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

NCT02413827 | Terminated Phase 1 DMC

• 1 other identifier: CDX1127-03
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 8

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.

Conditions

Unresectable Stage III or Stage IV Melanoma

Keywords

Yervoy™, CDX-1401

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Up to 24 weeks

Study Arms (2)

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

Interventions

Combination of varlilumab and ipilimumab 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 l: varlilumab and ipilimumab

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

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

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Celldex Therapeutics: lead

Study Sites (8)

California Pacific Medical Center Research Institute

San Francisco, California, 94115, United States

Location

Sutter Pacific Medical Foundation

Santa Rosa, California, 95403, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Georgetown University School of Medicine

Washington D.C., District of Columbia, 20007, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Tennessee Oncology Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab; poly ICLC

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; 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

Study Design

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

Study Record Dates

• First Submitted: March 25, 2015
• First Posted: April 10, 2015
• Study Start: April 1, 2015
• Primary Completion: November 2, 2016
• Study Completion: November 9, 2016
• Last Updated: April 7, 2017

Record last verified: 2017-04

Locations

US (8)