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A Study of Glembatumumab Vedotin as Monotherapy or in Combination With Immunotherapies in Patients With Advanced Melanoma

Sponsor
Celldex Therapeutics (Industry)
Overall Status
Terminated
CT.gov ID
NCT02302339
Collaborator
(none)
132
Enrollment
14
Locations
4
Arms
47
Duration (Months)
9.4
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will examine the effectiveness and safety of glembatumumab vedotin as monotherapy or in combination with immunotherapies in patients with advanced melanoma.

Condition or Disease Intervention/Treatment Phase
  • Drug: glembatumumab vedotin
  • Drug: glembatumumab vedotin and varlilumab
  • Drug: glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab)
  • Drug: glembatumumab vedotin and CDX-301
 Phase 2

Detailed Description

Glembatumumab vedotin consists of an antibody attached to a drug, monomethyl auristatin E (MMAE), that can kill cancer cells. The fully human antibody is designed to deliver the drug to cancer cells by attaching to a protein called glycoprotein NMB (gpNMB) that is expressed on the cancer cell. The MMAE is then released inside of the cell, where it interferes with cell growth and can lead to cell death of the targeted cell, as well as neighboring cells. Varlilumab is a fully human antibody that binds to CD27. This antibody allows the body's immune system to work against cancer cells. Nivolumab is a fully human antibody and pembrolizumab is a humanized antibody. Both bind to PD-1. CDX-301 is a fully human protein that helps boost production of certain white blood cells. This protein allows the body's immune system to work against tumor cells.

Eligible patients who enroll in the study will receive treatment with one of the following:

glembatumumab vedotin, glembatumumab vedotin and varlilumab, glembatumumab vedotin and CDX-301 or glembatumumab vedotin and either nivolumab OR pembrolizumab.

All patients enrolled in the study will be closely monitored to determine if their cancer is responding to treatment and for any side effects that may occur.

Study Design

Study Type:
Interventional
Actual Enrollment :
132 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Study of Glembatumumab Vedotin, an Anti-gpNMB Antibody-drug Conjugate, as Monotherapy or in Combination With Immunotherapies in Patients With Advanced Melanoma
Study Start Date :
Nov 1, 2014
Actual Primary Completion Date :
Jun 14, 2018
Actual Study Completion Date :
Oct 3, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Glembatumumab vedotin

glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle.

Drug: glembatumumab vedotin
Other Names:
  • Cohort 1

    		•
    Experimental: Glembatumumab vedotin and varlilumab

    glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Varlilumab administered as an intravenous infusion on Day 1 of cycles 1, 2, 4, 6, 8 and 10.

    Drug: glembatumumab vedotin and varlilumab
    Other Names:
  • Cohort 2

    		•
    Experimental: Glembatumumab vedotin and PD-1 targeted checkpoint inhibitor

    glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Nivolumab OR pembrolizumab administered according to institutional standard of care.

    Drug: glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab)
    Other Names:
  • Cohort 3

    		•
    Experimental: Glembatumumab vedotin and CDX-301

    glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. CDX-301 is injected once a day for five days before cycles 1 and 2.

    Drug: glembatumumab vedotin and CDX-301
    Other Names:
  • Cohort 4

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Objective Response Rate (ORR) [Every 6 to 9 weeks following treatment initiation until disease progression.]

      ORR is defined as the percentage of patients who achieved best overall response of complete or partial response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST version 1.1), Complete Response (CR) = disappearance of all target lesions and non-target lesions, Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions with no progression in non-target lesions and no new lesions. ORR was the primary outcome for Cohorts 1-3 and a secondary outcome for Cohort 4.

    2. Adverse Events of the Combination of Glembatumumab Vedotin and CDX-301 (in Cohort 4). [Up to 18 months following the screening visit]

      The percentage of patients experiencing one or more adverse events.

    Secondary Outcome Measures

    1. Duration of Response (DOR) [From start date of partial or complete response (whichever is achieved first) to first date that recurrent of progressive disease is objectively documented, assessed up to 18 months.]

