Study of NY-ESO-1 ISCOMATRIX® in Patients With Measurable Stage III or IV Melanoma

• Sponsor: Ludwig Institute for Cancer Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT00518206
• Collaborator: Austin Health (Other), Peter MacCallum Cancer Institute (Other)
• Enrollment: 46
• Locations: 2
• Arms: 2
• Actual Duration (Months): 73.8
• Patients Per Site: 23
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This was a Phase 2, open-label study of the NY-ESO-1 ISCOMATRIX® (ISCOM) vaccine administered as an intramuscular injection given every 4 weeks to subjects with measurable advanced malignant melanoma. Study objectives included determination of the anticancer activity, cellular and humoral immunogenicity, and safety and tolerability of the NY-ESO-1 ISCOM vaccine administered alone or preceded by a single administration of low-dose cyclophosphamide.

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Biological: NY-ESO-1 ISCOMATRIX® vaccine; Drug: Cyclophosphamide	Phase 2

Detailed Description

In Cohort 1, 6 subjects were initially vaccinated with the NY-ESO-1 ISCOM vaccine at a dose of 100 µg of the NY-ESO-1 protein + 120 µg of the ISCOM adjuvant. These 6 subjects were monitored for dose-limiting toxicity (DLT) for 7 days after the first vaccination. Upon observation of tolerability (ie, < 2/6 subjects with DLT), enrollment proceeded to a total accrual of approximately 25 subjects. Subjects received 3 vaccinations administered every 4 weeks (ie, weeks 1, 5, and 9) followed by immunological and clinical response evaluations, with clinical responses categorized according to the Response Evaluation Criteria in Solid Tumors (RECIST). In the absence of disease progression, subjects may have received 3 additional vaccinations administered every 4 weeks, followed by additional vaccinations administered every 12 weeks thereafter until development of disease progression or other criteria for discontinuation.

In Cohort 2, subjects received the NY-ESO-1 ISCOM vaccine on the same schedule as described for Cohort 1, but Cohort 2 subjects also received a single intravenous infusion of low-dose cyclophosphamide 1 day prior to each NY-ESO-1 ISCOM vaccination. If responses were observed in 2 of 16 subjects initially treated in Cohort 2, then 9 additional subjects were to be accrued to Cohort 2, for a total potential accrual of 25 subjects.

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Cohort 1 was enrolled first, in which subjects received the NY-ESO-1 ISCOM vaccine. Enrollment then proceeded to Cohort 2, in which subjects received the NY-ESO-1 ISCOM vaccine and low-dose cyclophosphamide.Cohort 1 was enrolled first, in which subjects received the NY-ESO-1 ISCOM vaccine. Enrollment then proceeded to Cohort 2, in which subjects received the NY-ESO-1 ISCOM vaccine and low-dose cyclophosphamide.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of the Clinical and Immunological Effects of NY-ESO-1 ISCOM® Vaccine in Patients With Measurable Stage III and IV Malignant Melanoma
• Actual Study Start Date: Nov 28, 2003
• Actual Primary Completion Date: Jan 22, 2010
• Actual Study Completion Date: Jan 22, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 NY-ESO-1 ISCOM vaccine (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant) administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.	Biological: NY-ESO-1 ISCOMATRIX® vaccine; NY-ESO-1 ISCOM vaccine (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant) administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.
Experimental: Cohort 2 Cyclophosphamide (300 mg/m^2) administered as an intravenous injection 1 day prior to each vaccination with NY-ESO-1 ISCOM (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant), which was administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.	Biological: NY-ESO-1 ISCOMATRIX® vaccine; NY-ESO-1 ISCOM vaccine (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant) administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.; Drug: Cyclophosphamide; Cyclophosphamide (300 mg/m^2) administered as an intravenous injection 1 day prior to each vaccination with NY-ESO-1 ISCOM (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant), which was administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Best Overall Tumor Response [Up to 22 months]

   Tumor responses were evaluated using computed tomography and categorized according to RECIST (version 1.0) at baseline, at week 11, between weeks 23 and 25, and every 12 weeks thereafter. Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions [no evidence of disease]; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.

