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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT02129075
• Collaborator: (none)
• Enrollment: 60
• Locations: 7
• Arms: 2
• Actual Duration (Months): 49.3
• Patients Per Site: 8.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Biological: DEC-205/NY-ESO-1 Fusion Protein CDX-1401; Drug: Poly ICLC; Biological: Recombinant Flt3 Ligand	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

1. To determine whether the immune response to NY-ESO-1 elicited by vaccination with DEC-205/NY-ESO-1 fusion protein CDX-1401 (CDX-1401) plus polyinosinic-polycytidylic acid stabilized with poly-L-lysine and carboxymethylcellulose (poly-ICLC) is substantially increased by prior expansion in the number of circulating dendritic cells (DC) by therapy with recombinant Flt3 ligand (CDX-301) (fms-related tyrosine kinase 3 ligand [Flt3L]).

SECONDARY OBJECTIVES:

1. To assess the effect of the vaccine regimen on immune responses to other ongoing and nascent antitumor response antigens associated with melanoma (e.g., PRAME, MAGE-A3, p53, and gp100) as well as memory viral responses (influenza A) and chronic viral responses (cytomegalovirus [CMV], Epstein-Barr virus [EBV]).

2. To assess the effect of the vaccine regimen on the frequency and phenotypic character of peripheral blood mononuclear cell (PBMC) subsets including DCs, monocyte populations, T cells, and natural killer (NK) cells.

3. To assess the safety, tolerability, and clinical efficacy of the vaccine regimens.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive recombinant Flt3 ligand (CDX-301) subcutaneously (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 intradermally (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.

ARM II: 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.

After completion of study treatment, patients are followed up at 4 and 12 weeks and then annually thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Open-Label, Multicenter, Randomized Study of CDX-1401, a Dendritic Cell Targeting NY-ESO-1 Vaccine, in Patients With Malignant Melanoma Pre-Treated With Recombinant CDX-301, a Recombinant Human Flt3 Ligand
• Actual Study Start Date: Apr 9, 2014
• Actual Primary Completion Date: Mar 28, 2016
• Actual Study Completion Date: May 18, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (CDX-301, CDX-1401, poly-ICLC) 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; Given SC or ID; Other Names: CDX-1401 ; Drug: Poly ICLC; Given SC; Other Names: 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 ; Biological: Recombinant Flt3 Ligand; Given SC; Other Names: CDX-301 FLT 3 Ligand FLT3 Ligand Flt3-Ligand Flt3L Mobist Mobista rhuFlt3L
Active Comparator: Arm II (CDX-1401, poly-ICLC) 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; Given SC or ID; Other Names: CDX-1401 ; Drug: Poly ICLC; Given SC; Other Names: 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

Outcome Measures

Primary Outcome Measures

1. Immune T-cell Response to NY-ESO-1 [At 12 weeks after final vaccination]

   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.

Secondary Outcome Measures

1. 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]

   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.

2. 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]

   Graphical and tabular summaries of the assay data will be made. Linear mixed effects model and possibly weighted generalized estimating equation methods will be considered for a supportive analysis of the longitudinal data over time.

3. Tumor Recurrence [Up to 600 days from first vaccine]

   Time to first recurrence from first vaccine among subjects who have experienced recurrence. (days)

4. Overall Survival [Up to 1 year after patient's 12 week visit]

   Overall survival not assessed

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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

• Creatinine < 1.5 x institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

• The first six patients enrolled in the Flt3L arm of the study cannot be human immunodeficiency virus (HIV)-positive. After the evaluation of safety in the first 6 patients, HIV-positive patients with adequate immune function as evidenced by stable

CD4 counts >= 350/mm^3 are allowed to participate if the following criteria are met:

• maintained on stable antiretroviral therapy with no significant drug interactions, and

• no recent history of acquired immunodeficiency syndrome (AIDS) indicator conditions (> 2 years from enrolling in trial), and

• physician providing patient's care for HIV must also approve of patient entering the study

• Females of childbearing potential must have a negative pregnancy test within 7 days before the initiation of protocol therapy.

• The effects of CDX-1401 or CDX-301 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) before study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception before the study, for the duration of study participation, and 4 months after completion of CDX-1401 or CDX-301 administration.

• NOTE: Subjects are considered not of child-bearing potential if they are surgically sterile, they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy, or they are postmenopausal. Menopause is the age associated with complete cessation of menstrual cycles, menses, and implies the loss of reproductive potential. By a practical definition, it assumes menopause after 1 year without menses with an appropriate clinical profile at the appropriate age.