      DOR is the number of months from the time criteria are first met for either CR or PR, until the first date that PD is objectively documented per RECIST 1.1.

    2. Progression-free Survival (PFS) [Evaluated every 6 to 9 weeks following treatment initiation until progression.]

      PFS is defined as the time from randomization to the earlier of disease progression or death due to any cause. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or progression in a non-target lesion, or the appearance of new lesions.

    3. Overall Survival (OS) [During treatment and every 3 months from end of treatment through death or end of study]

      Overall Survival (OS) is defined as the number of months from randomization to the date of death due to any cause.

    4. Correlation of Activity to gpNMB Expression [Up to 18 months following the screening visit]

      To investigate if the anti-cancer activity of glembatumumab vedotin as monotherapy or in combination with immunotherapies in advanced melanoma is dependent upon the degree of gpNMB expression in tumor tissue.

    5. Adverse Events [Following at least one dose of study treatment through 28 days after last dose of glembatumumab vedotin, or 70 calendar days after last administration of varlilumab, CDX-301 or PD-1 targeted checkpoint inhibitor (whichever occurs latest)]

      The percentage of patients experiencing one or more AEs will be summarized by relationship to study drug and severity.

    Eligibility Criteria

    Criteria

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

    Among other criteria, patients must meet all of the following conditions to be eligible for the study:

    • Unresectable, histologically-confirmed advanced (Stage III or Stage IV) melanoma

    • Disease progression during or after the last anticancer therapy received. For Cohort 3, progression must have occurred during the PD-1 targeted CPI (checkpoint inhibitor) treatment and the investigator has deemed it appropriate to continue treatment with the PD-1 targeted CPI beyond confirmed disease progression

    • No more than one prior chemotherapy-containing regimen for advanced disease.

    • Prior treatments received must include at least one CPI inhibitor (e.g., anti-CTLA-4, PD-1-, PD-L1-targeted immunotherapy) and for patients with a BRAF mutation at least one BRAF- or MEK-targeted therapy, unless patients are not candidates for, or refused, these therapies. For cohort 3, prior treatment received must include a PD-1 targeted CPI administered during the most recent disease progression and for patients with BRAF mutation at least one BRAF- or MEK-targeted therapy when appropriate

    • The study site will submit paraffin-embedded tumor tissue obtained from the patient for gpNMB analysis. Patients may require a biopsy if recent tumor tissue is not available. Patients in cohort 2 and 3 must submit a recently obtained biopsy of the skin fold for gpNMB analysis. Patients in Cohort 4 will submit a tumor tissue sample while on study.

    • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1

    • Adequate bone marrow, liver and renal function.

    Exclusion Criteria:

    Among other criteria, patients who meet any of the following conditions are NOT eligible for the study:

    • Previously received glembatumumab vedotin (CR011-vcMMAE, CDX-011) or other MMAE-containing agents

    • Treatment with the following therapies before the planned start of study treatment:

    1. BRAF or MEK inhibitors within 2 weeks

    2. Monoclonal based therapies within 4 weeks except for the PD-1 targeted checkpoint inhibitor in cohort 3

    3. Immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) within 2 weeks

    4. Chemotherapy within 21 days or at least 5 half-lives (whichever is longer)

    5. Investigational therapy within 2 weeks (or at least 5 half-lives, whichever is longer)

    • Patients with ocular melanoma

    • Neuropathy that is moderate (Grade 2) or worse.

    • Cancer that has spread to the brain or spine will be discussed with the study sponsor and may exclude patients from the trial.

