A Study of Varlilumab (Anti-CD27) and Ipilimumab and CDX-1401 in Patients With Unresectable Stage III or IV Melanoma

April 6, 2017 updated by: Celldex Therapeutics

A Phase 1 Safety Pilot/Phase II, Open-label Study of Varlilumab (CDX-1127) in Combination With Ipilimumab and CDX-1401 in Patients With Unresectable Stage III or Stage IV Melanoma

This is a study to determine the clinical benefit (how well the drug works), safety and tolerability of combining a) varlilumab and ipilimumab and b) varlilumab, ipilimumab, CDX-1401 and poly-ICLC. The study will enroll patients with unresectable Stage III or Stage IV melanoma.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Varlilumab is a fully human monoclonal antibody that binds to a molecule called CD27 found on certain immune cells and may act to promote anti-tumor effects.

Yervoy™ (Ipilimumab) is a human monoclonal antibody that blocks CTLA-4, a protein receptor that downregulates the immune system.

CDX-1401 is a vaccine made of a fully human monoclonal antibody linked to NY-ESO-1 and is designed to deliver NY-ESO-1 to professional antigen presenting cells for generating robust immune responses against cancer cells expressing NY-ESO-1. CDX-1401 is administered with poly-ICLC, an adjuvant that enhances vaccine-induced immune responses.

This study will evaluate the safety, tolerability and efficacy of varlilumab and ipilimumab, with or without the addition of CDX-1401/poly-ICLC, in patients with melanoma.

Eligible patients that enroll in the Phase I portion of the study will be assigned to one of two possible dose levels of varlilumab in combination with 3 mg/kg ipilimumab. The first phase of the study will test the safety profile of the combination and determine which dose of varlilumab will be studied in Phase II of the study.

During Phase II, up to 48 patients whose tumors do not express NY-ESO-1, will receive the recommended dose of varlilumab determined from Phase I with 3 mg/kg ipilimumab. Up to 24 patients whose tumors express NY-ESO-1 will receive the recommended dose of varlilumab combined with 3 mg/kg ipilimumab and 1 mg CDX-1401 along with 2 mg poly-ICLC.

All patients enrolled in the study will be closely monitored to determine if there is a response to the treatment as well as for any side effects that may occur.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94115
        • California Pacific Medical Center Research Institute
      • Santa Rosa, California, United States, 95403
        • Sutter Pacific Medical Foundation
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado
    • District of Columbia
      • Washington DC, District of Columbia, United States, 20007
        • Georgetown University School of Medicine
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Medical Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology Sarah Cannon Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  1. Histologic diagnosis of melanoma.
  2. Unresectable Stage III or IV disease
  3. Documented progressive disease based on radiographic, clinical or pathologic assessment.
  4. No more than three prior anticancer regimens (BRAF/MEK inhibitors, IL-2 or investigational agents) including no more than one chemotherapy-containing regimen for advanced (recurrent, locally advanced or metastic) disease.
  5. Measurable disease.
  6. Life expectancy ≥ 12 weeks.
  7. If of childbearing potential (male or female), agrees to practice an effective form of contraception during study treatment and for at least 70 days following last treatment.
  8. Availability of tumor tissue for central laboratory analyses.

Key Exclusion Criteria:

  1. Previous treatment with anti-CD27 antibody, ipilimumab or other anti-CTLA-4 targeted therapies. Previous therapy with other checkpoint blockers such as anti-PD-1 or anti-PD-L1 is acceptable, unless treatment was discontinued for intolerance.
  2. For patients enrolled to Phase II Cohort B: Previous administration of vaccine therapy targeting NY-ESO-1.
  3. BRAF/MEK inhibitors within 2 weeks prior to first dose of study treatment.
  4. Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to first dose of study treatment.
  5. Monoclonal based therapies within 4 weeks and all other immunotherapy within 2 weeks prior to first dose of study treatment.
  6. Systemic radiation therapy within 4 weeks, focal radiotherapy within 2 weeks and radiopharmaceuticals (strontium, samarium) within 8 weeks prior to first dose of study treatment.
  7. Ocular Melanoma
  8. Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancers; or any other cancer from which the patient has been disease-free for at least 3 years.
  9. Active, untreated central nervous system metastases.
  10. Active autoimmune disease or documented history of autoimmune disease.
  11. Active diverticulitis
  12. Significant cardiovascular disease including CHF or poorly controlled hypertension.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase l: varlilumab and ipilimumab
Drug: Combination of varlilumab and ipilimumab

Eligible patients will receive assigned treatments once every 3 weeks for a total of 4 treatments.

Phase l dose: The planned dose of varlilumab will be dependent on the cohort assigned at enrollment. Varlilumab doses are 0.3 mg/kg or 3 mg/kg. Ipilimumab dose is 3 mg/kg.
Experimental: Phase ll: varlilumab & ipilimumab, +/- CDX-1401 & poly-ICLC.
Drug: Cohort A: varlilumab & ipilimumab; Cohort B: varlilumab, ipilimumab, CDX-1401 & poly-ICLC

Eligible patients will receive assigned treatments once every 3 weeks for a total of 4 treatments.

Phase ll dose: The planned dose of varlilumab will be established from Phase I. Ipilimumab dose is 3 mg/kg. Patients assigned to receive CDX-1401 will receive a dose of 1 mg along with 2 mg poly-ICLC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Phase l: Safety and tolerability of varlilumab in combination with ipilimumab as measured by incidences of drug related adverse events (AEs), serious drug related AEs, dose-limiting toxicities and laboratory test abnormalities.
Time Frame: Safety follow-up is 70 days from last study drug dose.
Safety follow-up is 70 days from last study drug dose.
Phase ll: The objective response rate (ORR) is defined as the proportion of patients who achieve radiographic partial or complete response (PR or CR) according to the mWHO tumor response criteria.
Time Frame: Up to 24 weeks
Up to 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Celldex Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2015

Primary Completion (Actual)

November 2, 2016

Study Completion (Actual)

November 9, 2016

Study Registration Dates

First Submitted

March 25, 2015

First Submitted That Met QC Criteria

April 9, 2015

First Posted (Estimate)

April 10, 2015

Study Record Updates

Last Update Posted (Actual)

April 7, 2017

Last Update Submitted That Met QC Criteria

April 6, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDX1127-03

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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