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

NCT01810016 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: LUD2012-004
• Study Type: interventional
• Target: 8
• Locations: 2 countries
• Sites: 5

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.

Conditions

Unresectable or Metastatic Melanoma

Keywords

NY-ESO-1; Metastatic Melanoma; Ipilimumab; Phase I; Adjuvant; Immunologic; Vaccination; Immunotherapy; Neoplasm

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Treatment-emergent Adverse Events

  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.

  Continuously for up to 6 months

Secondary Outcomes (1)

• Number of Patients With Immune-related Tumor Response at the Last Assessment

  Up to 5 months

Study Arms (3)

Arm A

EXPERIMENTAL

Ipilimumab (IV) followed by NY-ESO-1 recombinant protein mixed with Poly-ICLC and Montanide (SC) every 3 weeks for 4 doses.

Biological: Ipilimumab; Biological: NY-ESO-1 Protein Vaccine

Arm B

EXPERIMENTAL

Ipilimumab (IV) followed by NY-ESO-1 OLP4 mixed with Poly-ICLC and Montanide (SC) every 3 weeks for 4 doses.

Biological: Ipilimumab; Biological: NY-ESO-1 OLP4 Vaccine with Poly-ICLC and Montanide

Arm C

EXPERIMENTAL

Ipilimumab (IV) followed by NY-ESO-1 OLP4 mixed with Poly-ICLC (SC) every 3 weeks for 4 doses.

Biological: Ipilimumab; Biological: NY-ESO-1 OLP4 Vaccine with Poly-ICLC

Interventions

Ipilimumab BIOLOGICAL

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.

Also known as: Yervoy

Arm A; Arm B; Arm C

NY-ESO-1 Protein Vaccine BIOLOGICAL

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.

Arm A

NY-ESO-1 OLP4 Vaccine with Poly-ICLC and Montanide BIOLOGICAL

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.

Arm B

NY-ESO-1 OLP4 Vaccine with Poly-ICLC BIOLOGICAL

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.

Arm C

Eligibility Criteria

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

You may qualify if:

• 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).
• Radiologically measurable disease by irRC.
• 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.
• Willingness to provide at least one pre-and post-vaccination tumor biopsy sample.
• Expected survival of at least 4 months.
• At the time of Day 1 of the study, patients must have been at least 3 weeks since surgery.
• 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).
• Eastern Cooperative Oncology Group performance status of 0 to 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);

You may not qualify if:

• Any contraindications for ipilimumab/Yervoy® as per package insert (applicable for US sites) or product information (applicable for Australia site).
• Prior exposure to NY-ESO-1 vaccine.
• 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).
• Unresolved immune-related adverse events following prior biological therapy.
• Systemic treatment with high-dose corticosteroids (greater than prednisone 10 mg daily or equivalent).
• Treatment with protocol-specified non-permitted concomitant therapies.
• Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may have been available.
• 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.
• Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
• Known immunodeficiency or human immunodeficiency virus positivity, active Hepatitis B or active Hepatitis C.
• History of severe allergic reactions to vaccines or unknown allergens.
• Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders).
• Participation in any other clinical trial involving another investigational agent within 4 weeks prior to Day 1 of the study.
• Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.
• Lack of availability for immunological and clinical follow-up assessments.

Sponsors & Collaborators

• Ludwig Institute for Cancer Research: lead
• Cancer Research Institute, NY, USA: collaborator

Study Sites (5)

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Pittsburgh Cancer Center

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Austin Health, Ludwig Oncology Unit

Melbourne, Victoria, Australia

Location

MeSH Terms

Conditions

Melanoma; Neoplasms

Interventions

Ipilimumab; poly ICLC; Monatide (IMS 3015)

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and 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.

Results Point of Contact

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

jskipper@lcr.org

(212) 450-1539

Study Officials

• Michael A Postow, MD

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: March 8, 2013
• First Posted: March 13, 2013
• Study Start: January 24, 2014
• Primary Completion: May 17, 2016
• Study Completion: May 17, 2016
• Last Updated: October 12, 2022
• Results First Posted: November 30, 2018

Record last verified: 2022-10

Locations

US (4); AU (1)