    • History of another cancer except:

    1. Patients with adequately treated and cured non-melanoma skin cancer or in situ cancer

    2. Patients with any other cancer from which the patient has been disease-free for ≥ 3 years

    • Significant cardiovascular disease

    • Previously received varlilumab or any other anti-CD27 mAb (Cohort 2 only)

    • Active systemic infection requiring treatment

    • Treatment with immunosuppressive medications within 4 weeks or corticosteroids within two weeks

    • Patients with interstitial lung disease (Cohort 3 only)

    • Patients with active diverticulitis (Cohort 3 only)

    • Any non-study vaccination within 4 weeks, or influenza vaccine within 2 weeks, prior to CDX-301 dosing (Cohort 4 only)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The Angeles Clinic and Research Institute Los Angeles California United States 90025
    2 Northern California Melanoma Center/St. Mary's Medical Center San Francisco California United States 94117
    3 Florida Cancer Specialists Fort Myers Florida United States 33916
    4 Mount Sinai Comprehensive Cancer Center Miami Beach Florida United States 33140
    5 Florida Cancer Specialists West Palm Beach Florida United States 33407
    6 Northside Hospital Cancer Institute Atlanta Georgia United States 30341
    7 University of Chicago Medicine Chicago Illinois United States 60637
    8 Dana Farber Cancer Institute Boston Massachusetts United States 02115
    9 Henry Ford Hospital Detroit Michigan United States 48202
    10 New York University School of Medicine New York New York United States 10016
    11 Duke University Medical Center Durham North Carolina United States 27710
    12 Tennessee Oncology Nashville Tennessee United States 37203
    13 Vanderbilt-Ingram Cancer Center Nashville Tennessee United States 37232
    14 Baylor Research Institute-Sammons Cancer Center Dallas Texas United States 75246

    Sponsors and Collaborators

    • Celldex Therapeutics

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Celldex Therapeutics
    ClinicalTrials.gov Identifier:
    NCT02302339
    Other Study ID Numbers:
    • CDX011-05
    First Posted:
    Nov 27, 2014
    Last Update Posted:
    Sep 6, 2019
    Last Verified:
    Aug 1, 2019
    Keywords provided by Celldex Therapeutics
    Advanced melanoma
    Unresectable melanoma
    Metastatic melanoma
    Targeted Treatment for melanoma
    GPNMB
    CDX-011
    Glembatumumab vedotin
    Antibody-drug-conjugate
    Skin neoplasm
    Varlilumab
    CDX-1127
    Additional relevant MeSH terms:
    Melanoma
    Pembrolizumab
    Nivolumab
    Glembatumumab vedotin
    Antibodies, Monoclonal

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Glembatumumab Vedotin Glembatumumab Vedotin and Varlilumab Glembatumumab Vedotin and PD-1 Targeted Checkpoint Inhibitor Glembatumumab Vedotin and CDX-301
    Arm/Group Description glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. glembatumumab vedotin glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Varlilumab administered as an intravenous infusion on Day 1 of cycles 1, 2, 4, 6, 8 and 10. glembatumumab vedotin and varlilumab glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Nivolumab OR pembrolizumab administered according to institutional standard of care. glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab) glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. CDX-301 is injected once a day for five days before cycles 1 and 2. glembatumumab vedotin and CDX-301
    Period Title: Overall Study
    STARTED 62 34 29 7
    COMPLETED 61 32 28 7
    NOT COMPLETED 1 2 1 0