Secondary Outcome Measures

1. Cellular Immunogenicity of the NY-ESO-1 ISCOM Vaccine [Up to 22 months]

   Blood samples were drawn to measure cellular response at pretreatment and weeks 3, 7, 11, between weeks 23 and 25, week 33, and every 12 weeks thereafter. Cellular immunity included an assay for gamma interferon-producing T cells and enumeration of NY-ESO-1b-specific T cells, detected by fluorescent labeled human leukocyte antigen (HLA)-A2 tetramers carrying the NY-ESO-1b peptide, expressed as percent positive staining of CD4+ and CD8+ T cells. Data are presented for CD4+ and CD8+ T-cell responses (not mutually exclusive) that were pre-existing at baseline (BL) or presented at any time post-BL.

2. Post-Vaccination Delayed-type Hypersensitivity (DTH) Reactions [Up to 22 months]

   NY-ESO-1-specific DTH was measured by intradermal injection with the full-length NY-ESO-1 protein, NY-ESO-1b peptide, and NY-ESO-1 DP4 peptide at pretreatment, week 11, and between week 23 and 25. DTH reactions (eg, local skin irritation) were evaluated 2 days after DTH injections. Data presented are based on injections with the full-length peptide, as these data are considered to be representative of the comprehensive DTH results.

3. Humoral Immunogenicity of the NY-ESO-1 ISCOM Vaccine [Up to 22 months]

   Blood samples were drawn to measure humoral immunologic response at pretreatment and weeks 3, 7, 11, 33, and every 12 weeks thereafter. Humoral immunity was assessed by measurement of antibodies to NY-ESO-1 by enzyme-linked immunosorbent assay (ELISA). Data are presented according to baseline (BL) NY-ESO-1 antibody positivity and the time to seroconversion, if applicable.

4. Number of Subjects With Treatment-emergent Adverse Events [Up to 22 months]

   Toxicity was graded in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period. Dose-limiting toxicity was defined as any treatment-related grade 4 toxicity or any grade 3 toxicity, excluding grade 3 skin necrosis at the site of the delayed-type hypersensitivity reaction, fever, or asymptomatic hyperglycemia that improved to baseline within 3 weeks of onset.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Stage IV (metastatic) or unresectable stage III malignant melanoma.

2. Measurable disease using RECIST.

3. No other effective therapy available or appropriate.

4. Expression of NY-ESO-1 or LAGE-1 by immunohistochemistry (IHC) or reverse transcription-polymerase chain reaction (RT-PCR).

5. Expected survival of at least 4 months.

6. Karnofsky performance status of ≥ 70%.

7. Within 3 weeks prior to first administration of study drug, the following laboratory parameters were required to be within the ranges specified:

• Hemoglobin ≥ 100 g/L

• Platelets ≥ 100 x 10^9/L

• International normalized ratio ≤ 2.0

• Creatinine ≤ 0.2 mmol/L

• Bilirubin ≤ 30 mmol/L

1. Age ≥ 18 years.

2. Able and willing to give written informed consent.

Exclusion Criteria:

1. Other serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders, or any condition that in the opinion of the Investigator would have interfered with the ability of the patient to complete all study requirements.

2. Other malignancy within last 3 years, except for treated melanoma or non-melanoma skin cancer or cervical cancer in situ.

3. Known immunodeficiency.

4. Known human immunodeficiency virus positivity.

5. Concomitant systemic treatment with corticosteroids, anti-histaminic drugs, or nonsteroidal anti-inflammatory drugs. Specific cyclooxygenase-2 (COX-2) inhibitors, low-dose aspirin for the prevention of an acute cardiovascular event, and topical or inhaled steroids were permitted.

6. Chemotherapy and/or radiotherapy within 4 weeks prior to study week 1.

7. Other immunotherapy within 4 weeks prior to study week 1.

8. Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.

9. Lack of availability for immunological and clinical follow-up assessment.

10. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.

