Study of NY-ESO-1 ISCOMATRIX® in Patients With High-risk, Resected Melanoma

• Sponsor: Ludwig Institute for Cancer Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT00199901
• Collaborator: Institute of Cancer Research, United Kingdom (Other)
• Enrollment: 111
• Locations: 15
• Arms: 2
• Duration (Months): 75
• Patients Per Site: 7.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this trial is to assess whether treatment with NY-ESO-1 ISCOMATRIX® vaccine improves outcomes for people with Malignant Melanoma which has been removed, but is at high risk of relapse.

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

Detailed Description

NY-ESO-1 protein is an immune target found in many cancers including melanoma. ISCOMATRIX® adjuvant enhances immune responses. This trial compares NY-ESO-1 ISCOMATRIX® vaccine with ISCOMATRIX® adjuvant alone to assess whether treatment with NY-ESO-1 ISCOMATRIX® vaccine improves outcomes for participants with Malignant Melanoma which has been removed, but is at high risk of recurrence.

Eligible participants are randomly allocated to a treatment arm. Treatment involves four intramuscular (into a muscle) injections (1 injection every 4 weeks x 3, plus 1 injection at 6 months).

Participants are assessed for recurrence of melanoma, safety and immune responses (by blood test) over the 18 month study period. Off study, their own doctor will follow them for melanoma recurrence and survival.

Study Design

• Study Type: Interventional
• Actual Enrollment: 111 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-blind Phase II Trial of NY-ESO-1 ISCOMATRIX® Vaccine and ISCOMATRIX® Adjuvant Alone in Patients With Resected Stage Ilc, Illb, lIIc, or IV Malignant Melanoma
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Vaccine NY-ESO-1 ISCOMATRIX® vaccine	Biological: NY-ESO-1 ISCOMATRIX®; 100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient will receive four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses will be given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection will be given at month 6 (day 183 ± 3 days).
Placebo Comparator: Adjuvant Alone ISCOMATRIX® adjuvant alone	Biological: ISCOMATRIX® adjuvant; 120 μg of ISCOMATRIX® adjuvant Each patient will receive four intramuscular injections of ISCOMATRIX® adjuvant alone. The first three doses will be given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection will be given at month 6 (day 183 ± 3 days).

Outcome Measures

Primary Outcome Measures

1. Rate of Relapse-free Survival at 18 Months [18 months]

   The number of patients who were alive and relapse free 18 months after starting therapy and the number of patients who relapsed or died within 18 months of starting therapy. Disease was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) as measured by CT. Disease progression or relapse was based on an increase of 20% or more in the sum of the longest diameter of target lesions, the appearance of any new lesion as confirmed by CT scan or death.

Secondary Outcome Measures

1. Number of Patients With Treatment -Emergent Adverse Events (TEAEs) [18 months]

   Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, performance status evaluations, electrocardiograms, magnetic resonance imaging, and any other medically indicated assessments, including subject interviews, from the time informed consent is signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.

2. Relapse-Free Survival During the Entire Period of Observation (up to 6 Years). [through study completion; up to 6 years]

   Disease was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) as measured by CT. Disease progression or relapse was based on an increase of 20% or more in the sum of the longest diameter of target lesions, the appearance of any new lesion as confirmed by CT scan or death.

3. Overall Survival [through study completion; up to 6 years]

   Overall Survival measured during the entire Period of Observation (up to 6years). Overall survival was measured from start of treatment to the last follow-up or death.

4. NY-ESO-1 Antibody Response at Baseline Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response [Baseline]

   NY-ESO-1-specific antibodies were measured by an enzyme-linked immunosorbent assay ( ELISA) method at baseline and on days 71, 197, 365 and end of study. The results are reported as antibodies to NY-ESO-1-specific Total IgG (reciprocal titer) and were scored on a scale of 0-4 with 0 being no or minimal antibody response (reciprocal titer of 0-100) and 4 a strong antibody response (reciprocal titer of >100,000). The number of patients with each antibody response level are tabulated at each timepoint.

