NY-ESO-1 Protein With Montanide and CpG 7909 as Cancer Vaccine in Several Tumors

NCT00299728 | Completed Phase 1 Results FDA Drug

• 1 other identifier: LUD2003-022;NYU05-120;CUMC9147
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase I, open-label, randomized study of NY-ESO-l protein with immune adjuvants CpG 7909 and Montanide ISA-51 VG in patients with tumors that often express NY-ESO-1. The vaccinations was to be administered subcutaneously every 3 weeks for 4 doses. Patients with any malignancy that is known to frequently express NY-ESO-1 were eligible, regardless of whether antigen expression in the autologous tumor could be demonstrated or not by either PCR or immunohistochemistry. The primary objective of the study was to define safety. Secondarily, the study was to evaluate whether patients developed a specific immunologic response to the NY-ESO-1 protein. Blood samples were to be obtained at baseline, prior to each vaccination, one week after each vaccination, and at the last study visit for the assessment of NY-ESO-1-specific CD4+ and CD8+ T cells. Cytokine secretion by NY-ESO-1-specific CD8+ and CD4+ T cells, as a measure of T cell activation, was to be determined by FACS analysis. In addition, humoral immunity was to be determined by the presence of NY-ESO-1-specific antibodies which were to be assessed in all patients by ELISA. Disease status was to be assessed at baseline and 2-4 weeks after the fourth vaccination in patients with evaluable (measurable and non-measurable) disease.

Conditions

Tumors

Keywords

NY-ESO-1; Vaccine; Adjuvant or metastatic setting; Several tumor types eligible

Outcome Measures

Primary Outcomes (2)

• Number of Subjects Reporting Adverse Events (AEs) and Dose-limiting Toxicities (DLTs)

  All AEs occurring during the study were documented in the source records and on the respective AE case report form (CRF) pages, regardless of the assumption of a causal relationship. All events that occurred after the first administration of study drug were to be documented. The severity of an AE was assessed according to the NCI CTCAE scale (Version 3.0). DLT was defined as ≥ Grade 3 hematological and non-hematological toxicities or ≥ Grade 2 allergic reaction for generalized urticaria that was definitely, probably, or possibly related to the administration of the NY-ESO-1 protein vaccine.

  up to 14 weeks

• Number of Subjects With NY-ESO-1-Specific Humoral Immunity as Determined by an Increase in Antibody Titer From Baseline.

  Blood samples were taken at baseline and in weeks 2, 4, 5, 7, 8, 10, 11, and 12-14 for the assessment of NY-ESO-1-specific antibodies by an enzyme-linked immunosorbent assay (ELISA). Sera were assessed over a range of dilutions from 1/100 to 1/100,000. Titers were calculated as the serum dilution giving 50% of maximal optical density obtained by using a standard positive serum. Positive results were reciprocal serum titers greater than 100.

  Up to 14 weeks

Secondary Outcomes (3)

• Number of Subjects With Tumor Responses as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST)

  up to 18 weeks

• Number of Subjects With NY-ESO-1 Specific Cellular Immunity as Measured by an Increase in NY-ESO-1-Specific CD4+ T Cells After in Vitro Stimulation

  up to 32 weeks

• Number of Subjects With NY-ESO-1-Specific Cellular Immunity as Measured by an Increase in NY-ESO--Specific CD8+ T Cells After in Vitro Stimulation

  up to 32 weeks

Study Arms (2)

Arm A; 100 μg NY-ESO-1 protein co-mixed with CpG 7909 and Montanide ISA-51 VG

EXPERIMENTAL

100 μg NY-ESO-1 protein co-mixed with 2.5 mg CpG 7909 and 1.25 mL Montanide ISA-51 VG. The vaccine was administered subcutaneously every 3 weeks for a total of 4 doses (study weeks 1, 4, 7 and 10).

Biological: NY-ESO-1 Protein Vaccine

Arm B; 400 μg NY-ESO-1 protein co-mixed with CpG 7909 and Montanide ISA-51 VG

EXPERIMENTAL

400 μg NY-ESO-1 protein co-mixed with 2.5 mg CpG 7909 and 1.25 mL Montanide ISA-51 VG. The vaccine was administered subcutaneously every 3 weeks for a total of 4 doses (study weeks 1, 4, 7 and 10).