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• 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.

• NOTE: The following will not be exclusionary:

• 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

• NOTE: A positive hepatitis B serology indicative of previous immunization (i.e., hepatitis B virus surface antibody [HBsAb]-positive and hepatitis B virus core antibody [HBcAb]-negative), or a fully resolved acute hepatitis B virus infection is not an exclusion criterion

• 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

• Other invasive cancers that are clinically active

• Pregnancy or nursing or unwilling to take adequate birth control during therapy

• NOTE: Pregnant women are excluded from this study because CDX-1401 or CDX-301 and poly-ICLC have an unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CDX-1401 or CDX-301, breastfeeding should be discontinued if the mother is treated with CDX-1401 or CDX-301 and poly-ICLC

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to CDX-1401 or CDX-301 or poly-ICLC

• Prior organ allograft or allogeneic transplantation, if the transplanted tissue is still in place

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Medical or psychiatric illness that would, in the opinion of the investigator, preclude participation in the study or the ability of patients to provide informed consent for themselves

• History of pulmonary disease such as emphysema or chronic obstructive pulmonary disease (COPD) (forced expiratory volume in 1 second [FEV1] < 60% of predicted for height and age). Pulmonary function tests (PFTs) are required in patients with prolonged smoking history or symptoms of respiratory dysfunction

• Vaccinations other than those given as part of this research study (with the exception of influenza vaccine) are prohibited throughout the duration of study participation.

• NOTE: Influenza vaccination (inactivated) is permitted during the flu season. The preferred time is 7 to 14 days after CDX-1401 administration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
2	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
3	Mount Sinai Hospital	New York	New York	United States	10029
4	Duke University Medical Center	Durham	North Carolina	United States	27710
5	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
6	Providence Portland Medical Center	Portland	Oregon	United States	97213
7	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Nina Bhardwaj, Cancer Immunotherapy Trials Network

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT02129075
• Other Study ID Numbers: NCI-2014-00898; NCI-2014-00898; CITN-07-FLT3L; CITN-07-FLT3L; CITN-07-FLT3L; P30CA015704; U01CA154967
• First Posted: May 2, 2014
• Last Update Posted: Nov 16, 2021
• Last Verified: Nov 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Melanoma; Skin Neoplasms; Poly I-C; Carboxymethylcellulose Sodium; Poly ICLC; Flt3 ligand protein

Study Results

Participant Flow

Pre-assignment Detail	No enrolled participants were excluded from the study before assignment to groups.

Arm/Group Title	Arm I (CDX-301, CDX-1401, and Poly-ICLC)	Arm II (CDX-1401 and Poly-ICLC)
Arm/Group Description	Patients receive recombinant flt3 ligand (CDX-301) SC on days -7 to -1, 1-3, and 22-28 of course 1 and on days 1-3 of course 2 only; DEC-205/NY-ESO-1 fusion protein CDX-1401 SC or ID on days 1 and 2; and poly-ICLC SC on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. DEC-205/NY-ESO-1 Fusion Protein CDX-1401: Given SC or ID Laboratory Biomarker Analysis: Correlative studies Neoantigen-based Melanoma-Poly-ICLC Vaccine: Given SC Pharmacological Study: Correlative studies Recombinant Flt3 Ligand: Given SC	Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401and poly-ICLC as in Arm I. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. DEC-205/NY-ESO-1 Fusion Protein CDX-1401: Given SC or ID Laboratory Biomarker Analysis: Correlative studies Neoantigen-based Melanoma-Poly-ICLC Vaccine: Given SC Pharmacological Study: Correlative studies
Period Title: Overall Study
STARTED	30	30
COMPLETED	30	30
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm I (CDX-301, CDX-1401, and Poly-ICLC)	Arm II (CDX-1401 and Poly-ICLC)	Total
Arm/Group Description	Patients receive recombinant Flt3 ligand (CDX-301) SC on days -7 to -1, 1-3, and 22-28 of course 1 and on days 1-3 of course 2 only; DEC-205/NY-ESO-1 fusion protein CDX-1401 SC or ID on days 1 and 2; and poly-ICLC SC on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. DEC-205/NY-ESO-1 Fusion Protein CDX-1401: Given SC or ID Laboratory Biomarker Analysis: Correlative studies Neoantigen-based Melanoma-Poly-ICLC Vaccine: Given SC Pharmacological Study: Correlative studies Recombinant Flt3 Ligand: Given SC	Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401and poly-ICLC as in Arm I. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. DEC-205/NY-ESO-1 Fusion Protein CDX-1401: Given SC or ID Laboratory Biomarker Analysis: Correlative studies Neoantigen-based Melanoma-Poly-ICLC Vaccine: Given SC Pharmacological Study: Correlative studies	Total of all reporting groups
Overall Participants	30	30	60
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	22 73.3%	25 83.3%	47 78.3%
>=65 years	8 26.7%	5 16.7%	13 21.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.6 (13.4)	51.6 (14.5)	53.1 (13.9)
Sex: Female, Male (Count of Participants)
Female	10 33.3%	9 30%	19 31.7%
Male	20 66.7%	21 70%	41 68.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 3.3%	1 1.7%
Not Hispanic or Latino	30 100%	28 93.3%	58 96.7%
Unknown or Not Reported	0 0%	1 3.3%	1 1.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 3.3%	1 1.7%
White	30 100%	28 93.3%	58 96.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 3.3%	1 1.7%

