NY-ESO-1 Vaccine in Combination With Ipilimumab in Patients With Unresectable or Metastatic Melanoma

• Sponsor: Ludwig Institute for Cancer Research (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01810016
• Collaborator: Cancer Research Institute, NY, USA (Other)
• Enrollment: 8
• Locations: 5
• Arms: 3
• Actual Duration (Months): 27.7
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This was a Phase 1, open-label, non-randomized study of the combination of NY-ESO-1 plus ipilimumab in patients with unresectable or metastatic melanoma for whom treatment with ipilimumab was indicated. Patients must have had evidence of NY-ESO-1 or LAGE-1 tumor positivity and radiologically measurable disease by the immune-related Response Criteria (irRC). Primary study objectives were to determine the safety and tolerability of the combination and to evaluate humoral and cellular immune response. Secondary objectives were to evaluate tumor response and immunological changes in the tumor microenvironment.

Condition or Disease	Intervention/Treatment	Phase
Unresectable or Metastatic Melanoma	Biological: Ipilimumab; Biological: NY-ESO-1 Protein Vaccine; Biological: NY-ESO-1 OLP4 Vaccine with Poly-ICLC and Montanide; Biological: NY-ESO-1 OLP4 Vaccine with Poly-ICLC	Phase 1

Detailed Description

Patients were enrolled sequentially, alternating among 3 treatment arms. Study treatment comprised ipilimumab 3 mg/kg administered intravenously (IV) over 90 minutes every 3 weeks for 4 doses followed by the NY-ESO-1 vaccine administered subcutaneously (SC). Arm A received the NY-ESO-1 recombinant protein mixed with polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (Poly-ICLC) and Montanide; Arm B received NY-ESO-1 overlapping long peptides 4 (OLP4) mixed with Poly-ICLC and Montanide; and Arm C received NY-ESO-1 OLP4 mixed with Poly-ICLC (without Montanide). The vaccine was administered immediately following the ipilimumab infusion, and patients were observed for 1 hour following administration. No dose adjustments or delays were permitted.

Because the study treatment regimens had not been previously investigated in humans, the first patient in each treatment arm was followed for 28 days and evaluated for any regimen-limiting toxicity (RLT), defined as any dose-limiting toxicity (DLT) that could not be attributed solely to either the vaccine or ipilimumab and was therefore considered to be related to the combination. If an RLT was observed in the first patient, the second patient was to be evaluated for 28 days before the third patient was enrolled. If at any point ≥ 2 RLTs were observed in a treatment arm, accrual to that arm was to be terminated and the combination in that arm was to be declared unsafe.

Patients were monitored for safety, immune and tumor response, and immunological changes in the tumor microenvironment for the duration of study participation, which may have been up to 6 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Study of NY-ESO-1 Vaccine in Combination With Ipilimumab in Patients With Unresectable or Metastatic Melanoma, for Whom Treatment With Ipilimumab is Indicated
• Actual Study Start Date: Jan 24, 2014
• Actual Primary Completion Date: May 17, 2016
• Actual Study Completion Date: May 17, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A Ipilimumab (IV) followed by NY-ESO-1 recombinant protein mixed with Poly-ICLC and Montanide (SC) every 3 weeks for 4 doses.	Biological: Ipilimumab; Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses.; Other Names: Yervoy ; Biological: NY-ESO-1 Protein Vaccine; NY-ESO-1 recombinant protein (250 µg) was mixed with Poly-ICLC (1 mg) and Montanide ISA-51 VG (1 mL) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.
Experimental: Arm B Ipilimumab (IV) followed by NY-ESO-1 OLP4 mixed with Poly-ICLC and Montanide (SC) every 3 weeks for 4 doses.	Biological: Ipilimumab; Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses.; Other Names: Yervoy ; Biological: NY-ESO-1 OLP4 Vaccine with Poly-ICLC and Montanide; NY-ESO-1 OLP4 (1 mg) was mixed in 5% dextrose solution in water with Poly-ICLC (1 mg) and Montanide ISA-51 VG (1 mL) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.
Experimental: Arm C Ipilimumab (IV) followed by NY-ESO-1 OLP4 mixed with Poly-ICLC (SC) every 3 weeks for 4 doses.	Biological: Ipilimumab; Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses.; Other Names: Yervoy ; Biological: NY-ESO-1 OLP4 Vaccine with Poly-ICLC; NY-ESO-1 OLP4 (1 mg) was mixed in 5% dextrose solution in water with Poly-ICLC (1 mg) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Treatment-emergent Adverse Events [Continuously for up to 6 months]

   Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. 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 (DLT) was defined as any ≥ Grade 3 hematologic or non-hematologic toxicity that was definitely, probably, or possibly related to the administration of the NY-ESO-1 vaccine or as any toxicity that was definitely, probably, or possibly related to ipilimumab and required permanent discontinuation of ipilimumab in accordance with local prescribing information. DLT assessments were based on the combination of all vaccine components, not on the components individually.

Secondary Outcome Measures

1. Number of Patients With Immune-related Tumor Response at the Last Assessment [Up to 5 months]

   Immune-related tumor response was evaluated using the imaging techniques considered appropriate by the Investigators at Baseline, Week 13, and at the end of the study (Week 20 ± 1 week). Tumor response was designated according to the immune-related Response Criteria (irRC) (Wolchok et al. Clin Cancer Res 2009;15:7412-20) into the following categories: immune-related complete response (irCR) requires disappearance of all lesions in two consecutive observations not less than 4 weeks apart; immune-related partial response (irPR) requires ≥ 50% decrease in tumor burden compared with baseline in two observations at least 4 weeks apart; immune-related stable disease (irSD) is assigned when neither a 50% decrease from baseline tumor burden nor a 25% increase in tumor burden from nadir can be established; immune-related progressive disease (irPD) requires a ≥ 25% increase from nadir in tumor burden at any single time point in two consecutive observations at least 4 weeks apart.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Patients with unresectable or metastatic melanoma, for whom treatment with ipilimumab was indicated as per ipilimumab/Yervoy® package insert (applicable for United States [US] sites) or product information (applicable for Australia site).

2. Radiologically measurable disease by irRC.

3. Tumor expression of NY-ESO-1 or LAGE-1 antigen by immunohistochemistry or reverse transcriptase-polymerase chain reaction (RT-PCR), or evidence of seropositivity to NY-ESO-1 or LAGE-1.

4. Willingness to provide at least one pre-and post-vaccination tumor biopsy sample.

5. Expected survival of at least 4 months.

6. At the time of Day 1 of the study, patients must have been at least 3 weeks since surgery.

7. At the time of Day 1 of the study, patients with brain metastases must have been asymptomatic and:

• at least 8 weeks without tumor progression after any whole brain radiotherapy;

• at least 4 weeks since craniotomy and resection or stereotactic radiosurgery;

• at least 3 weeks without new brain metastases as evidenced by magnetic resonance imaging (MRI).

1. Eastern Cooperative Oncology Group performance status of 0 to 2.

2. Laboratory parameters for vital functions must have been in the normal range. Laboratory abnormalities that were not clinically significant were generally permitted, except for the following laboratory parameters, which must have been within the ranges specified:

• hemoglobin: ≥ 10 g/dL;

• neutrophil count: ≥ 1.5 x 10^9/L;

• lymphocyte count: ≥ lower limit of normal (LLN);

• platelet count: ≥ 80 x 10^9/L;

• serum creatinine: ≤ 2 mg/dL;

• serum bilirubin: ≤ 2 x upper limit of normal (ULN);

• aspartate aminotransferase (AST)/alanine aminotransferase (ALT): ≤ 2 x ULN.

1. Had been informed of other treatment options.

2. Age ≥ 18 years.

3. Able and willing to give valid written informed consent.

Exclusion Criteria:

1. Any contraindications for ipilimumab/Yervoy® as per package insert (applicable for US sites) or product information (applicable for Australia site).