Biological: NY-ESO-1 Protein Vaccine

Interventions

NY-ESO-1 Protein Vaccine BIOLOGICAL

NY-ESO-1 recombinant protein mixed with CpG 7909 and Montanide ISA-51 VG

Arm A; 100 μg NY-ESO-1 protein co-mixed with CpG 7909 and Montanide ISA-51 VG; Arm B; 400 μg NY-ESO-1 protein co-mixed with CpG 7909 and Montanide ISA-51 VG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological diagnosis of hepatocellular carcinoma, bladder cancer, breast cancer, non-small lung cancer (NSCLC), melanoma, sarcoma, prostate cancer, esophageal cancer, or ovarian cancer, independent of NY-ESO-1 expression in a tumor biopsy.
• Histological diagnosis of other types of cancers, provided NY-ESO-1 or LAGE-1 expression can be shown in a tumor biopsy.
• At least 4 weeks since surgery prior to first dosing of study agent.
• Laboratory values within the following limits:
• Hemoglobin ≥ 11.0 g/dL
• Neutrophil count ≥ 1.5 x l0\^9/L
• Lymphocyte count ≥ lower limit of institutional normal
• Platelet count ≥ 80 x l0\^9/L
• Serum creatinine ≤ 2.0 mg/dL
• Serum bilirubin ≤ 2 x upper limit of institutional normal
• AST/ALT ≤ 2 x upper limit of institutional normal
• Patients must have a Karnofsky performance status of ≥70%.
• Life expectancy ≥ 6 months.
• Age ≥ 18 years.
• Able and willing to give witnessed, written informed consent for participation in the trial.

You may not qualify if:

• Clinically significant heart disease (i.e. NYHA class 3 congestive heart failure; myocardial infarction within the past six months; unstable angina; coronary angioplasty within the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias).
• Other serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders.
• Previous bone marrow or stem cell transplant.
• History of immunodeficiency disease or autoimmune disease except vitiligo.
• Metastatic disease to the central nervous system, unless treated and stable.
• Other malignancy within 3 years prior to entry into the study, except for treated early-stage melanoma or non-melanoma skin cancer, or cervical carcinoma in situ.
• Known HIV, Hepatitis B or Hepatitis C positivity.
• Chemotherapy, radiation therapy or immunotherapy within 4 weeks prior to first dose of study agent (6 weeks for nitrosoureas).
• Concomitant treatment with steroids. Topical or inhalational steroids are permitted.
• Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dose of study agent.
• Pregnancy or lactation.
• Women of childbearing potential not using a medically acceptable means of contraception.
• Psychiatric or addictive disorders that may compromise the ability to give informed consent.
• Lack of availability of the patient for immunological and clinical follow-up assessment.

Sponsors & Collaborators

• Ludwig Institute for Cancer Research: lead
• NYU Langone Health: collaborator

Study Sites (2)

NYU Clinical Cancer Center

New York, New York, 10016, United States

Location

NY Presbyterian- Columbia

New York, New York, 10032, United States

Location

Related Publications (2)

• Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.

  PMID: 10655437 BACKGROUND

• Valmori D, Souleimanian NE, Tosello V, Bhardwaj N, Adams S, O'Neill D, Pavlick A, Escalon JB, Cruz CM, Angiulli A, Angiulli F, Mears G, Vogel SM, Pan L, Jungbluth AA, Hoffmann EW, Venhaus R, Ritter G, Old LJ, Ayyoub M. Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-priming. Proc Natl Acad Sci U S A. 2007 May 22;104(21):8947-52. doi: 10.1073/pnas.0703395104. Epub 2007 May 15.

  PMID: 17517626 RESULT

MeSH Terms

Conditions

Neoplasms

Results Point of Contact

• Title: Jonathan Skipper PhD
• Organization: Ludwig Institute for Cancer Research

jskipper@lcr.org

12124501539

Study Officials

• Nina Bhardwaj, MD, PhD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

• Sylvia Adams, MD

  NYU Langone Health

  STUDY DIRECTOR

• Gregory Mears, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2006
• First Posted: March 7, 2006
• Study Start: March 21, 2006
• Primary Completion: October 10, 2006
• Study Completion: January 10, 2014
• Last Updated: October 10, 2022
• Results First Posted: November 26, 2021

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)