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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-04-30

Study Completion Date

2016-11-09

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Combination of Anti-CD137 & Ipilimumab in Patients With Melanoma

NCT00803374

Melanoma

WITHDRAWN PHASE1

Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of Investigational Treatments in Combination With Standard of Care Immune Checkpoint Inhibitors in Participants With Advanced Melanoma

NCT02723006

Melanoma

TERMINATED PHASE1

A Phase 1b Open Label, Dose Escalation Study of PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma

NCT01826448

V600-mutated BRAF Unresectable Melanoma V600-mutated BRAF Metastatic Melanoma Stage III or Stage IV Metastatic Melanoma That Has Not Been Previously Treated With a Selective BRAF Inhibitor

TERMINATED PHASE1

Safety and Efficacy of Selinexor in Combination With Pembrolizumab in Recurrent Advanced Melanoma

NCT04768881

Locally Advanced Unresectable or Metastatic Melanoma

TERMINATED PHASE2

Ipilimumab With or Without High-Dose Recombinant Interferon Alfa-2b in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery

NCT01708941

Recurrent Melanoma Stage IIIA Cutaneous Melanoma AJCC v7 Stage IIIB Cutaneous Melanoma AJCC v7 +2 more

ACTIVE_NOT_RECRUITING PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Unresectable Stage III or Stage IV Melanoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Phase l: varlilumab and ipilimumab

Group Type EXPERIMENTAL

Combination of varlilumab and ipilimumab

Intervention Type DRUG

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.

Phase ll: varlilumab & ipilimumab, +/- CDX-1401 & poly-ICLC.

Group Type EXPERIMENTAL

Cohort A: varlilumab & ipilimumab; Cohort B: varlilumab, ipilimumab, CDX-1401 & poly-ICLC

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.

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.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No