2. Prior exposure to NY-ESO-1 vaccine.

3. Active autoimmune disease, symptoms or conditions except for vitiligo, type I diabetes, treated thyroiditis, asymptomatic laboratory evidence of autoimmune disease (e.g., +antinuclear antibody [ANA], +rheumatoid factor [RF], antithyroglobulin antibodies), or mild arthritis requiring no therapy or manageable with nonsteroidal anti-inflammatory drugs (NSAIDs).

4. Unresolved immune-related adverse events following prior biological therapy.

5. Systemic treatment with high-dose corticosteroids (greater than prednisone 10 mg daily or equivalent).

6. Treatment with protocol-specified non-permitted concomitant therapies.

7. Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may have been available.

8. Myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, chest pain or shortness of breath with activity, or other heart conditions being treated by a doctor.

9. Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.

10. Known immunodeficiency or human immunodeficiency virus positivity, active Hepatitis B or active Hepatitis C.

11. History of severe allergic reactions to vaccines or unknown allergens.

12. Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders).

13. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to Day 1 of the study.

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

15. Lack of availability for immunological and clinical follow-up assessments.

16. Women who were breast feeding or pregnant as evidenced by positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) done within 14 days prior to first dosing and urine test within 72 hours prior to first dosing.

17. Women of childbearing potential not using a medically acceptable means of contraception for the duration of the study.

18. Any condition that, in the clinical judgment of the treating physician, was likely to prevent the patient from complying with any aspect of the protocol or that may have put the patient at unacceptable risk.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mount Sinai Medical Center	New York	New York	United States	10029
2	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
3	University of Pittsburgh Cancer Center	Pittsburgh	Pennsylvania	United States	15213
4	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908
5	Austin Health, Ludwig Oncology Unit	Melbourne	Victoria	Australia

Sponsors and Collaborators

• Ludwig Institute for Cancer Research
• Cancer Research Institute, NY, USA

Investigators

• Study Chair: Michael A Postow, MD, Memorial Sloan Kettering Cancer Center
• Principal Investigator: Hassane M Zarour, MD, University of Pittsburgh
• Principal Investigator: Craig L Slingluff, MD, University of Virginia
• Principal Investigator: Jonathan Cebon, MBBS, FRACP, PhD, Austin Health, Ludwig Oncology Unit
• Principal Investigator: Philip Friedlander, MD, Icahn School of Medicine at Mount Sinai

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ludwig Institute for Cancer Research
• ClinicalTrials.gov Identifier: NCT01810016
• Other Study ID Numbers: LUD2012-004
• First Posted: Mar 13, 2013
• Last Update Posted: Nov 30, 2018
• Last Verified: Nov 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Ludwig Institute for Cancer Research: NY-ESO-1; Metastatic Melanoma; Ipilimumab; Phase I; Adjuvant; Immunologic; Vaccination; Immunotherapy; Neoplasm
• Additional relevant MeSH terms: Melanoma; Poly I-C; Ipilimumab; Carboxymethylcellulose Sodium; Vaccines; Monatide (IMS 3015); Poly ICLC

Study Results

Participant Flow

Arm/Group Title	Arm A (Ipi, NY-ESO-1 Protein)	Arm B (Ipi, NY-ESO-1 OLP4)	Arm C (Ipi, NY-ESO-1 OLP4)
Arm/Group Description	Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses. NY-ESO-1 recombinant protein (250 µg) was mixed with Poly-ICLC (1 mg) and Montanide ISA-51 VG (1 mL) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.	Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses. NY-ESO-1 OLP4 (1 mg) was mixed in 5% dextrose solution in water with Poly-ICLC (1 mg) and Montanide ISA-51 VG (1 mL) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.	Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses. NY-ESO-1 OLP4 (1 mg) was mixed in 5% dextrose solution in water with Poly-ICLC (1 mg) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.
Period Title: Overall Study
STARTED	5	2	1
COMPLETED	4	1	0
NOT COMPLETED	1	1	1