11. Pregnancy or breastfeeding.

12. Women of childbearing potential: refusal or inability to use effective means of contraception.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peter MacCallum Cancer Institute	East Melbourne	Victoria	Australia	3002
2	Austin Health (Ludwig Institute Oncology Unit)	Heidelberg	Victoria	Australia	3084

Sponsors and Collaborators

• Ludwig Institute for Cancer Research
• Austin Health
• Peter MacCallum Cancer Institute

Investigators

• Principal Investigator: Jonathan S Cebon, FRACP, MBBS, PhD, Ludwig Institute for Cancer Research - Oncology Unit
• Principal Investigator: Ian D Davis, FRACP, FAChPM, MBBS, PhD, Ludwig Institute for Cancer Research - Oncology Unit

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ludwig Institute for Cancer Research
• ClinicalTrials.gov Identifier: NCT00518206
• Other Study ID Numbers: LUD2002-013; CTN Trial No.: 2007/123; CTN-Protocol# LUD2002-013AMEND
• First Posted: Aug 20, 2007
• Last Update Posted: Aug 14, 2017
• Last Verified: Jun 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Ludwig Institute for Cancer Research: Clinical Trial; Phase 2; Cancer Vaccine; NY-ESO-1 protein, human; ISCOMATRIX, immunological adjuvant; Cyclophosphamide; T-Cells, Regulatory
• Additional relevant MeSH terms: Melanoma; Cyclophosphamide

Study Results

Participant Flow

Arm/Group Title	Cohort 1: NY-ESO-1 ISCOM	Cohort 2: Cyclophosphamide + NY-ESO-1 ISCOM
Arm/Group Description	Subjects received the NY-ESO-1 ISCOM vaccine (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant) administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.	Subjects received cyclophosphamide (300 mg/m^2) administered as an intravenous injection 1 day prior to each vaccination with NY-ESO-1 ISCOM (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant), which was administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.
Period Title: Overall Study
STARTED	27	19
COMPLETED	16	13
NOT COMPLETED	11	6

Baseline Characteristics

Arm/Group Title	Cohort 1: NY-ESO-1 ISCOM	Cohort 2: Cyclophosphamide + NY-ESO-1 ISCOM	Total
Arm/Group Description	Subjects received the NY-ESO-1 ISCOM vaccine (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant) administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.	Subjects received cyclophosphamide (300 mg/m^2) administered as an intravenous injection 1 day prior to each vaccination with NY-ESO-1 ISCOM (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant), which was administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.	Total of all reporting groups
Overall Participants	27	19	46
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61.0	61.0	61.0
Sex: Female, Male (Count of Participants)
Female	13 48.1%	7 36.8%	20 43.5%
Male	14 51.9%	12 63.2%	26 56.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	0 0%	0 0%	0 0%
Unknown or Not Reported	27 100%	19 100%	46 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	1 3.7%	0 0%	1 2.2%
Black or African American	0 0%	0 0%	0 0%
White	26 96.3%	13 68.4%	39 84.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	6 31.6%	6 13%
Region of Enrollment (Count of Participants)
Australia	27 100%	19 100%	46 100%
Karnofsky Performance Status (Count of Participants)
70	2 7.4%	0 0%	2 4.3%
80	3 11.1%	1 5.3%	4 8.7%
90	4 14.8%	8 42.1%	12 26.1%
100	18 66.7%	10 52.6%	28 60.9%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Best Overall Tumor Response
Description	Tumor responses were evaluated using computed tomography and categorized according to RECIST (version 1.0) at baseline, at week 11, between weeks 23 and 25, and every 12 weeks thereafter. Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions [no evidence of disease]; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.
Time Frame	Up to 22 months

Outcome Measure Data

Analysis Population Description

Subjects with data available from at least 1 post-baseline response assessment.