5. NY-ESO-1 Antibody Response on Day 71 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response [Day 71]

   NY-ESO-1-specific antibodies were measured by an enzyme-linked immunosorbent assay ( ELISA) method at baseline and on days 71, 197, 365 and end of study. The results are reported as antibodies to NY-ESO-1-specific Total IgG (reciprocal titer) and were scored on a scale of 0-4 with 0 being no or minimal antibody response (reciprocal titer of 0-100) and 4 a strong antibody response (reciprocal titer of >100,000). The number of patients with each antibody response level are tabulated at each timepoint.

6. NY-ESO-1 Antibody Response on Day 197 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response [Day 197]

   NY-ESO-1-specific antibodies were measured by an enzyme-linked immunosorbent assay ( ELISA) method at baseline and on days 71, 197, 365 and end of study. The results are reported as antibodies to NY-ESO-1-specific Total IgG (reciprocal titer) and were scored on a scale of 0-4 with 0 being no or minimal antibody response (reciprocal titer of 0-100) and 4 a strong antibody response (reciprocal titer of >100,000). The number of patients with each antibody response level are tabulated at each timepoint.

7. NY-ESO-1 Antibody Response on Day 365 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response [Day 365]

   NY-ESO-1-specific antibodies were measured by an enzyme-linked immunosorbent assay ( ELISA) method at baseline and on days 71, 197, 365 and end of study. The results are reported as antibodies to NY-ESO-1-specific Total IgG (reciprocal titer) and were scored on a scale of 0-4 with 0 being no or minimal antibody response (reciprocal titer of 0-100) and 4 a strong antibody response (reciprocal titer of >100,000). The number of patients with each antibody response level are tabulated at each timepoint.

8. NY-ESO-1 Antibody Response at End of Study Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response [End of Study (month 18)]

   NY-ESO-1-specific antibodies were measured by an enzyme-linked immunosorbent assay ( ELISA) method at baseline and on days 71, 197, 365 and end of study. The results are reported as antibodies to NY-ESO-1-specific Total IgG (reciprocal titer) and were scored on a scale of 0-4 with 0 being no or minimal antibody response (reciprocal titer of 0-100) and 4 a strong antibody response (reciprocal titer of >100,000). The number of patients with each antibody response level are tabulated at each timepoint.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically proven malignant melanoma.

• Tumor expression of NY-ESO-1 antigen by immunohistochemistry.

• Fully resected AJCC stage IIc, IIIb, IIIc or IV melanoma.

• Within six months of surgery for melanoma.

• Full recovery from surgery.

• No immunotherapy or systemic adjuvant therapy for melanoma since most recent relapse and/or resection. (Previous adjuvant therapy accepted providing patient relapsed and resected after this.)

• Age 18 years or older.

• Able to give written informed consent.

• Vital laboratory parameters within normal range, or protocol specified ranges.

Exclusion Criteria:

• Other serious or significant illnesses.

• Resected cerebral metastases.

• Ocular melanoma.

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

• Using immunosuppressive drugs.

• Anticoagulation.

• Known HIV positivity.

• Chemotherapy or radiation therapy in last four weeks (6 weeks for nitrosourea drugs).

• Not available for immunological and clinical follow-up assessments.

• Participation in prior clinical trial involving an investigational agent within last 4 weeks.

• Previous isolated limb perfusion (ILP).

• Pregnancy or breastfeeding.

• Refusal or inability to use effective means of contraception for women of childbearing potential.