Outcome Measures

1. Primary Outcome

Title	Immune T-cell Response to NY-ESO-1
Description	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.
Time Frame	At 12 weeks after final vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (CDX-301, CDX-1401, and Poly-ICLC)	Arm II (CDX-1401 and Poly-ICLC)
Arm/Group Description	Patients receive recombinant Flt3 ligand (CDX-301) SC on days -7 to -1, 1-3, and 22-28 of course 1 and on days 1-3 of course 2 only; DEC-205/NY-ESO-1 fusion protein CDX-1401 SC or ID on days 1 and 2; and poly-ICLC SC on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. DEC-205/NY-ESO-1 Fusion Protein CDX-1401: Given SC or ID Laboratory Biomarker Analysis: Correlative studies Neoantigen-based Melanoma-Poly-ICLC Vaccine: Given SC Pharmacological Study: Correlative studies Recombinant Flt3 Ligand: Given SC	Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401and poly-ICLC as in Arm I. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. DEC-205/NY-ESO-1 Fusion Protein CDX-1401: Given SC or ID Laboratory Biomarker Analysis: Correlative studies Neoantigen-based Melanoma-Poly-ICLC Vaccine: Given SC Pharmacological Study: Correlative studies
Measure Participants	28	26
Count of Participants [Participants]	15 50%	10 33.3%

2. Secondary Outcome

Title	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)
Description	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.
Time Frame	Up to 12 weeks after final vaccination

Outcome Measure Data

Analysis Population Description

T cell responses to MAGE-A3 and PRAME; positive at any timepoint

Arm/Group Title	Arm I (CDX-301, CDX-1401, and Poly-ICLC)	Arm II (CDX-1401 and Poly-ICLC)
Arm/Group Description	Patients receive recombinant flt3 ligand SC on days -7 to -1, 1-3, and 22-28 of course 1 and on days 1-3 of course 2 only; DEC-205/NY-ESO-1 fusion protein CDX-1401 SC or ID on days 1 and 2; and poly-ICLC SC on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. DEC-205/NY-ESO-1 Fusion Protein CDX-1401: Given SC or ID Laboratory Biomarker Analysis: Correlative studies Neoantigen-based Melanoma-Poly-ICLC Vaccine: Given SC Pharmacological Study: Correlative studies Recombinant Flt3 Ligand: Given SC	Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401and poly-ICLC as in Arm I. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. DEC-205/NY-ESO-1 Fusion Protein CDX-1401: Given SC or ID Laboratory Biomarker Analysis: Correlative studies Neoantigen-based Melanoma-Poly-ICLC Vaccine: Given SC Pharmacological Study: Correlative studies
Measure Participants	30	28
Count of Participants [Participants]	7 23.3%	7 23.3%

3. Secondary Outcome

Title	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)
Description	Graphical and tabular summaries of the assay data will be made. Linear mixed effects model and possibly weighted generalized estimating equation methods will be considered for a supportive analysis of the longitudinal data over time.
Time Frame	Up to 12 weeks after final vaccination

Outcome Measure Data

Analysis Population Description

Only a subset of patient specimens were needed to meet statistical power. 15 participants were analyzed in Arm I (CDX-301, CDX-1401, and poly-ICLC and 16 participants were analyzed in Arm II (CDX-1401 and poly-ICLC). One less patient in Arm 1 was analyzed due to sample quality.