Arm/Group Title	Cohort 1: NY-ESO-1 ISCOM	Cohort 2: Cyclophosphamide + NY-ESO-1 ISCOM
Arm/Group Description	Subjects received the NY-ESO-1 ISCOM vaccine (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant) administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.	Subjects received cyclophosphamide (300 mg/m^2) administered as an intravenous injection 1 day prior to each vaccination with NY-ESO-1 ISCOM (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant), which was administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.
Measure Participants	25	19
Partial response	1 3.7%	1 5.3%
Stable disease	12 44.4%	4 21.1%
Progressive disease	12 44.4%	14 73.7%

2. Secondary Outcome

Title	Cellular Immunogenicity of the NY-ESO-1 ISCOM Vaccine
Description	Blood samples were drawn to measure cellular response at pretreatment and weeks 3, 7, 11, between weeks 23 and 25, week 33, and every 12 weeks thereafter. Cellular immunity included an assay for gamma interferon-producing T cells and enumeration of NY-ESO-1b-specific T cells, detected by fluorescent labeled human leukocyte antigen (HLA)-A2 tetramers carrying the NY-ESO-1b peptide, expressed as percent positive staining of CD4+ and CD8+ T cells. Data are presented for CD4+ and CD8+ T-cell responses (not mutually exclusive) that were pre-existing at baseline (BL) or presented at any time post-BL.
Time Frame	Up to 22 months

Outcome Measure Data

Analysis Population Description

Subjects with available results from the evaluation of T-cell responses in peripheral blood.

Arm/Group Title	Cohort 1: NY-ESO-1 ISCOM	Cohort 2: Cyclophosphamide + NY-ESO-1 ISCOM
Arm/Group Description	Subjects received the NY-ESO-1 ISCOM vaccine (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant) administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.	Subjects received cyclophosphamide (300 mg/m^2) administered as an intravenous injection 1 day prior to each vaccination with NY-ESO-1 ISCOM (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant), which was administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.
Measure Participants	25	14
CD4+ T-cell Response at BL and Post-BL	4 14.8%	3 15.8%
New CD4+ T-cell Response Post-BL	6 22.2%	7 36.8%
CD8+ T-cell Response at BL and Post-BL	12 44.4%	3 15.8%
New CD8+ T-cell Response Post-BL	5 18.5%	1 5.3%
No CD4+ or CD8+ T-cell Response	6 22.2%	3 15.8%

3. Secondary Outcome

Title	Post-Vaccination Delayed-type Hypersensitivity (DTH) Reactions
Description	NY-ESO-1-specific DTH was measured by intradermal injection with the full-length NY-ESO-1 protein, NY-ESO-1b peptide, and NY-ESO-1 DP4 peptide at pretreatment, week 11, and between week 23 and 25. DTH reactions (eg, local skin irritation) were evaluated 2 days after DTH injections. Data presented are based on injections with the full-length peptide, as these data are considered to be representative of the comprehensive DTH results.
Time Frame	Up to 22 months

Outcome Measure Data

Analysis Population Description

Subjects who underwent DTH testing with available DTH reaction evaluation(s).

Arm/Group Title	Cohort 1: NY-ESO-1 ISCOM	Cohort 2: Cyclophosphamide + NY-ESO-1 ISCOM
Arm/Group Description	Subjects received the NY-ESO-1 ISCOM vaccine (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant) administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.	Subjects received cyclophosphamide (300 mg/m^2) administered as an intravenous injection 1 day prior to each vaccination with NY-ESO-1 ISCOM (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant), which was administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.
Measure Participants	25	19
Reaction at Pretreatment and Week 11	2 7.4%	3 15.8%
Reaction at Pretreatment and Week 23	1 3.7%	0 0%
Reaction at Pretreatment, No Reaction On Study	0 0%	1 5.3%
Reaction at Pretreatment, No On Study DTH Results	0 0%	1 5.3%
No Reaction Pretreatment , Reaction at Week 11	6 22.2%	4 21.1%
No Reaction Pretreatment , Reaction at Week 23	0 0%	3 15.8%
No Reaction Pretreatment or on Study	16 59.3%	6 31.6%
No Reaction Pretreatment, No On Study DTH Results	0 0%	3 15.8%

4. Secondary Outcome

Title	Humoral Immunogenicity of the NY-ESO-1 ISCOM Vaccine
Description	Blood samples were drawn to measure humoral immunologic response at pretreatment and weeks 3, 7, 11, 33, and every 12 weeks thereafter. Humoral immunity was assessed by measurement of antibodies to NY-ESO-1 by enzyme-linked immunosorbent assay (ELISA). Data are presented according to baseline (BL) NY-ESO-1 antibody positivity and the time to seroconversion, if applicable.
Time Frame	Up to 22 months

Outcome Measure Data

Analysis Population Description

Subjects with available measurement of baseline and post-baseline positivity for NY-ESO-1 antibodies.

