Unresectable Stage III or Stage IV MelanomaPhase 1/2NCT02413827
A Study of Varlilumab (Anti-CD27) and Ipilimumab and CDX-1401 in Patients With Unresectable Stage III or IV Melanoma
A Phase 1/2 study testing Combination of varlilumab and ipilimumab and Cohort A: varlilumab & ipilimumab; Cohort B: varlilumab, ipilimumab, CDX-1401 & poly-ICLC in people with Unresectable Stage III or Stage IV Melanoma, run by Celldex Therapeutics at 8 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unresectable Stage III or Stage IV Melanoma
- What is being tested?
- Combination of varlilumab and ipilimumab and Cohort A: varlilumab & ipilimumab; Cohort B: varlilumab, ipilimumab, CDX-1401 & poly-ICLC
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 8 sitesUnited States
- Study dates
- Apr 2015to 9 Nov 2016
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Colorado
Aurora, Colorado, 80045
University of Chicago
Chicago, Illinois, 60637
Tennessee Oncology Sarah Cannon Research Institute
Nashville, Tennessee, 37203
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232
California Pacific Medical Center Research Institute
San Francisco, California, 94115
Sutter Pacific Medical Foundation
Santa Rosa, California, 95403
Washington University School of Medicine
St Louis, Missouri, 63110
Georgetown University School of Medicine
Washington D.C., District of Columbia, 20007
About this study
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
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.
Read the 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.
- Being tested
- Combination of varlilumab and ipilimumab, Cohort A: varlilumab & ipilimumab; Cohort B: varlilumab, ipilimumab, CDX-1401 & poly-ICLC
- Keywords
- Yervoy™, CDX-1401
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combination of varlilumab and ipilimumabDrug
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.
Cohort A: varlilumab & ipilimumab; Cohort B: varlilumab, ipilimumab, CDX-1401 & poly-ICLCDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Phase l: varlilumab and ipilimumab | Experimental | Not described Receives: Drug: Combination of varlilumab and ipilimumab |
| Phase ll: varlilumab & ipilimumab, +/- CDX-1401 & poly-ICLC. | Experimental | Not described Receives: Drug: Cohort A: varlilumab & ipilimumab; Cohort B: varlilumab, ipilimumab, CDX-1401 & poly-ICLC |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2015 (estimated)
- Study startApr 2015
- Primary completion2 Nov 2016
- Study completion9 Nov 2016
Why it stopped: Feasibility concerns due to changes in standard of care
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unresectable Stage III or Stage IV MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celldex Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02413827
- Sponsor's protocol ID
- CDX1127-03
- Status last verified
- Apr 2017
- First submitted
- 25 Mar 2015
- Last updated
- 7 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02413827
- Acronym / sponsor ID
- CDX1127-03
- Keywords
- Yervoy™, CDX-1401
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Feasibility concerns due to changes in standard of care
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Celldex TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Apr 2015 (actual)
- Primary completion
- 2 Nov 2016 (actual)
- Study completion
- 9 Nov 2016 (actual)
- First posted
- 10 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase l: varlilumab and ipilimumab | Experimental | Drug: Combination of varlilumab and ipilimumab |
| Phase ll: varlilumab & ipilimumab, +/- CDX-1401 & poly-ICLC. | Experimental | Drug: Cohort A: varlilumab & ipilimumab; Cohort B: varlilumab, ipilimumab, CDX-1401 & poly-ICLC |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Combination of varlilumab and ipilimumabEligible 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. | Drug | Phase l: varlilumab and ipilimumab |
| Cohort A: varlilumab & ipilimumab; Cohort B: varlilumab, ipilimumab, CDX-1401 & poly-ICLCEligible 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. | Drug | Phase ll: varlilumab & ipilimumab, +/- CDX-1401 & poly-ICLC. |
Primary outcome
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.
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
Results and safety
The study was stopped early (reason given: Feasibility concerns due to changes in standard of care). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Combination of varlilumab and ipilimumab and Cohort A: varlilumab & ipilimumab; Cohort B: varlilumab, ipilimumab, CDX-1401 & poly-ICLC in people with Unresectable Stage III or Stage IV Melanoma, run by Celldex Therapeutics at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Feasibility concerns due to changes in standard of care). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2017.