Trial Outcomes & Findings for A Vaccine (CDX-1401) With or Without a Biologic Drug (CDX-301) for the Treatment of Patients With Stage IIB-IV Melanoma (NCT NCT02129075)

Last Updated: 2021-11-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

60 participants

Primary outcome timeframe

At 12 weeks after final vaccination

Results posted on

2021-11-16

Participant Flow

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

Participant milestones

Participant milestones
Measure	Arm I (CDX-301, CDX-1401, and Poly-ICLC) 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	Arm II (CDX-1401 and Poly-ICLC) 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
Overall Study STARTED	30	30
Overall Study COMPLETED	30	30
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (CDX-301, CDX-1401, and Poly-ICLC) n=30 Participants 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	Arm II (CDX-1401 and Poly-ICLC) n=30 Participants 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 n=60 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants	25 Participants n=7 Participants	47 Participants n=5 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Age, Continuous	54.6 years STANDARD_DEVIATION 13.4 • n=5 Participants	51.6 years STANDARD_DEVIATION 14.5 • n=7 Participants	53.1 years STANDARD_DEVIATION 13.9 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	21 Participants n=7 Participants	41 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	30 Participants n=5 Participants	28 Participants n=7 Participants	58 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants	28 Participants n=7 Participants	58 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: At 12 weeks after final vaccination

Outcome measures

Outcome measures
Measure	Arm I (CDX-301, CDX-1401, and Poly-ICLC) n=28 Participants 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	Arm II (CDX-1401 and Poly-ICLC) n=26 Participants 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
Immune T-cell Response to NY-ESO-1	15 Participants	10 Participants

SECONDARY outcome

Timeframe: Up to 12 weeks after final vaccination

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

Outcome measures

Outcome measures
Measure	Arm I (CDX-301, CDX-1401, and Poly-ICLC) n=30 Participants 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	Arm II (CDX-1401 and Poly-ICLC) n=28 Participants 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
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)	7 Participants	7 Participants

SECONDARY outcome

Timeframe: Up to 12 weeks after final vaccination

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Arm I (CDX-301, CDX-1401, and Poly-ICLC) n=15 Participants 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	Arm II (CDX-1401 and Poly-ICLC) n=16 Participants 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
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) cDCs	30.4 log 2 fold change Standard Deviation 16.98	0.9 log 2 fold change Standard Deviation 0.26
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) Monocytes	6.1 log 2 fold change Standard Deviation 2.11	1.0 log 2 fold change Standard Deviation 0.18
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) CD4 T cells	1.2 log 2 fold change Standard Deviation 0.28	1.1 log 2 fold change Standard Deviation 0.27
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) NK CD56br cells	5.8 log 2 fold change Standard Deviation 2.84	1.26 log 2 fold change Standard Deviation 0.32
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) CD8 T cells	1.3 log 2 fold change Standard Deviation 0.36	1.0 log 2 fold change Standard Deviation .26
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) pDC	16.5 log 2 fold change Standard Deviation 7.27	0.8 log 2 fold change Standard Deviation 0.24

SECONDARY outcome

Timeframe: Up to 600 days from first vaccine

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

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

Outcome measures

Outcome measures
Measure	Arm I (CDX-301, CDX-1401, and Poly-ICLC) n=12 Participants 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	Arm II (CDX-1401 and Poly-ICLC) n=9 Participants 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
Tumor Recurrence	360.3 days Standard Deviation 191.1	389.2 days Standard Deviation 223.2

SECONDARY outcome

Timeframe: Up to 1 year after patient's 12 week visit

Population: Data not collected

Overall survival not assessed

Outcome measures

Outcome data not reported

Adverse Events

Arm I (CDX-301, CDX-1401, and Poly-ICLC)

Serious events: 0 serious events

Other events: 30 other events

Deaths: 0 deaths

Arm II (CDX-1401 and Poly-ICLC)

Serious events: 4 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm I (CDX-301, CDX-1401, and Poly-ICLC) n=30 participants at risk 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	Arm II (CDX-1401 and Poly-ICLC) n=30 participants at risk 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
General disorders General disorders and administration site conditions	0.00% 0/30 Systematic evaluation by clinicaltrials.gov definition	3.3% 1/30 • Number of events 1 Systematic evaluation by clinicaltrials.gov definition
Infections and infestations Infections and infestations	0.00% 0/30 Systematic evaluation by clinicaltrials.gov definition	3.3% 1/30 • Number of events 1 Systematic evaluation by clinicaltrials.gov definition
Nervous system disorders Nervous system disorders	0.00% 0/30 Systematic evaluation by clinicaltrials.gov definition	3.3% 1/30 • Number of events 1 Systematic evaluation by clinicaltrials.gov definition
Pregnancy, puerperium and perinatal conditions Pregnancy, puerperium and perinatal conditions	0.00% 0/30 Systematic evaluation by clinicaltrials.gov definition	3.3% 1/30 • Number of events 1 Systematic evaluation by clinicaltrials.gov definition

