Back to resultsA Study of Varlilumab (Anti-CD27) and Ipilimumab and CDX-1401 in Patients With Unresectable Stage III or IV Melanoma
Primary Purpose
Unresectable Stage III or Stage IV Melanoma
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Combination of varlilumab and ipilimumab
Cohort A: varlilumab & ipilimumab; Cohort B: varlilumab, ipilimumab, CDX-1401 & poly-ICLC
Sponsored by
About this trial
This is an interventional treatment trial for Unresectable Stage III or Stage IV Melanoma focused on measuring Yervoy™, CDX-1401
Eligibility Criteria
Key Inclusion Criteria:
- Histologic diagnosis of melanoma.
- Unresectable Stage III or IV disease
- Documented progressive disease based on radiographic, clinical or pathologic assessment.
- 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.
- Measurable disease.
- Life expectancy ≥ 12 weeks.
- 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.
- Availability of tumor tissue for central laboratory analyses.
Key Exclusion Criteria:
- 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.
- For patients enrolled to Phase II Cohort B: Previous administration of vaccine therapy targeting NY-ESO-1.
- BRAF/MEK inhibitors within 2 weeks prior to first dose of study treatment.
- Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to first dose of study treatment.
- Monoclonal based therapies within 4 weeks and all other immunotherapy within 2 weeks prior to first dose of study treatment.
- 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.
- Ocular Melanoma
- 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.
- Active, untreated central nervous system metastases.
- Active autoimmune disease or documented history of autoimmune disease.
- Active diverticulitis
- Significant cardiovascular disease including CHF or poorly controlled hypertension.
Sites / Locations
- California Pacific Medical Center Research Institute
- Sutter Pacific Medical Foundation
- University of Colorado
- Georgetown University School of Medicine
- University of Chicago
- Washington University School of Medicine
- University of Pittsburgh Medical Center
- Tennessee Oncology Sarah Cannon Research Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Phase l: varlilumab and ipilimumab
Phase ll: varlilumab & ipilimumab, +/- CDX-1401 & poly-ICLC.
Arm Description
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02413827
Brief Title
A Study of Varlilumab (Anti-CD27) and Ipilimumab and CDX-1401 in Patients With Unresectable Stage III or IV Melanoma
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Terminated
Why Stopped
Feasibility concerns due to changes in standard of care
Study Start Date
April 2015 (Actual)
Primary Completion Date
November 2, 2016 (Actual)
Study Completion Date
November 9, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celldex Therapeutics
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Unresectable Stage III or Stage IV Melanoma
Keywords
Yervoy™, CDX-1401
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase l: varlilumab and ipilimumab
Arm Type
Experimental
Arm Title
Phase ll: varlilumab & ipilimumab, +/- CDX-1401 & poly-ICLC.
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Combination of varlilumab and ipilimumab
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cohort A: varlilumab & ipilimumab; Cohort B: varlilumab, ipilimumab, CDX-1401 & poly-ICLC
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Histologic diagnosis of melanoma.
Unresectable Stage III or IV disease
Documented progressive disease based on radiographic, clinical or pathologic assessment.
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.
Measurable disease.
Life expectancy ≥ 12 weeks.
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.
Availability of tumor tissue for central laboratory analyses.
Key Exclusion Criteria:
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.
For patients enrolled to Phase II Cohort B: Previous administration of vaccine therapy targeting NY-ESO-1.
BRAF/MEK inhibitors within 2 weeks prior to first dose of study treatment.
Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to first dose of study treatment.
Monoclonal based therapies within 4 weeks and all other immunotherapy within 2 weeks prior to first dose of study treatment.
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.
Ocular Melanoma
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.
Active, untreated central nervous system metastases.
Active autoimmune disease or documented history of autoimmune disease.
Active diverticulitis
Significant cardiovascular disease including CHF or poorly controlled hypertension.
Facility Information:
Facility Name
California Pacific Medical Center Research Institute
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Sutter Pacific Medical Foundation
City
Santa Rosa
State/Province
California
ZIP/Postal Code
95403
Country
United States
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Georgetown University School of Medicine
City
Washington DC
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Washington University School of Medicine
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Tennessee Oncology Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study of Varlilumab (Anti-CD27) and Ipilimumab and CDX-1401 in Patients With Unresectable Stage III or IV Melanoma
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