Arm/Group Title	Arm I (CDX-301, CDX-1401, and Poly-ICLC)	Arm II (CDX-1401 and Poly-ICLC)
Arm/Group Description	Patients receive recombinant flt3 ligand SC on days -7 to -1, 1-3, and 22-28 of course 1 and on days 1-3 of course 2 only; DEC-205/NY-ESO-1 fusion protein CDX-1401 SC or ID on days 1 and 2; and poly-ICLC SC on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. DEC-205/NY-ESO-1 Fusion Protein CDX-1401: Given SC or ID Laboratory Biomarker Analysis: Correlative studies Neoantigen-based Melanoma-Poly-ICLC Vaccine: Given SC Pharmacological Study: Correlative studies Recombinant Flt3 Ligand: Given SC	Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401and poly-ICLC as in Arm I. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. DEC-205/NY-ESO-1 Fusion Protein CDX-1401: Given SC or ID Laboratory Biomarker Analysis: Correlative studies Neoantigen-based Melanoma-Poly-ICLC Vaccine: Given SC Pharmacological Study: Correlative studies
Measure Participants	15	16
cDCs	30.4 (16.98)	0.9 (0.26)
Monocytes	6.1 (2.11)	1.0 (0.18)
CD4 T cells	1.2 (0.28)	1.1 (0.27)
NK CD56br cells	5.8 (2.84)	1.26 (0.32)
CD8 T cells	1.3 (0.36)	1.0 (.26)
pDC	16.5 (7.27)	0.8 (0.24)

4. Secondary Outcome

Title	Tumor Recurrence
Description	Time to first recurrence from first vaccine among subjects who have experienced recurrence. (days)
Time Frame	Up to 600 days from first vaccine

Outcome Measure Data

Analysis Population Description

Analysis is reported for the number of subjects with recurrence (N=12 Arm I) (N=9 Arm II)

Arm/Group Title	Arm I (CDX-301, CDX-1401, and Poly-ICLC)	Arm II (CDX-1401 and Poly-ICLC)
Arm/Group Description	Patients receive recombinant flt3 ligand SC on days -7 to -1, 1-3, and 22-28 of course 1 and on days 1-3 of course 2 only; DEC-205/NY-ESO-1 fusion protein CDX-1401 SC or ID on days 1 and 2; and poly-ICLC SC on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. DEC-205/NY-ESO-1 Fusion Protein CDX-1401: Given SC or ID Laboratory Biomarker Analysis: Correlative studies Neoantigen-based Melanoma-Poly-ICLC Vaccine: Given SC Pharmacological Study: Correlative studies Recombinant Flt3 Ligand: Given SC	Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401and poly-ICLC as in Arm I. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. DEC-205/NY-ESO-1 Fusion Protein CDX-1401: Given SC or ID Laboratory Biomarker Analysis: Correlative studies Neoantigen-based Melanoma-Poly-ICLC Vaccine: Given SC Pharmacological Study: Correlative studies
Measure Participants	12	9
Mean (Standard Deviation) [days]	360.3 (191.1)	389.2 (223.2)

5. Secondary Outcome

Title	Overall Survival
Description	Overall survival not assessed
Time Frame	Up to 1 year after patient's 12 week visit