Other adverse events

Additional Information

Dr. Martin A. Cheever

Fred Hutchinson Cancer Research Center

Phone: 206-667-4141

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm I (CDX-301, CDX-1401, and Poly-ICLC) n=30 participants at risk 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	Arm II (CDX-1401 and Poly-ICLC) n=30 participants at risk 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
General disorders General disorders and administration site conditions	100.0% 30/30 • Number of events 509 Systematic evaluation by clinicaltrials.gov definition	100.0% 30/30 • Number of events 322 Systematic evaluation by clinicaltrials.gov definition
Nervous system disorders Nervous system disorders	56.7% 17/30 • Number of events 35 Systematic evaluation by clinicaltrials.gov definition	63.3% 19/30 • Number of events 49 Systematic evaluation by clinicaltrials.gov definition
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	66.7% 20/30 • Number of events 56 Systematic evaluation by clinicaltrials.gov definition	60.0% 18/30 • Number of events 33 Systematic evaluation by clinicaltrials.gov definition
Gastrointestinal disorders Gastrointestinal disorders	50.0% 15/30 • Number of events 37 Systematic evaluation by clinicaltrials.gov definition	56.7% 17/30 • Number of events 44 Systematic evaluation by clinicaltrials.gov definition
Investigations Investigations	46.7% 14/30 • Number of events 43 Systematic evaluation by clinicaltrials.gov definition	46.7% 14/30 • Number of events 49 Systematic evaluation by clinicaltrials.gov definition
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	50.0% 15/30 • Number of events 21 Systematic evaluation by clinicaltrials.gov definition	46.7% 14/30 • Number of events 24 Systematic evaluation by clinicaltrials.gov definition
Metabolism and nutrition disorders Metabolism and nutrition disorders	50.0% 15/30 • Number of events 51 Systematic evaluation by clinicaltrials.gov definition	40.0% 12/30 • Number of events 28 Systematic evaluation by clinicaltrials.gov definition
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	43.3% 13/30 • Number of events 27 Systematic evaluation by clinicaltrials.gov definition	43.3% 13/30 • Number of events 24 Systematic evaluation by clinicaltrials.gov definition
Blood and lymphatic system disorders Blood and lymphatic system disorders	43.3% 13/30 • Number of events 30 Systematic evaluation by clinicaltrials.gov definition	33.3% 10/30 • Number of events 17 Systematic evaluation by clinicaltrials.gov definition
Infections and infestations Infections and infestations	23.3% 7/30 • Number of events 10 Systematic evaluation by clinicaltrials.gov definition	30.0% 9/30 • Number of events 12 Systematic evaluation by clinicaltrials.gov definition
Vascular disorders Vascular disorders	26.7% 8/30 • Number of events 20 Systematic evaluation by clinicaltrials.gov definition	20.0% 6/30 • Number of events 26 Systematic evaluation by clinicaltrials.gov definition
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	33.3% 10/30 • Number of events 10 Systematic evaluation by clinicaltrials.gov definition	3.3% 1/30 • Number of events 1 Systematic evaluation by clinicaltrials.gov definition
Psychiatric disorders Psychiatric disorders	20.0% 6/30 • Number of events 8 Systematic evaluation by clinicaltrials.gov definition	13.3% 4/30 • Number of events 4 Systematic evaluation by clinicaltrials.gov definition
Eye disorders Eye disorders	13.3% 4/30 • Number of events 6 Systematic evaluation by clinicaltrials.gov definition	10.0% 3/30 • Number of events 5 Systematic evaluation by clinicaltrials.gov definition
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps)	10.0% 3/30 • Number of events 3 Systematic evaluation by clinicaltrials.gov definition	10.0% 3/30 • Number of events 3 Systematic evaluation by clinicaltrials.gov definition
Renal and urinary disorders Renal and urinary disorders	6.7% 2/30 • Number of events 2 Systematic evaluation by clinicaltrials.gov definition	10.0% 3/30 • Number of events 4 Systematic evaluation by clinicaltrials.gov definition
Cardiac disorders Cardiac disorders	3.3% 1/30 • Number of events 2 Systematic evaluation by clinicaltrials.gov definition	6.7% 2/30 • Number of events 2 Systematic evaluation by clinicaltrials.gov definition
Ear and labyrinth disorders Ear and labyrinth disorders	10.0% 3/30 • Number of events 3 Systematic evaluation by clinicaltrials.gov definition	3.3% 1/30 • Number of events 1 Systematic evaluation by clinicaltrials.gov definition
Reproductive system and breast disorders Reproductive system and breast disorders	3.3% 1/30 • Number of events 1 Systematic evaluation by clinicaltrials.gov definition	6.7% 2/30 • Number of events 2 Systematic evaluation by clinicaltrials.gov definition
Surgical and medical procedures Surgical and medical procedures	6.7% 2/30 • Number of events 2 Systematic evaluation by clinicaltrials.gov definition	6.7% 2/30 • Number of events 2 Systematic evaluation by clinicaltrials.gov definition
Immune system disorders Immune system disorders	0.00% 0/30 Systematic evaluation by clinicaltrials.gov definition	3.3% 1/30 • Number of events 1 Systematic evaluation by clinicaltrials.gov definition
Pregnancy, puerperium and perinatal conditions Pregnancy, puerperium and perinatal conditions	0.00% 0/30 Systematic evaluation by clinicaltrials.gov definition	3.3% 1/30 • Number of events 1 Systematic evaluation by clinicaltrials.gov definition