    Baseline Characteristics

    Arm/Group Title Glembatumumab Vedotin Glembatumumab Vedotin and Varlilumab Glembatumumab Vedotin and PD-1 Targeted Checkpoint Inhibitor Glembatumumab Vedotin and CDX-301 Total
    Arm/Group Description glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. glembatumumab vedotin glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Varlilumab administered as an intravenous infusion on Day 1 of cycles 1, 2, 4, 6, 8 and 10. glembatumumab vedotin and varlilumab glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Nivolumab OR pembrolizumab administered according to institutional standard of care. glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab) glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. CDX-301 is injected once a day for five days before cycles 1 and 2. glembatumumab vedotin and CDX-301 Total of all reporting groups
    Overall Participants 62 34 29 7 132
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    26
    41.9%
    21
    61.8%
    11
    37.9%
    6
    85.7%
    64
    48.5%
    >=65 years
    36
    58.1%
    13
    38.2%
    18
    62.1%
    1
    14.3%
    68
    51.5%
    Sex: Female, Male (Count of Participants)
    Female
    28
    45.2%
    14
    41.2%
    11
    37.9%
    4
    57.1%
    57
    43.2%
    Male
    34
    54.8%
    20
    58.8%
    18
    62.1%
    3
    42.9%
    75
    56.8%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    5
    8.1%
    2
    5.9%
    2
    6.9%
    0
    0%
    9
    6.8%
    Not Hispanic or Latino
    57
    91.9%
    32
    94.1%
    27
    93.1%
    7
    100%
    123
    93.2%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (Count of Participants)
    White
    61
    98.4%
    32
    94.1%
    27
    93.1%
    6
    85.7%
    126
    95.5%
    Black or African American
    1
    1.6%
    0
    0%
    0
    0%
    1
    14.3%
    2
    1.5%
    Asian
    0
    0%
    1
    2.9%
    0
    0%
    0
    0%
    1
    0.8%
    Other
    0
    0%
    1
    2.9%
    2
    6.9%
    0
    0%
    3
    2.3%

    Outcome Measures

    1. Primary Outcome
    Title Objective Response Rate (ORR)
    Description ORR is defined as the percentage of patients who achieved best overall response of complete or partial response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST version 1.1), Complete Response (CR) = disappearance of all target lesions and non-target lesions, Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions with no progression in non-target lesions and no new lesions. ORR was the primary outcome for Cohorts 1-3 and a secondary outcome for Cohort 4.
    Time Frame Every 6 to 9 weeks following treatment initiation until disease progression.

    Outcome Measure Data

    Analysis Population Description
    Response evaluable (at least one dose and a post treatment disease assessment)
    Arm/Group Title Glembatumumab Vedotin Glembatumumab Vedotin and Varlilumab Glembatumumab Vedotin and PD-1 Targeted Checkpoint Inhibitor Glembatumumab Vedotin and CDX-301
    Arm/Group Description glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. glembatumumab vedotin glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Varlilumab administered as an intravenous infusion on Day 1 of cycles 1, 2, 4, 6, 8 and 10. glembatumumab vedotin and varlilumab glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Nivolumab OR pembrolizumab administered according to institutional standard of care. glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab) glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. CDX-301 is injected once a day for five days before cycles 1 and 2. glembatumumab vedotin and CDX-301
    Measure Participants 62 31 28 5
    Count of Participants [Participants]
    7
    11.3%
    1
    2.9%
    4
    13.8%
    0
    0%
    2. Primary Outcome
    Title Adverse Events of the Combination of Glembatumumab Vedotin and CDX-301 (in Cohort 4).
    Description The percentage of patients experiencing one or more adverse events.
    Time Frame Up to 18 months following the screening visit