• Mental impairment that may compromise ability to give informed consent and to comply with study requirements.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sydney Melanoma Unit - Royal Prince Alfred Hospital	Camperdown	New South Wales	Australia	2050
2	Newcastle Melanoma Unit - Newcastle Mater Misericordiae Hospital	Newcastle	New South Wales	Australia	2298
3	Mater Medical Centre, Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
4	Peter MacCallum Cancer Centre	East Melbourne	Victoria	Australia	3002
5	Austin Health (Ludwig Institute Oncology Unit)	Heidelberg	Victoria	Australia	3084
6	Sir Charles Gairdner Hospital	Nedlands	Western Australia	Australia	6009
7	University of Auckland (Waitemata DHB)	Auckland		New Zealand
8	University Hospital - Birmingham	Birmingham		United Kingdom	B29 6JD
9	Addenbrooke's Hospital	Cambridge		United Kingdom	CB2 2QQ
10	Western Infirmary	Glasgow		United Kingdom	G11 6NT
11	St Georges Hospital	London		United Kingdom	SW17 0RE
12	Royal Marsden Hospital	London		United Kingdom	SW3 6JJ
13	Mount Vernon Hospital	Northwood		United Kingdom	HA6 2RN
14	Weston Park Hospital	Sheffield		United Kingdom	S10 2SJ
15	Southampton University Hospitals	Southampton		United Kingdom	SO16 6YD

Sponsors and Collaborators

• Ludwig Institute for Cancer Research
• Institute of Cancer Research, United Kingdom

Investigators

• Study Chair: Prof. Jonathan S Cebon, MBBS PhD, Ludwig Institute for Cancer Research
• Principal Investigator: Prof. Martin Gore, MBBS PhD, The Royal Marsden Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ludwig Institute for Cancer Research
• ClinicalTrials.gov Identifier: NCT00199901
• Other Study ID Numbers: LUD2003-009
• First Posted: Sep 20, 2005
• Last Update Posted: Apr 8, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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: Phase II; Randomized Controlled Trial; Double-Blind; Cancer Vaccine; NY-ESO-1 protein, human; ISCOMATRIX®, immunological adjuvant
• Additional relevant MeSH terms: Melanoma

Study Results

Participant Flow

Recruitment Details	Patients with resected Stage IIc, lIIb, IIIc and IV melanoma who met eligibility requirements were randomized and stratified by stage of disease to receive 4 intramuscular injections of either NY-ESO-1 ISCOMATRIX® or ISCOMATRIX® adjuvant. The first patient was dosed on 27Sep2005 and the last dose was on 27Jun2007.
Pre-assignment Detail	111 patients were screened and randomized. One patient did not receive study drug. 56 patients were randomized to the NY-ESO-1 ISCOMATRIX® arm and 54 to the ISCOMATRIX® adjuvant arm.

Arm/Group Title	NY-ESO-1 ISCOMATRIX® Vaccine	ISCOMATRIX® Adjuvant
Arm/Group Description	100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
Period Title: Overall Study
STARTED	56	54
COMPLETED	29	30
NOT COMPLETED	27	24

Baseline Characteristics

Arm/Group Title	NY-ESO-1 ISCOMATRIX® Vaccine	ISCOMATRIX® Adjuvant	Total
Arm/Group Description	100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	Total of all reporting groups
Overall Participants	56	54	110
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.5 (13.28)	53.0 (13.90)	53.7 (13.54)
Sex: Female, Male (Count of Participants)
Female	19 33.9%	22 40.7%	41 37.3%
Male	37 66.1%	32 59.3%	69 62.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	2 3.6%	3 5.6%	5 4.5%
Unknown or Not Reported	54 96.4%	51 94.4%	105 95.5%
Race/Ethnicity, Customized (Count of Participants)
White/Caucasian	56 100%	54 100%	110 100%
Region of Enrollment (participants) [Number]
New Zealand	2 3.6%	4 7.4%	6 5.5%
United Kingdom	17 30.4%	15 27.8%	32 29.1%
Australia	37 66.1%	35 64.8%	72 65.5%
ECOG (Count of Participants)
ECOG PS 0	51 91.1%	44 81.5%	95 86.4%
ECOG PS 1	2 3.6%	8 14.8%	10 9.1%
ECOG PS 2	0 0%	0 0%	0 0%
ECOG PS 3	0 0%	0 0%	0 0%
ECOG PS 4	0 0%	0 0%	0 0%
Not Recorded	3 5.4%	2 3.7%	5 4.5%