Baseline Characteristics

Arm/Group Title	Arm A (Ipi, NY-ESO-1 Protein)	Arm B (Ipi, NY-ESO-1 OLP4)	Arm C (Ipi, NY-ESO-1 OLP4)	Total
Arm/Group Description	Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses. NY-ESO-1 recombinant protein (250 µg) was mixed with Poly-ICLC (1 mg) and Montanide ISA-51 VG (1 mL) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.	Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses. NY-ESO-1 OLP4 (1 mg) was mixed in 5% dextrose solution in water with Poly-ICLC (1 mg) and Montanide ISA-51 VG (1 mL) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.	Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses. NY-ESO-1 OLP4 (1 mg) was mixed in 5% dextrose solution in water with Poly-ICLC (1 mg) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.	Total of all reporting groups
Overall Participants	5	2	1	8
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.0 (7.7)	61.5 (7.8)	71.0 (NA)	63.6 (7.2)
Sex: Female, Male (Count of Participants)
Female	1 20%	0 0%	1 100%	2 25%
Male	4 80%	2 100%	0 0%	6 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	5 100%	2 100%	0 0%	7 87.5%
Unknown or Not Reported	0 0%	0 0%	1 100%	1 12.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	5 100%	2 100%	0 0%	7 87.5%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	1 100%	1 12.5%
Region of Enrollment (participants) [Number]
United States	5 100%	2 100%	1 100%	8 100%
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	36.6 (11.5)	26.2 (0.2)	29.0 (NA)	32.5 (9.6)
Eastern Cooperative Oncology Group Performance Status (Count of Participants)
0	3 60%	1 50%	0 0%	4 50%
1	2 40%	1 50%	1 100%	4 50%
Tumor Stage at Study Entry (Count of Participants)
IIIC	1 20%	0 0%	0 0%	1 12.5%
IV	4 80%	2 100%	1 100%	7 87.5%
Antigen (Count of Participants)
NY-ESO-1	1 20%	2 100%	0 0%	3 37.5%
LAGE-1	0 0%	0 0%	0 0%	0 0%
None	4 80%	0 0%	1 100%	5 62.5%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Treatment-emergent Adverse Events
Description	Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. 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 (DLT) was defined as any ≥ Grade 3 hematologic or non-hematologic toxicity that was definitely, probably, or possibly related to the administration of the NY-ESO-1 vaccine or as any toxicity that was definitely, probably, or possibly related to ipilimumab and required permanent discontinuation of ipilimumab in accordance with local prescribing information. DLT assessments were based on the combination of all vaccine components, not on the components individually.
Time Frame	Continuously for up to 6 months

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set includes all patients who received at least 1 dose of study treatment.

Arm/Group Title	Arm A (Ipi, NY-ESO-1 Protein)	Arm B (Ipi, NY-ESO-1 OLP4)	Arm C (Ipi, NY-ESO-1 OLP4)
Arm/Group Description	Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses. NY-ESO-1 recombinant protein (250 µg) was mixed with Poly-ICLC (1 mg) and Montanide ISA-51 VG (1 mL) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.	Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses. NY-ESO-1 OLP4 (1 mg) was mixed in 5% dextrose solution in water with Poly-ICLC (1 mg) and Montanide ISA-51 VG (1 mL) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.	Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses. NY-ESO-1 OLP4 (1 mg) was mixed in 5% dextrose solution in water with Poly-ICLC (1 mg) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.
Measure Participants	5	2	1
Any TEAE	5 100%	2 100%	1 100%
Maximum grade 1 TEAE	1 20%	1 50%	0 0%
Maximum grade 2 TEAE	2 40%	1 50%	0 0%
Maximum grade 3 TEAE	2 40%	0 0%	0 0%
Maximum grade 4 TEAE	0 0%	0 0%	0 0%
Maximum grade 5 TEAE	0 0%	0 0%	1 100%
NY-ESO-1-related TEAE	4 80%	2 100%	0 0%
Ipilimumab-related TEAE	5 100%	2 100%	0 0%
Serious TEAE	2 40%	0 0%	1 100%
TEAE Leading to Treatment Discontinuation	0 0%	0 0%	1 100%
TEAE Meeting DLT Criteria	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Number of Patients With Immune-related Tumor Response at the Last Assessment
Description	Immune-related tumor response was evaluated using the imaging techniques considered appropriate by the Investigators at Baseline, Week 13, and at the end of the study (Week 20 ± 1 week). Tumor response was designated according to the immune-related Response Criteria (irRC) (Wolchok et al. Clin Cancer Res 2009;15:7412-20) into the following categories: immune-related complete response (irCR) requires disappearance of all lesions in two consecutive observations not less than 4 weeks apart; immune-related partial response (irPR) requires ≥ 50% decrease in tumor burden compared with baseline in two observations at least 4 weeks apart; immune-related stable disease (irSD) is assigned when neither a 50% decrease from baseline tumor burden nor a 25% increase in tumor burden from nadir can be established; immune-related progressive disease (irPD) requires a ≥ 25% increase from nadir in tumor burden at any single time point in two consecutive observations at least 4 weeks apart.
Time Frame	Up to 5 months