Arm/Group Title	Cohort 1: NY-ESO-1 ISCOM	Cohort 2: Cyclophosphamide + NY-ESO-1 ISCOM
Arm/Group Description	Subjects received the NY-ESO-1 ISCOM vaccine (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant) administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.	Subjects received cyclophosphamide (300 mg/m^2) administered as an intravenous injection 1 day prior to each vaccination with NY-ESO-1 ISCOM (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant), which was administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.
Measure Participants	27	15
NY-ESO-1 (+) at BL and Post-BL	7 25.9%	2 10.5%
NY-ESO-1 (-) at BL, converted to (+) Post-BL	19 70.4%	8 42.1%
NY-ESO-1 (-) at BL and Post-BL	1 3.7%	5 26.3%

5. Secondary Outcome

Title	Number of Subjects With Treatment-emergent Adverse Events
Description	Toxicity was graded in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period. Dose-limiting toxicity was defined as any treatment-related grade 4 toxicity or any grade 3 toxicity, excluding grade 3 skin necrosis at the site of the delayed-type hypersensitivity reaction, fever, or asymptomatic hyperglycemia that improved to baseline within 3 weeks of onset.
Time Frame	Up to 22 months

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set comprises all subjects who received at least 1 dose of study drug.

Arm/Group Title	Cohort 1: NY-ESO-1 ISCOM	Cohort 2: Cyclophosphamide + NY-ESO-1 ISCOM
Arm/Group Description	Subjects received the NY-ESO-1 ISCOM vaccine (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant) administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.	Subjects received cyclophosphamide (300 mg/m^2) administered as an intravenous injection 1 day prior to each vaccination with NY-ESO-1 ISCOM (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant), which was administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.
Measure Participants	27	19
Any TEAE	27 100%	19 100%
Maximum Grade 3 TEAE	4 14.8%	9 47.4%
Maximum Grade 4 TEAE	1 3.7%	1 5.3%
Treatment-related TEAE	26 96.3%	19 100%
Serious TEAE	5 18.5%	7 36.8%
Death	0 0%	0 0%
TEAE Leading to Discontinuation	2 7.4%	1 5.3%
Dose-limiting Toxicity	0 0%	0 0%