Outcome Measures

1. Primary Outcome

Title	Rate of Relapse-free Survival at 18 Months
Description	The number of patients who were alive and relapse free 18 months after starting therapy and the number of patients who relapsed or died within 18 months of starting therapy. Disease was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) as measured by CT. Disease progression or relapse was based on an increase of 20% or more in the sum of the longest diameter of target lesions, the appearance of any new lesion as confirmed by CT scan or death.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

All randomized patients who received at least one dose of NY-ESO-1 ISCOMATRIX® vaccine or ISCOMATRIX® adjuvant.

Arm/Group Title	NY-ESO-1 ISCOMATRIX® Vaccine	ISCOMATRIX® Adjuvant
Arm/Group Description	100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
Measure Participants	56	54
Number of patients relapse free at 18 months	29 51.8%	28 51.9%
Number of patients relapsed at 18 months	27 48.2%	26 48.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NY-ESO-1 ISCOMATRIX® Vaccine, ISCOMATRIX® Adjuvant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.913
	Confidence Interval	(2-Sided) 95%; 0.532 to 1.568
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Patients With Treatment -Emergent Adverse Events (TEAEs)
Description	Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, performance status evaluations, electrocardiograms, magnetic resonance imaging, and any other medically indicated assessments, including subject interviews, from the time informed consent is signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

All randomized patients who received at least one dose of NY-ESO-1 ISCOMATRIX® vaccine or ISCOMATRIX® adjuvant.

Arm/Group Title	NY-ESO-1 ISCOMATRIX® Vaccine	ISCOMATRIX® Adjuvant
Arm/Group Description	100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
Measure Participants	56	54
Number of subjects with at least one TEAE	54 96.4%	52 96.3%
Number of subjects with SAE	10 17.9%	12 22.2%
Number of subjects discontinued due to TEAE	2 3.6%	7 13%

3. Secondary Outcome

Title	Relapse-Free Survival During the Entire Period of Observation (up to 6 Years).
Description	Disease was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) as measured by CT. Disease progression or relapse was based on an increase of 20% or more in the sum of the longest diameter of target lesions, the appearance of any new lesion as confirmed by CT scan or death.
Time Frame	through study completion; up to 6 years

Outcome Measure Data

Analysis Population Description

All patients who received at least one dose of NY-ESO-1 ISCOMATRIX® vaccine or ISCOMATRIX® adjuvant.

Arm/Group Title	NY-ESO-1 ISCOMATRIX® Vaccine	ISCOMATRIX® Adjuvant
Arm/Group Description	100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
Measure Participants	56	54
Number of Patients who did not relapse	23 41.1%	25 46.3%
Number of patients who relapsed	33 58.9%	29 53.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NY-ESO-1 ISCOMATRIX® Vaccine, ISCOMATRIX® Adjuvant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.880
	Confidence Interval	(2-Sided) 95%; 0.532 to 1.455
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Overall Survival
Description	Overall Survival measured during the entire Period of Observation (up to 6years). Overall survival was measured from start of treatment to the last follow-up or death.
Time Frame	through study completion; up to 6 years

Outcome Measure Data

Analysis Population Description

All randomized patients who received at least one dose of NY-ESO-1 ISCOMATRIX® vaccine or ISCOMATRIX® adjuvant.

