A Vaccine (CDX-1401) With or Without a Biologic Drug (CDX-301) for the Treatment of Patients With Stage IIB-IV Melanoma

NCT02129075 | Completed Phase 2 Results FDA Drug

• 4 other identifiers: NCI-2014-00898CITN-07-FLT3LP30CA015704U01CA154967
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 7

Brief Summary

This phase II trial studies the effect of a vaccine called CDX-1401 given with or without a biologic drug called CDX-301 in treating patients with stage IIB-IV melanoma. The cancer vaccine CDX-1401 attaches to a protein that is made in tumor cells. The vaccine helps the body recognize the tumor to fight the cancer. The biologic drug CDX-301 may help the body make more of the tumor fighting cells, known as dendritic cells. Another biologic drug, poly-ICLC, may stimulate the immune system and help these dendritic cells mature so that they can recognize the tumor. Giving CDX-301 may make the immune response to a combination of CDX-1401 and poly-ICLC better.

Conditions

Cutaneous Melanoma; Melanoma; Melanoma of Unknown Primary; Mucosal Melanoma; Ocular Melanoma; Stage IIB Cutaneous Melanoma AJCC v6 and v7; Stage IIC Cutaneous Melanoma AJCC v6 and v7; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

Outcome Measures

Primary Outcomes (1)

• Immune T-cell Response to NY-ESO-1

  Response rates will be analyzed by tabulating the frequency of positive response for each assay by antigen and treatment arm at each time point for which an assessment is performed. Response rates will be presented with their corresponding 95% confidence interval estimates calculated using the score test method. Fisher's exact tests will be used to compare cohort 1 and cohort 2 at the peak time point, with a significant difference declared if the 1-sided P value is =\< 0.10.

  At 12 weeks after final vaccination

Secondary Outcomes (4)

• T Cell Responses to Other Ongoing and Nascent Antitumor Response Antigens Associated With Melanoma (e.g. PRAME, MAGE-A3, p53, and gp1000) as Well as Memory and Chronic Viral Responses (CMV, EBV)

  Up to 12 weeks after final vaccination

• Frequency and Phenotypic Character of PBMC Subsets Including DCs, Monocyte Populations, T Cells, and NK Cells - Highest Peak Fold Change Over Baseline (Log 2 Fold)

  Up to 12 weeks after final vaccination

• Tumor Recurrence

  Up to 600 days from first vaccine

• Overall Survival

  Up to 1 year after patient's 12 week visit

Study Arms (2)

Arm I (CDX-301, CDX-1401, poly-ICLC)

EXPERIMENTAL

Patients receive recombinant Flt3 ligand (CDX-301) SC on days -7 to -1, 1-3, and 22-28 of cycle 1 and only on days 1-3 of cycle 2. Patients also receive CDX-1401 SC or ID on day 1 of each cycle and poly-ICLC SC on days 1-2 of each cycle. Treatment repeats every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401; Drug: Poly ICLC; Biological: Recombinant Flt3 Ligand

Arm II (CDX-1401, poly-ICLC)

ACTIVE COMPARATOR

Patients receive CDX-1401 and poly-ICLC as in Arm I. Treatment repeats every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401; Drug: Poly ICLC

Interventions

DEC-205/NY-ESO-1 Fusion Protein CDX-1401 BIOLOGICAL

Given SC or ID

Also known as: CDX-1401

Arm I (CDX-301, CDX-1401, poly-ICLC); Arm II (CDX-1401, poly-ICLC)

Poly ICLC DRUG

Given SC

Also known as: Hiltonol, Poly I:Poly C with Poly-L-Lysine Stabilizer, poly-ICLC, PolyI:PolyC with Poly-L-Lysine Stabilizer, Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose, Polyriboinosinic-Polyribocytidylic Acid-Polylysine Carboxymethylcellulose, Stabilized Polyriboinosinic/Polyribocytidylic Acid

Arm I (CDX-301, CDX-1401, poly-ICLC); Arm II (CDX-1401, poly-ICLC)

Recombinant Flt3 Ligand BIOLOGICAL

Given SC

Also known as: CDX-301, FLT 3 Ligand, FLT3 Ligand, Flt3-Ligand, Flt3L, Mobist, Mobista, rhuFlt3L