Adverse Events

Time Frame	All adverse events (AEs) occurring between the signing of informed consent and the off-study date were documented, regardless of the causal relationship to study drug. AEs occurring after the first dose of study drug were considered treatment emergent (i.e., TEAEs). The AE reporting period for this study was up to 22 months.
Adverse Event Reporting Description	AE documentation included onset/resolution dates, severity using the NCI CTCAE (version 3.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per subject at the maximum reported grade.
Arm/Group Title	Cohort 1: NY-ESO-1 ISCOM		Cohort 2: Cyclophosphamide + NY-ESO-1 ISCOM
Arm/Group Description	Subjects received the NY-ESO-1 ISCOM vaccine (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant) administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.		Subjects received cyclophosphamide (300 mg/m^2) administered as an intravenous injection 1 day prior to each vaccination with NY-ESO-1 ISCOM (100 μg of the NY-ESO-1 protein formulated with 120 μg of ISCOM adjuvant), which was administered as an intramuscular injection every 4 weeks for 3 doses in every cycle.
All Cause Mortality
	Cohort 1: NY-ESO-1 ISCOM		Cohort 2: Cyclophosphamide + NY-ESO-1 ISCOM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/19 (0%)
Serious Adverse Events
	Cohort 1: NY-ESO-1 ISCOM		Cohort 2: Cyclophosphamide + NY-ESO-1 ISCOM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/27 (18.5%)		7/19 (36.8%)
Blood and lymphatic system disorders
Anaemia	1/27 (3.7%)		0/19 (0%)
Gastrointestinal disorders
Abdominal pain	1/27 (3.7%)		1/19 (5.3%)
General disorders
Oedema peripheral	1/27 (3.7%)		0/19 (0%)
Chest pain	1/27 (3.7%)		1/19 (5.3%)
Fatigue	1/27 (3.7%)		0/19 (0%)
Infections and infestations
Bronchopneumonia	0/27 (0%)		1/19 (5.3%)
Appendicitis	0/27 (0%)		1/19 (5.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/27 (3.7%)		0/19 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant breast lump removal	1/27 (3.7%)		0/19 (0%)
Metastatic malignant melanoma	0/27 (0%)		1/19 (5.3%)
Metastases to central nervous system	0/27 (0%)		2/19 (10.5%)
Nervous system disorders
Neuralgia	0/27 (0%)		1/19 (5.3%)
Headache	0/27 (0%)		1/19 (5.3%)
Renal and urinary disorders
Urinary retention	1/27 (3.7%)		0/19 (0%)
Haematuria	1/27 (3.7%)		0/19 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/27 (3.7%)		0/19 (0%)
Vascular disorders
Aortic stenosis	0/27 (0%)		1/19 (5.3%)
Other (Not Including Serious) Adverse Events
	Cohort 1: NY-ESO-1 ISCOM		Cohort 2: Cyclophosphamide + NY-ESO-1 ISCOM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/27 (100%)		19/19 (100%)
Blood and lymphatic system disorders
Anaemia	1/27 (3.7%)		2/19 (10.5%)
Leukopenia	0/27 (0%)		1/19 (5.3%)
Thrombocytosis	0/27 (0%)		1/19 (5.3%)
Cardiac disorders
Palpitations	0/27 (0%)		1/19 (5.3%)
Eye disorders
Eyelid ptosis	0/27 (0%)		1/19 (5.3%)
Gastrointestinal disorders
Abdominal pain	3/27 (11.1%)		2/19 (10.5%)
Abdominal pain upper	2/27 (7.4%)		1/19 (5.3%)
Diarrhoea	2/27 (7.4%)		4/19 (21.1%)
Nausea	4/27 (14.8%)		13/19 (68.4%)
Vomiting	5/27 (18.5%)		2/19 (10.5%)
Constipation	1/27 (3.7%)		8/19 (42.1%)
Abdominal pain lower	0/27 (0%)		3/19 (15.8%)
Abdominal discomfort	0/27 (0%)		1/19 (5.3%)
Abdominal mass	1/27 (3.7%)		1/19 (5.3%)
Abdominal wall mass	0/27 (0%)		1/19 (5.3%)
Dry mouth	0/27 (0%)		1/19 (5.3%)
Dyspepsia	0/27 (0%)		1/19 (5.3%)
General disorders