Arm/Group Title	NY-ESO-1 ISCOMATRIX® Vaccine	ISCOMATRIX® Adjuvant
Arm/Group Description	100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
Measure Participants	56	54
Number of Patients Alive at last follow-up	32 57.1%	31 57.4%
Number of Patients Dead at last follow-up	24 42.9%	23 42.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NY-ESO-1 ISCOMATRIX® Vaccine, ISCOMATRIX® Adjuvant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.911
	Confidence Interval	(2-Sided) 95%; 0.514 to 1.614
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	NY-ESO-1 Antibody Response at Baseline Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response
Description	NY-ESO-1-specific antibodies were measured by an enzyme-linked immunosorbent assay ( ELISA) method at baseline and on days 71, 197, 365 and end of study. The results are reported as antibodies to NY-ESO-1-specific Total IgG (reciprocal titer) and were scored on a scale of 0-4 with 0 being no or minimal antibody response (reciprocal titer of 0-100) and 4 a strong antibody response (reciprocal titer of >100,000). The number of patients with each antibody response level are tabulated at each timepoint.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

All randomized patients who received at least one dose of NY-ESO-1 ISCOMATRIX® vaccine or ISCOMATRIX® adjuvant and provided blood samples for analysis at the required time. Patients who discontinued the study prior to the scheduled day were not included at the later timepoints.

Arm/Group Title	NY-ESO-1 ISCOMATRIX® Vaccine	ISCOMATRIX® Adjuvant
Arm/Group Description	100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
Measure Participants	46	45
0	31 55.4%	32 59.3%
1	2 3.6%	0 0%
2	8 14.3%	10 18.5%
3	3 5.4%	2 3.7%
4	2 3.6%	1 1.9%

6. Secondary Outcome

Title	NY-ESO-1 Antibody Response on Day 71 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response
Description	NY-ESO-1-specific antibodies were measured by an enzyme-linked immunosorbent assay ( ELISA) method at baseline and on days 71, 197, 365 and end of study. The results are reported as antibodies to NY-ESO-1-specific Total IgG (reciprocal titer) and were scored on a scale of 0-4 with 0 being no or minimal antibody response (reciprocal titer of 0-100) and 4 a strong antibody response (reciprocal titer of >100,000). The number of patients with each antibody response level are tabulated at each timepoint.
Time Frame	Day 71

Outcome Measure Data

Analysis Population Description

All randomized patients who received at least one dose of NY-ESO-1 ISCOMATRIX® vaccine or ISCOMATRIX® adjuvant and provided blood samples for analysis at the required time. Patients who discontinued the study prior to the scheduled day were not included at the later timepoints.

Arm/Group Title	NY-ESO-1 ISCOMATRIX® Vaccine	ISCOMATRIX® Adjuvant
Arm/Group Description	100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
Measure Participants	43	45
0	0 0%	32 59.3%
1	0 0%	2 3.7%
2	2 3.6%	8 14.8%
3	32 57.1%	2 3.7%
4	9 16.1%	1 1.9%

7. Secondary Outcome

Title	NY-ESO-1 Antibody Response on Day 197 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response
Description	NY-ESO-1-specific antibodies were measured by an enzyme-linked immunosorbent assay ( ELISA) method at baseline and on days 71, 197, 365 and end of study. The results are reported as antibodies to NY-ESO-1-specific Total IgG (reciprocal titer) and were scored on a scale of 0-4 with 0 being no or minimal antibody response (reciprocal titer of 0-100) and 4 a strong antibody response (reciprocal titer of >100,000). The number of patients with each antibody response level are tabulated at each timepoint.
Time Frame	Day 197

Outcome Measure Data

Analysis Population Description

All randomized patients who received at least one dose of NY-ESO-1 ISCOMATRIX® vaccine or ISCOMATRIX® adjuvant and provided blood samples for analysis at the required time. Patients who discontinued the study prior to the scheduled day were not included at the later timepoints.

