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

Sponsor

Celldex Therapeutics (Industry)

Overall Status

Terminated

CT.gov ID

NCT02413827

Collaborator

(none)

Enrollment

Locations

Arms

19.3

Actual Duration (Months)

1.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Unresectable Stage III or Stage IV Melanoma	Drug: Combination of varlilumab and ipilimumab Drug: Cohort A: varlilumab & ipilimumab; Cohort B: varlilumab, ipilimumab, CDX-1401 & poly-ICLC	Phase 1/Phase 2

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

Study Type:

Interventional

Actual Enrollment :

9 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 1, 2015

Actual Primary Completion Date :

Nov 2, 2016

Actual Study Completion Date :

Nov 9, 2016

Arms and Interventions

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.

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.

Outcome Measures

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. [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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	California Pacific Medical Center Research Institute	San Francisco	California	United States	94115
2	Sutter Pacific Medical Foundation	Santa Rosa	California	United States	95403
3	University of Colorado	Aurora	Colorado	United States	80045
4	Georgetown University School of Medicine	Washington DC	District of Columbia	United States	20007
5	University of Chicago	Chicago	Illinois	United States	60637
6	Washington University School of Medicine	St. Louis	Missouri	United States	63110
7	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15232
8	Tennessee Oncology Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203