Axilliary pain	3/27 (11.1%)		0/19 (0%)
Chills	2/27 (7.4%)		1/19 (5.3%)
Fatigue	10/27 (37%)		13/19 (68.4%)
Influenza like illness	6/27 (22.2%)		1/19 (5.3%)
Injection site erythema	5/27 (18.5%)		1/19 (5.3%)
Injection site pain	19/27 (70.4%)		16/19 (84.2%)
Pyrexia	3/27 (11.1%)		2/19 (10.5%)
Chest discomfort	0/27 (0%)		1/19 (5.3%)
Feeling hot	0/27 (0%)		1/19 (5.3%)
Pain	1/27 (3.7%)		1/19 (5.3%)
Hepatobiliary disorders
Hepatomegaly	1/27 (3.7%)		1/19 (5.3%)
Infections and infestations
Post procedural infection	2/27 (7.4%)		0/19 (0%)
Upper respiratory tract infection	5/27 (18.5%)		2/19 (10.5%)
Nasopharyngitis	0/27 (0%)		3/19 (15.8%)
Herpes simplex	0/27 (0%)		1/19 (5.3%)
Lower respiratory tract infection	0/27 (0%)		1/19 (5.3%)
Respiratory tract infection	0/27 (0%)		1/19 (5.3%)
Investigations
Lymph node palpable	3/27 (11.1%)		0/19 (0%)
Weight decreased	2/27 (7.4%)		1/19 (5.3%)
Blood creatine increased	0/27 (0%)		1/19 (5.3%)
Blood lactate dehydrogenase increased	0/27 (0%)		1/19 (5.3%)
Metabolism and nutrition disorders
Decreased appetite	4/27 (14.8%)		4/19 (21.1%)
Hypoalbuminaemia	0/27 (0%)		1/19 (5.3%)
Musculoskeletal and connective tissue disorders
Back pain	3/27 (11.1%)		1/19 (5.3%)
Muscle spasms	2/27 (7.4%)		0/19 (0%)
Musculoskeletal chest pain	2/27 (7.4%)		4/19 (21.1%)
Myalgia	5/27 (18.5%)		2/19 (10.5%)
Pain in extremity	6/27 (22.2%)		3/19 (15.8%)
Musculoskeletal pain	1/27 (3.7%)		5/19 (26.3%)
Arthralgia	0/27 (0%)		2/19 (10.5%)
Neck pain	0/27 (0%)		2/19 (10.5%)
Arthritis	0/27 (0%)		1/19 (5.3%)
Chest wall mass	0/27 (0%)		1/19 (5.3%)
Groin pain	0/27 (0%)		1/19 (5.3%)
Nodule on extremity	0/27 (0%)		1/19 (5.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	0/27 (0%)		2/19 (10.5%)
Basal cell carcinoma	0/27 (0%)		1/19 (5.3%)
Metastases to muscle	0/27 (0%)		1/19 (5.3%)
Metastases to spine	0/27 (0%)		1/19 (5.3%)
Metastasis	0/27 (0%)		1/19 (5.3%)
Metastatic pain	0/27 (0%)		1/19 (5.3%)
Squamous cell carcinoma	0/27 (0%)		1/19 (5.3%)
Tumour pain	0/27 (0%)		1/19 (5.3%)
Nervous system disorders
Dizziness	4/27 (14.8%)		2/19 (10.5%)
Headache	5/27 (18.5%)		0/19 (0%)
Lethargy	11/27 (40.7%)		1/19 (5.3%)
Ataxia	0/27 (0%)		1/19 (5.3%)
Hemisensory neglect	0/27 (0%)		1/19 (5.3%)
Partial seizures	0/27 (0%)		1/19 (5.3%)
Peripheral motor neuropathy	0/27 (0%)		1/19 (5.3%)
Peripheral sensory neuropathy	0/27 (0%)		1/19 (5.3%)
Sinus headache	0/27 (0%)		1/19 (5.3%)
VIIth nerve paralysis	0/27 (0%)		1/19 (5.3%)
Visual field defect	0/27 (0%)		1/19 (5.3%)
Psychiatric disorders
Insomnia	2/27 (7.4%)		2/19 (10.5%)
Agitation	1/27 (3.7%)		1/19 (5.3%)
Renal and urinary disorders
Haematuria	2/27 (7.4%)		0/19 (0%)
Reproductive system and breast disorders
Dysmenorrhoea	0/27 (0%)		1/19 (5.3%)
Ovarian cyst	0/27 (0%)		1/19 (5.3%)
Respiratory, thoracic and mediastinal disorders
Cough	3/27 (11.1%)		0/19 (0%)
Dyspnoea	6/27 (22.2%)		0/19 (0%)
Haemoptysis	2/27 (7.4%)		0/19 (0%)
Nasal congestion	2/27 (7.4%)		0/19 (0%)
Oropharyngeal pain	2/27 (7.4%)		1/19 (5.3%)
Pleuritic pain	2/27 (7.4%)		0/19 (0%)
Productive cough	2/27 (7.4%)		0/19 (0%)
Wheezing	2/27 (7.4%)		0/19 (0%)
Hiccups	0/27 (0%)		1/19 (5.3%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	4/27 (14.8%)		0/19 (0%)
Subcutaneous nodule	2/27 (7.4%)		1/19 (5.3%)
Pain of skin	0/27 (0%)		1/19 (5.3%)
Pruritus	0/27 (0%)		1/19 (5.3%)
Skin irritation	0/27 (0%)		1/19 (5.3%)
Vascular disorders
Flushing	0/27 (0%)		1/19 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.