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Glembatumumab Vedotin and CDX-301
    Arm/Group Description glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. CDX-301 is injected once a day for five days before cycles 1 and 2. glembatumumab vedotin and CDX-301
    Measure Participants 7
    Leukopenia
    1
    1.6%
    Abdominal pain
    1
    1.6%
    Constipation
    2
    3.2%
    Dyspepsia
    2
    3.2%
    Nausea
    1
    1.6%
    Stomatitis
    1
    1.6%
    Vomiting
    1
    1.6%
    Fatigue
    3
    4.8%
    Hepatic pain
    1
    1.6%
    Mucosal infection
    1
    1.6%
    Urinary tract infection
    1
    1.6%
    Alanine aminotransferase increased
    2
    3.2%
    Aspartate aminotransferase increased
    3
    4.8%
    Blood alkaline phosphatase increased
    1
    1.6%
    Neutrophil count decreased
    1
    1.6%
    Platelet count decreased
    1
    1.6%
    Weight decreased
    1
    1.6%
    Decreased appetite
    1
    1.6%
    Hyperglycemia
    1
    1.6%
    Hyperuricemia
    1
    1.6%
    Hypokalemia
    1
    1.6%
    Myalgia
    1
    1.6%
    Pain in extremity
    1
    1.6%
    Peripheral sensory neuropathy
    1
    1.6%
    Anxiety
    1
    1.6%
    Depression
    1
    1.6%
    Vaginal hemorrhage
    1
    1.6%
    Vulvovaginal pain
    1
    1.6%
    Epistaxis
    1
    1.6%
    Alopecia
    3
    4.8%
    Rash erythematous
    1
    1.6%
    Rash maculopapular
    3
    4.8%
    Skin discoloration
    1
    1.6%
    Hypertension
    1
    1.6%
    3. Secondary Outcome
    Title Duration of Response (DOR)
    Description DOR is the number of months from the time criteria are first met for either CR or PR, until the first date that PD is objectively documented per RECIST 1.1.
    Time Frame From start date of partial or complete response (whichever is achieved first) to first date that recurrent of progressive disease is objectively documented, assessed up to 18 months.

    Outcome Measure Data

    Analysis Population Description
    Number of patients analyzed are the number of patients who achieved an objective response per Cohort. The response was observed at the last measurement without further follow up due to study closure.
    Arm/Group Title Glembatumumab Vedotin Glembatumumab Vedotin and Varlilumab Glembatumumab Vedotin and PD-1 Targeted Checkpoint Inhibitor Glembatumumab Vedotin and CDX-301
    Arm/Group Description glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. glembatumumab vedotin glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Varlilumab administered as an intravenous infusion on Day 1 of cycles 1, 2, 4, 6, 8 and 10. glembatumumab vedotin and varlilumab glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Nivolumab OR pembrolizumab administered according to institutional standard of care. glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab) glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. CDX-301 is injected once a day for five days before cycles 1 and 2. glembatumumab vedotin and CDX-301
    Measure Participants 7 1 4 0
    Median (95% Confidence Interval) [months]
    6.0
    2.2
    6.2
    4. Secondary Outcome
    Title Progression-free Survival (PFS)
    Description PFS is defined as the time from randomization to the earlier of disease progression or death due to any cause. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or progression in a non-target lesion, or the appearance of new lesions.
    Time Frame Evaluated every 6 to 9 weeks following treatment initiation until progression.

    Outcome Measure Data

    Analysis Population Description
    Response evaluable (at least one dose and a post treatment disease assessment). The analysis was not completed for the glembatumumab + CDX-301 cohort because sufficient data were not collected to perform the analysis.
    Arm/Group Title Glembatumumab Vedotin Glembatumumab Vedotin and Varlilumab Glembatumumab Vedotin and PD-1 Targeted Checkpoint Inhibitor Glembatumumab Vedotin and CDX-301
    Arm/Group Description glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. glembatumumab vedotin glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Varlilumab administered as an intravenous infusion on Day 1 of cycles 1, 2, 4, 6, 8 and 10. glembatumumab vedotin and varlilumab glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Nivolumab OR pembrolizumab administered according to institutional standard of care. glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab) glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. CDX-301 is injected once a day for five days before cycles 1 and 2. glembatumumab vedotin and CDX-301
    Measure Participants 62 31 28 0
    Median (95% Confidence Interval) [months]
    4.4
    2.6
    4.1
    5. Secondary Outcome
    Title Overall Survival (OS)
    Description Overall Survival (OS) is defined as the number of months from randomization to the date of death due to any cause.
    Time Frame During treatment and every 3 months from end of treatment through death or end of study