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set includes all patients who received at least 1 dose of study treatment.

Arm/Group Title	Arm A (Ipi, NY-ESO-1 Protein)	Arm B (Ipi, NY-ESO-1 OLP4)	Arm C (Ipi, NY-ESO-1 OLP4)
Arm/Group Description	Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses. NY-ESO-1 recombinant protein (250 µg) was mixed with Poly-ICLC (1 mg) and Montanide ISA-51 VG (1 mL) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.	Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses. NY-ESO-1 OLP4 (1 mg) was mixed in 5% dextrose solution in water with Poly-ICLC (1 mg) and Montanide ISA-51 VG (1 mL) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.	Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses. NY-ESO-1 OLP4 (1 mg) was mixed in 5% dextrose solution in water with Poly-ICLC (1 mg) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.
Measure Participants	5	2	1
irSD at Last Assessment	4 80%	0 0%	0 0%
irPD at Last Assessment	0 0%	2 100%	0 0%
Not evaluated	1 20%	0 0%	1 100%

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 6 months.
Adverse Event Reporting Description	AE documentation included onset/resolution dates, severity using the NCI CTCAE (version 4.0), seriousness, relationship to study drug, 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 patient at the maximum reported grade.
Arm/Group Title	Arm A (Ipi, NY-ESO-1 Protein)		Arm B (Ipi, NY-ESO-1 OLP4)		Arm C (Ipi, NY-ESO-1 OLP4)
Arm/Group Description	Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses. NY-ESO-1 recombinant protein (250 µg) was mixed with Poly-ICLC (1 mg) and Montanide ISA-51 VG (1 mL) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.		Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses. NY-ESO-1 OLP4 (1 mg) was mixed in 5% dextrose solution in water with Poly-ICLC (1 mg) and Montanide ISA-51 VG (1 mL) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.		Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses. NY-ESO-1 OLP4 (1 mg) was mixed in 5% dextrose solution in water with Poly-ICLC (1 mg) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.
All Cause Mortality
	Arm A (Ipi, NY-ESO-1 Protein)		Arm B (Ipi, NY-ESO-1 OLP4)		Arm C (Ipi, NY-ESO-1 OLP4)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/2 (0%)		1/1 (100%)
Serious Adverse Events
	Arm A (Ipi, NY-ESO-1 Protein)		Arm B (Ipi, NY-ESO-1 OLP4)		Arm C (Ipi, NY-ESO-1 OLP4)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40%)		0/2 (0%)		1/1 (100%)
Endocrine disorders
Hypophysitis	1/5 (20%)		0/2 (0%)		0/1 (0%)
