8/15 (53.3%) | 2/14 (14.3%) | 0/5 (0%) | 5/16 (31.3%) | ||||
| Pain in extremity | 7/15 (46.7%) | 2/14 (14.3%) | 2/5 (40%) | 4/16 (25%) | ||||
| Back pain | 3/15 (20%) | 4/14 (28.6%) | 2/5 (40%) | 5/16 (31.3%) | ||||
| Myalgia | 5/15 (33.3%) | 2/14 (14.3%) | 1/5 (20%) | 5/16 (31.3%) | ||||
| Arthralgia | 4/15 (26.7%) | 2/14 (14.3%) | 1/5 (20%) | 4/16 (25%) | ||||
| Musculoskeletal pain | 4/15 (26.7%) | 2/14 (14.3%) | 1/5 (20%) | 2/16 (12.5%) | ||||
| Neck pain | 2/15 (13.3%) | 1/14 (7.1%) | 1/5 (20%) | 3/16 (18.8%) | ||||
| Bone pain | 1/15 (6.7%) | 2/14 (14.3%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Flank pain | 0/15 (0%) | 3/14 (21.4%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Muscular weakness | 2/15 (13.3%) | 0/14 (0%) | 0/5 (0%) | 2/16 (12.5%) | ||||
| Muscle spasms | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 2/16 (12.5%) | ||||
| Pain in jaw | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 2/16 (12.5%) | ||||
| Joint range of motion decreased | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Limb discomfort | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Mobility decreased | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Musculoskeletal discomfort | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Trismus | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Tumour pain | 2/15 (13.3%) | 2/14 (14.3%) | 0/5 (0%) | 2/16 (12.5%) | ||||
| Infected neoplasm | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Neoplasm skin | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 9/15 (60%) | 3/14 (21.4%) | 3/5 (60%) | 4/16 (25%) | ||||
| Headache | 8/15 (53.3%) | 1/14 (7.1%) | 3/5 (60%) | 7/16 (43.8%) | ||||
| Paraesthesia | 4/15 (26.7%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Peripheral sensory neuropathy | 2/15 (13.3%) | 1/14 (7.1%) | 1/5 (20%) | 0/16 (0%) | ||||
| Dysgeusia | 2/15 (13.3%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Neuralgia | 2/15 (13.3%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Disturbance in attention | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Lethargy | 0/15 (0%) | 1/14 (7.1%) | 1/5 (20%) | 0/16 (0%) | ||||
| Migraine | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Peripheral motor neuropathy | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Presyncope | 0/15 (0%) | 0/14 (0%) | 2/5 (40%) | 0/16 (0%) | ||||
| Dysarthria | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Memory impairment | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Neuropathy peripheral | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Neurotoxicity | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Peripheral sensorimotor neuropathy | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Phantom limb syndrome | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Somnolence | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Tremor | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Psychiatric disorders | ||||||||
| Anxiety | 10/15 (66.7%) | 3/14 (21.4%) | 0/5 (0%) | 6/16 (37.5%) | ||||
| Insomnia | 4/15 (26.7%) | 5/14 (35.7%) | 0/5 (0%) | 3/16 (18.8%) | ||||
| Depression | 3/15 (20%) | 1/14 (7.1%) | 1/5 (20%) | 1/16 (6.3%) | ||||
| Confusional state | 1/15 (6.7%) | 3/14 (21.4%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Agitation | 1/15 (6.7%) | 2/14 (14.3%) | 1/5 (20%) | 0/16 (0%) | ||||
| Mental status changes | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Paranoia | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Restlessness | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Sleep disorder | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Social avoidant behaviour | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Suicidal ideation | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Proteinuria | 1/15 (6.7%) | 2/14 (14.3%) | 2/5 (40%) | 1/16 (6.3%) | ||||
| Haematuria | 1/15 (6.7%) | 3/14 (21.4%) | 0/5 (0%) | 0/16 (0%) | ||||
| Acute kidney injury | 0/15 (0%) | 2/14 (14.3%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Urinary tract pain | 1/15 (6.7%) | 2/14 (14.3%) | 0/5 (0%) | 0/16 (0%) | ||||
| Dysuria | 0/15 (0%) | 2/14 (14.3%) | 0/5 (0%) | 0/16 (0%) | ||||
| Haemoglobinuria | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Pollakiuria | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Anuria | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Chromaturia | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Chronic kidney disease | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Fanconi syndrome acquired | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Glycosuria | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Micturition urgency | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Oliguria | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Renal tubular acidosis | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Urinary retention | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Premature menopause | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Genital rash | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Menorrhagia | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Menstruation irregular | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Oedema genital | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Pelvic pain | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Pruritus genital | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Vaginal discharge | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Vaginal haemorrhage | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Vulvovaginal dryness | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnoea | 8/15 (53.3%) | 10/14 (71.4%) | 3/5 (60%) | 7/16 (43.8%) | ||||
