Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Vaccines

Cyclophosphamide

Adjuvants, Immunologic

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

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.

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.

NY-ESO-1 ISCOMATRIX® vaccine

Jonathan S Cebon, FRACP, MBBS, PhD

Ian D Davis, FRACP, FAChPM, MBBS, PhD

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.

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.

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.

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

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

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.

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.

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.

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.

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.

Austin Health

Peter MacCallum Cancer Institute

Ludwig Institute for Cancer Research

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.

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.

Cohort 1: NY-ESO-1 ISCOM

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.

Cohort 2: Cyclophosphamide + NY-ESO-1 ISCOM

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Australia

Region of Enrollment

Karnofsky scores represent the following performance status categories:

70: Cares for self; unable to carry on normal activity or to do active work. 80: Normal activity with effort; some signs or symptoms of disease. 90: Able to carry on normal activity; minor signs or symptoms of disease. 100: Normal no complaints; no evidence of disease.

Karnofsky Performance Status

Jonathan Skipper PhD

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

Number of Subjects With Best Overall Tumor Response

CD4+ T-cell Response at BL and Post-BL

New CD4+ T-cell Response Post-BL

CD8+ T-cell Response at BL and Post-BL

New CD8+ T-cell Response Post-BL

No CD4+ or CD8+ T-cell Response

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

Cellular Immunogenicity of the NY-ESO-1 ISCOM Vaccine

Reaction at Pretreatment and Week 11

Reaction at Pretreatment and Week 23

Reaction at Pretreatment, No Reaction On Study

Reaction at Pretreatment, No On Study DTH Results

No Reaction Pretreatment , Reaction at Week 11

No Reaction Pretreatment , Reaction at Week 23

No Reaction Pretreatment or on Study

No Reaction Pretreatment, No On Study DTH Results

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

Post-Vaccination Delayed-type Hypersensitivity (DTH) Reactions

NY-ESO-1 (+) at BL and Post-BL

NY-ESO-1 (-) at BL, converted to (+) Post-BL

NY-ESO-1 (-) at BL and Post-BL

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

Humoral Immunogenicity of the NY-ESO-1 ISCOM Vaccine

Any TEAE

Maximum Grade 3 TEAE

Maximum Grade 4 TEAE

Treatment-related TEAE

Serious TEAE

Death

TEAE Leading to Discontinuation

Dose-limiting Toxicity

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

Number of Subjects With Treatment-emergent Adverse Events

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of NY-ESO-1 ISCOMATRIX® in Patients With Measurable Stage III or IV Melanoma	NCT00518206	Melanoma	NY-ESO-1 ISCOMA... Cyclophosphamid...	18 Years -	Ludwig Institute for Cancer Research
Study of NY-ESO-1 ISCOMATRIX® in Patients With Measurable Stage III or IV Melanoma	NCT00518206	Melanoma	NY-ESO-1 ISCOMA... Cyclophosphamid...	18 Years -	Ludwig Institute for Cancer Research

Spots Global Cancer Trial Database for iscomatrix, immunological adjuvant