Arm/Group Title	NY-ESO-1 ISCOMATRIX® Vaccine	ISCOMATRIX® Adjuvant
Arm/Group Description	100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
Measure Participants	34	32
0	0 0%	20 37%
1	0 0%	0 0%
2	3 5.4%	7 13%
3	21 37.5%	5 9.3%
4	10 17.9%	0 0%

8. Secondary Outcome

Title	NY-ESO-1 Antibody Response on Day 365 Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response
Description	NY-ESO-1-specific antibodies were measured by an enzyme-linked immunosorbent assay ( ELISA) method at baseline and on days 71, 197, 365 and end of study. The results are reported as antibodies to NY-ESO-1-specific Total IgG (reciprocal titer) and were scored on a scale of 0-4 with 0 being no or minimal antibody response (reciprocal titer of 0-100) and 4 a strong antibody response (reciprocal titer of >100,000). The number of patients with each antibody response level are tabulated at each timepoint.
Time Frame	Day 365

Outcome Measure Data

Analysis Population Description

All randomized patients who received at least one dose of NY-ESO-1 ISCOMATRIX® vaccine or ISCOMATRIX® adjuvant and provided blood samples for analysis at the required time. Patients who discontinued the study prior to the scheduled day were not included at the later timepoints.

Arm/Group Title	NY-ESO-1 ISCOMATRIX® Vaccine	ISCOMATRIX® Adjuvant
Arm/Group Description	100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
Measure Participants	27	29
0	0 0%	19 35.2%
1	1 1.8%	0 0%
2	3 5.4%	6 11.1%
3	22 39.3%	4 7.4%
4	1 1.8%	0 0%

9. Secondary Outcome

Title	NY-ESO-1 Antibody Response at End of Study Reported on a Scale of 0 to 4 With 0 Being no or Minimal Antibody Response and 4 the Highest Antibody Response
Description	NY-ESO-1-specific antibodies were measured by an enzyme-linked immunosorbent assay ( ELISA) method at baseline and on days 71, 197, 365 and end of study. The results are reported as antibodies to NY-ESO-1-specific Total IgG (reciprocal titer) and were scored on a scale of 0-4 with 0 being no or minimal antibody response (reciprocal titer of 0-100) and 4 a strong antibody response (reciprocal titer of >100,000). The number of patients with each antibody response level are tabulated at each timepoint.
Time Frame	End of Study (month 18)

Outcome Measure Data

Analysis Population Description

All randomized patients who received at least one dose of NY-ESO-1 ISCOMATRIX® vaccine or ISCOMATRIX® adjuvant and provided blood samples for analysis at the required time. Patients who discontinued the study prior to the scheduled day were not included at the later timepoints.

Arm/Group Title	NY-ESO-1 ISCOMATRIX® Vaccine	ISCOMATRIX® Adjuvant
Arm/Group Description	100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).	120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
Measure Participants	37	36
0	0 0%	26 48.1%
1	2 3.6%	2 3.7%
2	6 10.7%	4 7.4%
3	26 46.4%	4 7.4%
4	3 5.4%	0 0%