Arm I (CDX-301, 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:

• Patients with fully resected stage IIb through IV melanoma, with melanoma validated by histology or cytology, who have NOT received prior therapy.
• Patients may have had primary cutaneous, mucosal, or ocular melanoma or metastasis from an unknown primary site.
• Tissue should be submitted for evaluation of NY-ESO-1 expression and T-cell infiltrates. However, availability of tissue and/or positivity for NY-ESO-1 is not mandatory.
• Prior radiation, chemotherapy or biologics NOT allowed
• Not currently receiving any anticancer therapy
• Age \>= 18 years
• Because no dosing or adverse event (AE) data are currently available on the use of CDX-1401 or CDX-301 in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• Eastern Cooperative Oncology Group (ECOG) performance score of 0-1
• Life expectancy of at least 6 months
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,000/mcL
• Platelets \>= 75,000/mcL
• Hemoglobin \> 9 g/dL
• Total bilirubin \< 1.5 x institutional upper limit of normal (bilirubin \< 3 x institutional upper limit of normal for Gilbert's syndrome)
• Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal

You may not qualify if:

• Patients who have had cytotoxic chemotherapy, radiotherapy, interferon (IFN), or ipilimumab before entering the study
• Immunosuppressive therapy within 30 days prior to initiation of protocol therapy
• Steroid therapy, or steroid therapy with more than 7 consecutive days of steroids within the prior 4 weeks
• The use of prednisone or equivalent \< 0.125 mg/kg/day (absolute maximum of 10 mg/day) as replacement therapy is permitted
• Inhaled or topical corticosteroids are permitted
• Patients who are receiving any other investigational agents
• Current or history of systemic autoimmune disease requiring systemic therapy.
• The presence of laboratory evidence of autoimmune disease (e.g., positive antinuclear antibody \[ANA\] titer) without associated symptoms
• Clinical evidence of vitiligo
• Other forms of depigmenting illness
• Cardiovascular disease that meets one of the following: congestive heart failure (New York Heart Association Class III or IV), active angina pectoris, or recent myocardial infarction (within the last 6 months)
• Cirrhosis or chronic hepatitis C virus positivity or chronic hepatitis B infection
• Known history of immunodeficiency disorder other than HIV-positive status
• Extensive active brain disease including symptomatic brain metastases or presence of leptomeningeal disease
• NOTE: Patients with brain metastasis, after definitive therapy with surgery or stereotactic radiation and stable off steroids for \>= 4 weeks, are eligible

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (7)

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Bhardwaj N, Friedlander PA, Pavlick AC, Ernstoff MS, Gastman BR, Hanks BA, Curti BD, Albertini MR, Luke JJ, Blazquez AB, Balan S, Bedognetti D, Beechem JM, Crocker AS, D'Amico L, Danaher P, Davis TA, Hawthorne T, Hess BW, Keler T, Lundgren L, Morishima C, Ramchurren N, Rinchai D, Salazar AM, Salim BA, Sharon E, Vitale LA, Wang E, Warren S, Yellin MJ, Disis ML, Cheever MA, Fling SP. Flt3 ligand augments immune responses to anti-DEC-205-NY-ESO-1 vaccine through expansion of dendritic cell subsets. Nat Cancer. 2020 Dec;1(12):1204-1217. doi: 10.1038/s43018-020-00143-y. Epub 2020 Nov 16.

  PMID: 35121932 DERIVED

MeSH Terms

Conditions

Melanoma; Uveal Melanoma

Interventions

poly ICLC; flt3 ligand protein

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; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases

Results Point of Contact

• Title: Dr. Martin A. Cheever
• Organization: Fred Hutchinson Cancer Research Center

mcheever@fredhutch.org

206-667-4141

Study Officials

• Nina Bhardwaj

  Cancer Immunotherapy Trials Network

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2014
• First Posted: May 2, 2014
• Study Start: April 9, 2014
• Primary Completion: March 28, 2016
• Study Completion: May 18, 2018
• Last Updated: November 16, 2021
• Results First Posted: November 16, 2021

Record last verified: 2021-11

Locations

US (7)