| Cough | 9/15 (60%) | 6/14 (42.9%) | 3/5 (60%) | 3/16 (18.8%) | ||||
| Hypoxia | 2/15 (13.3%) | 3/14 (21.4%) | 3/5 (60%) | 2/16 (12.5%) | ||||
| Nasal congestion | 6/15 (40%) | 0/14 (0%) | 2/5 (40%) | 2/16 (12.5%) | ||||
| Pleural effusion | 3/15 (20%) | 4/14 (28.6%) | 2/5 (40%) | 1/16 (6.3%) | ||||
| Tachypnoea | 1/15 (6.7%) | 4/14 (28.6%) | 3/5 (60%) | 0/16 (0%) | ||||
| Oropharyngeal pain | 3/15 (20%) | 1/14 (7.1%) | 2/5 (40%) | 1/16 (6.3%) | ||||
| Pleuritic pain | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 2/16 (12.5%) | ||||
| Dysphonia | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Productive cough | 3/15 (20%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Rhinitis allergic | 3/15 (20%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Rhinorrhoea | 1/15 (6.7%) | 1/14 (7.1%) | 1/5 (20%) | 0/16 (0%) | ||||
| Throat irritation | 0/15 (0%) | 2/14 (14.3%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Atelectasis | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Dyspnoea exertional | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Epistaxis | 2/15 (13.3%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Haemoptysis | 1/15 (6.7%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Pulmonary embolism | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 2/16 (12.5%) | ||||
| Wheezing | 0/15 (0%) | 1/14 (7.1%) | 1/5 (20%) | 0/16 (0%) | ||||
| Aspiration | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Hiccups | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Hypopnoea | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Laryngeal haemorrhage | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Nasal dryness | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Pneumonitis | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Pneumothorax | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Pulmonary haemorrhage | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Pulmonary oedema | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Pruritus | 6/15 (40%) | 4/14 (28.6%) | 1/5 (20%) | 2/16 (12.5%) | ||||
| Rash maculo-papular | 7/15 (46.7%) | 4/14 (28.6%) | 1/5 (20%) | 1/16 (6.3%) | ||||
| Alopecia | 1/15 (6.7%) | 3/14 (21.4%) | 3/5 (60%) | 3/16 (18.8%) | ||||
| Rash | 2/15 (13.3%) | 3/14 (21.4%) | 1/5 (20%) | 1/16 (6.3%) | ||||
| Dry skin | 2/15 (13.3%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Erythema | 0/15 (0%) | 2/14 (14.3%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Skin hyperpigmentation | 1/15 (6.7%) | 1/14 (7.1%) | 1/5 (20%) | 0/16 (0%) | ||||
| Acne | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 1/16 (6.3%) | ||||
| Dermatitis acneiform | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 1/16 (6.3%) | ||||
| Dermatitis exfoliative generalised | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Hyperhidrosis | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Night sweats | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 2/16 (12.5%) | ||||
| Pain of skin | 2/15 (13.3%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Skin exfoliation | 0/15 (0%) | 1/14 (7.1%) | 1/5 (20%) | 0/16 (0%) | ||||
| Angioedema | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Cold sweat | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Dermatitis | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Ecchymosis | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Nail disorder | 0/15 (0%) | 0/14 (0%) | 0/5 (0%) | 1/16 (6.3%) | ||||
| Onychomadesis | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 0/16 (0%) | ||||
| Petechiae | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Purpura | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Rash erythematous | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Rash macular | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Rash papular | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Skin discolouration | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Skin ulcer | 1/15 (6.7%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Subcutaneous emphysema | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Vascular disorders | ||||||||
| Hypotension | 4/15 (26.7%) | 8/14 (57.1%) | 2/5 (40%) | 7/16 (43.8%) | ||||
| Hypertension | 2/15 (13.3%) | 3/14 (21.4%) | 2/5 (40%) | 5/16 (31.3%) | ||||
| Hot flush | 3/15 (20%) | 0/14 (0%) | 0/5 (0%) | 0/16 (0%) | ||||
| Embolism | 0/15 (0%) | 1/14 (7.1%) | 1/5 (20%) | 0/16 (0%) | ||||
| Flushing | 1/15 (6.7%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Pallor | 0/15 (0%) | 0/14 (0%) | 1/5 (20%) | 1/16 (6.3%) | ||||
| Deep vein thrombosis | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
| Vena cava thrombosis | 0/15 (0%) | 1/14 (7.1%) | 0/5 (0%) | 0/16 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | GSK Response Center |
|---|---|
| Organization | GlaxoSmithKline |
| Phone | 866-435-7343 |
| GSKClinicalSupportHD@gsk.com |
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01343043
Other Study ID Numbers:
- 208466
- ADP 04511
- 2015-005594-21
First Posted:
Apr 27, 2011
Last Update Posted:
Jun 30, 2021
Last Verified:
Jun 1, 2021