Adverse Events

Time Frame	Adverse events (AEs) were documented from informed consent through 18 months (regardless of causality to study drug).
Adverse Event Reporting Description	Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Adverse events (AEs) were documented from the time informed consent was signed through 18 months. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Arm/Group Title	NY-ESO-1 ISCOMATRIX® Vaccine		ISCOMATRIX® Adjuvant
Arm/Group Description	100 μg of NY-ESO-1 protein formulated with 120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of NY-ESO-1 ISCOMATRIX® vaccine. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).		120 μg of ISCOMATRIX® adjuvant. Each patient received four intramuscular injections of ISCOMATRIX® adjuvant. The first three doses were given at four-week intervals, days 1, 29, and 57, (± 3 days of scheduled date). The fourth injection was given at month 6 (day 183 ± 3 days).
All Cause Mortality
	NY-ESO-1 ISCOMATRIX® Vaccine		ISCOMATRIX® Adjuvant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/56 (42.9%)		23/54 (42.6%)
Serious Adverse Events
	NY-ESO-1 ISCOMATRIX® Vaccine		ISCOMATRIX® Adjuvant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/56 (17.9%)		12/54 (22.2%)
Blood and lymphatic system disorders
Anemia	1/56 (1.8%)		0/54 (0%)
Lymphadenopathy	0/56 (0%)		1/54 (1.9%)
Gastrointestinal disorders
Abdominal neoplasm	0/56 (0%)		1/54 (1.9%)
General disorders
Chest pain	1/56 (1.8%)		0/54 (0%)
Injury, poisoning and procedural complications
Road Traffic Accident	0/56 (0%)		1/54 (1.9%)
Seroma	1/56 (1.8%)		0/54 (0%)
Musculoskeletal and connective tissue disorders
Radius fracture	0/56 (0%)		1/54 (1.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases	2/56 (3.6%)		3/54 (5.6%)
Skin and subcutaneous tissue disorders
Cellulitis	1/56 (1.8%)		1/54 (1.9%)
Malignant melanoma	2/56 (3.6%)		0/54 (0%)
Subcutaneous nodule	0/56 (0%)		1/54 (1.9%)
Surgical and medical procedures
Mass excision	3/56 (5.4%)		2/54 (3.7%)
Radioactive iodine therapy	1/56 (1.8%)		0/54 (0%)
Thyroidectomy	1/56 (1.8%)		0/54 (0%)
Vascular disorders
Cerebral artery stenosis	0/56 (0%)		1/54 (1.9%)
Transient ischemic attack	0/56 (0%)		1/54 (1.9%)
Other (Not Including Serious) Adverse Events
	NY-ESO-1 ISCOMATRIX® Vaccine		ISCOMATRIX® Adjuvant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/56 (96.4%)		52/54 (96.3%)
Blood and lymphatic system disorders
lymphadenopathy	4/56 (7.1%)		1/54 (1.9%)
Gastrointestinal disorders
nausea	9/56 (16.1%)		7/54 (13%)
abdominal pain	1/56 (1.8%)		5/54 (9.3%)
diarrhea	1/56 (1.8%)		3/54 (5.6%)
General disorders
chills	6/56 (10.7%)		1/54 (1.9%)
fatigue	13/56 (23.2%)		16/54 (29.6%)
influenza like illness	26/56 (46.4%)		9/54 (16.7%)
injection site discomfort	5/56 (8.9%)		1/54 (1.9%)
injection site erythema	9/56 (16.1%)		1/54 (1.9%)
injection site pain	28/56 (50%)		17/54 (31.5%)
injection site reaction	16/56 (28.6%)		11/54 (20.4%)
lethargy	5/56 (8.9%)		3/54 (5.6%)
malaise	3/56 (5.4%)		0/54 (0%)
pyrexia	6/56 (10.7%)		2/54 (3.7%)
mass	1/56 (1.8%)		3/54 (5.6%)
Musculoskeletal and connective tissue disorders
arthralgia	8/56 (14.3%)		6/54 (11.1%)
back pain	6/56 (10.7%)		5/54 (9.3%)
musculoskeletal pain	3/56 (5.4%)		3/54 (5.6%)
pain in extremity	9/56 (16.1%)		6/54 (11.1%)
Nervous system disorders
headache	18/56 (32.1%)		13/54 (24.1%)
dizziness	2/56 (3.6%)		3/54 (5.6%)
paresthesia	1/56 (1.8%)		3/54 (5.6%)
Respiratory, thoracic and mediastinal disorders
cough	11/56 (19.6%)		3/54 (5.6%)
nasopharyngitis	4/56 (7.1%)		2/54 (3.7%)
pharyngolaryngeal pain	3/56 (5.4%)		4/54 (7.4%)
influenza	1/56 (1.8%)		3/54 (5.6%)
Skin and subcutaneous tissue disorders
rash	4/56 (7.1%)		5/54 (9.3%)
basal cell carcinoma	0/56 (0%)		3/54 (5.6%)
Surgical and medical procedures
mass excision	3/56 (5.4%)		1/54 (1.9%)
skin lesion excision	2/56 (3.6%)		4/54 (7.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.