Outcome Measure Data

Analysis Population Description

Data not collected

Arm/Group Title	Arm I (CDX-301, CDX-1401, and Poly-ICLC)	Arm II (CDX-1401 and Poly-ICLC)
Arm/Group Description	Patients receive recombinant flt3 ligand (CDX-301) SC on days -7 to -1, 1-3, and 22-28 of course 1 and on days 1-3 of course 2 only; DEC-205/NY-ESO-1 fusion protein CDX-1401 SC or ID on days 1 and 2; and poly-ICLC SC on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. DEC-205/NY-ESO-1 Fusion Protein CDX-1401: Given SC or ID Laboratory Biomarker Analysis: Correlative studies Neoantigen-based Melanoma-Poly-ICLC Vaccine: Given SC Pharmacological Study: Correlative studies Recombinant Flt3 Ligand: Given SC	Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401and poly-ICLC as in Arm I. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. DEC-205/NY-ESO-1 Fusion Protein CDX-1401: Given SC or ID Laboratory Biomarker Analysis: Correlative studies Neoantigen-based Melanoma-Poly-ICLC Vaccine: Given SC Pharmacological Study: Correlative studies
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	Systematic evaluation by clinicaltrials.gov definition
Arm/Group Title	Arm I (CDX-301, CDX-1401, and Poly-ICLC)		Arm II (CDX-1401 and Poly-ICLC)
Arm/Group Description	Patients receive recombinant Flt3 ligand (CDX-301) SC on days -7 to -1, 1-3, and 22-28 of course 1 and on days 1-3 of course 2 only; DEC-205/NY-ESO-1 fusion protein CDX-1401 SC or ID on days 1 and 2; and poly-ICLC SC on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. DEC-205/NY-ESO-1 Fusion Protein CDX-1401: Given SC or ID Laboratory Biomarker Analysis: Correlative studies Neoantigen-based Melanoma-Poly-ICLC Vaccine: Given SC Pharmacological Study: Correlative studies Recombinant Flt3 Ligand: Given SC		Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401and poly-ICLC as in Arm I. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. DEC-205/NY-ESO-1 Fusion Protein CDX-1401: Given SC or ID Laboratory Biomarker Analysis: Correlative studies Neoantigen-based Melanoma-Poly-ICLC Vaccine: Given SC Pharmacological Study: Correlative studies
All Cause Mortality
	Arm I (CDX-301, CDX-1401, and Poly-ICLC)		Arm II (CDX-1401 and Poly-ICLC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (CDX-301, CDX-1401, and Poly-ICLC)		Arm II (CDX-1401 and Poly-ICLC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		4/30 (13.3%)
General disorders
General disorders and administration site conditions	0/30 (0%)	0	1/30 (3.3%)	1
Infections and infestations
Infections and infestations	/30 (NaN)		1/30 (3.3%)	1
Nervous system disorders
Nervous system disorders	/30 (NaN)		1/30 (3.3%)	1
Pregnancy, puerperium and perinatal conditions
Pregnancy, puerperium and perinatal conditions	/30 (NaN)		1/30 (3.3%)	1
Other (Not Including Serious) Adverse Events
	Arm I (CDX-301, CDX-1401, and Poly-ICLC)		Arm II (CDX-1401 and Poly-ICLC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/30 (100%)		30/30 (100%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders	13/30 (43.3%)	30	10/30 (33.3%)	17
Cardiac disorders
Cardiac disorders	1/30 (3.3%)	2	2/30 (6.7%)	2
Ear and labyrinth disorders
Ear and labyrinth disorders	3/30 (10%)	3	1/30 (3.3%)	1
Eye disorders
Eye disorders	4/30 (13.3%)	6	3/30 (10%)	5
Gastrointestinal disorders
Gastrointestinal disorders	15/30 (50%)	37	17/30 (56.7%)	44
General disorders
General disorders and administration site conditions	30/30 (100%)	509	30/30 (100%)	322
Immune system disorders
Immune system disorders	0/30 (0%)	0	1/30 (3.3%)	1
Infections and infestations
Infections and infestations	7/30 (23.3%)	10	9/30 (30%)	12
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications	10/30 (33.3%)	10	1/30 (3.3%)	1
Investigations
Investigations	14/30 (46.7%)	43	14/30 (46.7%)	49
Metabolism and nutrition disorders
Metabolism and nutrition disorders	15/30 (50%)	51	12/30 (40%)	28
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders	20/30 (66.7%)	56	18/30 (60%)	33
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)	3/30 (10%)	3	3/30 (10%)	3
Nervous system disorders
Nervous system disorders	17/30 (56.7%)	35	19/30 (63.3%)	49
Pregnancy, puerperium and perinatal conditions
Pregnancy, puerperium and perinatal conditions	0/30 (0%)	0	1/30 (3.3%)	1
Psychiatric disorders
Psychiatric disorders	6/30 (20%)	8	4/30 (13.3%)	4
Renal and urinary disorders
Renal and urinary disorders	2/30 (6.7%)	2	3/30 (10%)	4
Reproductive system and breast disorders
Reproductive system and breast disorders	1/30 (3.3%)	1	2/30 (6.7%)	2
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders	13/30 (43.3%)	27	13/30 (43.3%)	24
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders	15/30 (50%)	21	14/30 (46.7%)	24
Surgical and medical procedures
Surgical and medical procedures	2/30 (6.7%)	2	2/30 (6.7%)	2
Vascular disorders
Vascular disorders	8/30 (26.7%)	20	6/30 (20%)	26

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.