Adrenal insufficiency	1/5 (20%)		0/2 (0%)		0/1 (0%)
Gastrointestinal disorders
Colitis	1/5 (20%)		0/2 (0%)		0/1 (0%)
Diarrhoea	1/5 (20%)		0/2 (0%)		0/1 (0%)
General disorders
Asthenia	0/5 (0%)		0/2 (0%)		1/1 (100%)
Infections and infestations
Cellulitis	0/5 (0%)		0/2 (0%)		1/1 (100%)
Metabolism and nutrition disorders
Lactic acidosis	0/5 (0%)		0/2 (0%)		1/1 (100%)
Dehydration	1/5 (20%)		0/2 (0%)		0/1 (0%)
Hypokalaemia	1/5 (20%)		0/2 (0%)		0/1 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm	0/5 (0%)		0/2 (0%)		1/1 (100%)
Psychiatric disorders
Confusional state	0/5 (0%)		0/2 (0%)		1/1 (100%)
Renal and urinary disorders
Renal failure acute	1/5 (20%)		0/2 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Arm A (Ipi, NY-ESO-1 Protein)		Arm B (Ipi, NY-ESO-1 OLP4)		Arm C (Ipi, NY-ESO-1 OLP4)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		2/2 (100%)		1/1 (100%)
Blood and lymphatic system disorders
Anaemia	0/5 (0%)		0/2 (0%)		1/1 (100%)
Cardiac disorders
Tachycardia	0/5 (0%)		0/2 (0%)		1/1 (100%)
Endocrine disorders
Hyperthyroidism	1/5 (20%)		0/2 (0%)		0/1 (0%)
Eye disorders
Ocular hyperaemia	1/5 (20%)		0/2 (0%)		0/1 (0%)
Scleral discolouration	1/5 (20%)		0/2 (0%)		0/1 (0%)
Gastrointestinal disorders
Diarrhoea	1/5 (20%)		2/2 (100%)		0/1 (0%)
Abdominal pain	2/5 (40%)		0/2 (0%)		0/1 (0%)
Nausea	2/5 (40%)		0/2 (0%)		0/1 (0%)
Abdominal distension	1/5 (20%)		0/2 (0%)		0/1 (0%)
Abnormal faeces	1/5 (20%)		0/2 (0%)		0/1 (0%)
Constipation	0/5 (0%)		0/2 (0%)		1/1 (100%)
Dyspepsia	1/5 (20%)		0/2 (0%)		0/1 (0%)
Gastric dilatation	1/5 (20%)		0/2 (0%)		0/1 (0%)
Large intestinal haemorrhage	1/5 (20%)		0/2 (0%)		0/1 (0%)
Large intestine perforation	1/5 (20%)		0/2 (0%)		0/1 (0%)
Vomiting	1/5 (20%)		0/2 (0%)		0/1 (0%)
General disorders
Fatigue	3/5 (60%)		1/2 (50%)		1/1 (100%)
Injection site reaction	4/5 (80%)		1/2 (50%)		0/1 (0%)
Pyrexia	2/5 (40%)		0/2 (0%)		1/1 (100%)
Chills	1/5 (20%)		0/2 (0%)		1/1 (100%)
Oedema peripheral	1/5 (20%)		0/2 (0%)		1/1 (100%)
Generalised oedema	1/5 (20%)		0/2 (0%)		0/1 (0%)
Localised oedema	0/5 (0%)		0/2 (0%)		1/1 (100%)
Mucosal inflammation	1/5 (20%)		0/2 (0%)		0/1 (0%)
Pain	0/5 (0%)		0/2 (0%)		1/1 (100%)
Xerosis	1/5 (20%)		0/2 (0%)		0/1 (0%)
Infections and infestations
Clostridial infection	0/5 (0%)		1/2 (50%)		0/1 (0%)
Lower respiratory tract infection	0/5 (0%)		1/2 (50%)		0/1 (0%)
Skin infection	0/5 (0%)		0/2 (0%)		1/1 (100%)
Upper respiratory tract infection	0/5 (0%)		1/2 (50%)		0/1 (0%)
Injury, poisoning and procedural complications
Procedural pain	0/5 (0%)		1/2 (50%)		0/1 (0%)
Wound dehiscence	1/5 (20%)		0/2 (0%)		0/1 (0%)
Investigations
Blood creatinine increased	1/5 (20%)		0/2 (0%)		0/1 (0%)
Blood phosphorus decreased	1/5 (20%)		0/2 (0%)		0/1 (0%)
Blood sodium decreased	1/5 (20%)		0/2 (0%)		0/1 (0%)
Lymphocyte count decreased	1/5 (20%)		0/2 (0%)		0/1 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/5 (20%)		0/2 (0%)		1/1 (100%)
Dehydration	1/5 (20%)		0/2 (0%)		0/1 (0%)
Hypokalaemia	0/5 (0%)		0/2 (0%)		1/1 (100%)
Hypercalcaemia	1/5 (20%)		0/2 (0%)		0/1 (0%)
Hyperkalaemia	1/5 (20%)		0/2 (0%)		0/1 (0%)
Hyponatraemia	1/5 (20%)		0/2 (0%)		0/1 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	2/5 (40%)		0/2 (0%)		0/1 (0%)
Arthralgia	1/5 (20%)		0/2 (0%)		0/1 (0%)
Back pain	0/5 (0%)		1/2 (50%)		0/1 (0%)
Neck pain	1/5 (20%)		0/2 (0%)		0/1 (0%)
Pain in extremity	0/5 (0%)		1/2 (50%)		0/1 (0%)
Nervous system disorders
Paraesthesia	1/5 (20%)		0/2 (0%)		0/1 (0%)
Psychiatric disorders
Insomnia	1/5 (20%)		0/2 (0%)		1/1 (100%)
Anxiety	0/5 (0%)		0/2 (0%)		1/1 (100%)
Renal and urinary disorders
Urinary retention	1/5 (20%)		0/2 (0%)		0/1 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/5 (20%)		1/2 (50%)		0/1 (0%)
Pleural effusion	1/5 (20%)		0/2 (0%)		1/1 (100%)
Atelectasis	1/5 (20%)		0/2 (0%)		0/1 (0%)
Dyspnoea	0/5 (0%)		0/2 (0%)		1/1 (100%)
Dyspnoea exertional	1/5 (20%)		0/2 (0%)		0/1 (0%)
Epistaxis	1/5 (20%)		0/2 (0%)		0/1 (0%)
Hypoxia	1/5 (20%)		0/2 (0%)		0/1 (0%)
Oropharyngeal pain	1/5 (20%)		0/2 (0%)		0/1 (0%)
Pneumonia aspiration	1/5 (20%)		0/2 (0%)		0/1 (0%)
Skin and subcutaneous tissue disorders
Pruritus	4/5 (80%)		0/2 (0%)		1/1 (100%)
Rash	3/5 (60%)		0/2 (0%)		0/1 (0%)
Skin induration	1/5 (20%)		2/2 (100%)		0/1 (0%)
Rash generalised	1/5 (20%)		1/2 (50%)		0/1 (0%)
Alopecia	0/5 (0%)		1/2 (50%)		0/1 (0%)
Dermatitis acneiform	1/5 (20%)		0/2 (0%)		0/1 (0%)
Dermatitis contact	0/5 (0%)		1/2 (50%)		0/1 (0%)
Dry skin	1/5 (20%)		0/2 (0%)		0/1 (0%)
Erythema	0/5 (0%)		0/2 (0%)		1/1 (100%)
Hyperhidrosis	0/5 (0%)		0/2 (0%)		1/1 (100%)
Mechanical urticaria	1/5 (20%)		0/2 (0%)		0/1 (0%)
Rash maculo-papular	1/5 (20%)		0/2 (0%)		0/1 (0%)
Vascular disorders
Hypotension	2/5 (40%)		0/2 (0%)		0/1 (0%)
Embolism	1/5 (20%)		0/2 (0%)		0/1 (0%)
Hypertension	1/5 (20%)		0/2 (0%)		0/1 (0%)

Limitations/Caveats

As the study was terminated early due to slow enrollment, immune response (humoral and cellular) analyses were not performed as outlined in the protocol due to small sample sizes within each arm.

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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.