    Outcome Measure Data

    Analysis Population Description
    Response evaluable (at least one dose and a post treatment disease assessment). The analysis was not completed for the glembatumumab + CDX-301 cohort or the glembatumumab vedotin and PD-1 targeted checkpoint inhibitor cohort because sufficient data were not collected to perform the analysis.
    Arm/Group Title Glembatumumab Vedotin Glembatumumab Vedotin and Varlilumab Glembatumumab Vedotin and PD-1 Targeted Checkpoint Inhibitor Glembatumumab Vedotin and CDX-301
    Arm/Group Description glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. glembatumumab vedotin glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Varlilumab administered as an intravenous infusion on Day 1 of cycles 1, 2, 4, 6, 8 and 10. glembatumumab vedotin and varlilumab glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Nivolumab OR pembrolizumab administered according to institutional standard of care. glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab) glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. CDX-301 is injected once a day for five days before cycles 1 and 2. glembatumumab vedotin and CDX-301
    Measure Participants 62 31 0 0
    Median (95% Confidence Interval) [months]
    8.8
    6.6
    6. Secondary Outcome
    Title Correlation of Activity to gpNMB Expression
    Description To investigate if the anti-cancer activity of glembatumumab vedotin as monotherapy or in combination with immunotherapies in advanced melanoma is dependent upon the degree of gpNMB expression in tumor tissue.
    Time Frame Up to 18 months following the screening visit

    Outcome Measure Data

    Analysis Population Description
    Analysis not completed. gpNMB expression in tumor tissue was not done.
    Arm/Group Title Glembatumumab Vedotin Glembatumumab Vedotin and Varlilumab Glembatumumab Vedotin and PD-1 Targeted Checkpoint Inhibitor Glembatumumab Vedotin and CDX-301
    Arm/Group Description glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. glembatumumab vedotin glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Varlilumab administered as an intravenous infusion on Day 1 of cycles 1, 2, 4, 6, 8 and 10. glembatumumab vedotin and varlilumab glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Nivolumab OR pembrolizumab administered according to institutional standard of care. glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab) glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. CDX-301 is injected once a day for five days before cycles 1 and 2. glembatumumab vedotin and CDX-301
    Measure Participants 0 0 0 0
    7. Secondary Outcome
    Title Adverse Events
    Description The percentage of patients experiencing one or more AEs will be summarized by relationship to study drug and severity.
    Time Frame Following at least one dose of study treatment through 28 days after last dose of glembatumumab vedotin, or 70 calendar days after last administration of varlilumab, CDX-301 or PD-1 targeted checkpoint inhibitor (whichever occurs latest)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Glembatumumab Vedotin Glembatumumab Vedotin and Varlilumab Glembatumumab Vedotin and PD-1 Targeted Checkpoint Inhibitor Glembatumumab Vedotin and CDX-301
    Arm/Group Description glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. glembatumumab vedotin glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Varlilumab administered as an intravenous infusion on Day 1 of cycles 1, 2, 4, 6, 8 and 10. glembatumumab vedotin and varlilumab glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Nivolumab OR pembrolizumab administered according to institutional standard of care. glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab) glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. CDX-301 is injected once a day for five days before cycles 1 and 2. glembatumumab vedotin and CDX-301
    Measure Participants 62 34 29 7
    Count of Participants [Participants]
    61
    98.4%
    34
    100%
    29
    100%
    7
    100%

    Adverse Events

    Time Frame Adverse Events were recorded from the time the patient has taken at least one dose of study treatment through (whichever occurs first) either: a) 28 - 70 calendar days after the last administration of study drug depending on the cohort; or b) initiation of alternate anticancer therapy.
    Adverse Event Reporting Description
    Arm/Group Title Glembatumumab Vedotin Glembatumumab Vedotin and Varlilumab Glembatumumab Vedotin and PD-1 Targeted Checkpoint Inhibitor Glembatumumab Vedotin and CDX-301
    Arm/Group Description glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. glembatumumab vedotin glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Varlilumab administered as an intravenous infusion on Day 1 of cycles 1, 2, 4, 6, 8 and 10. glembatumumab vedotin and varlilumab glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Nivolumab OR pembrolizumab administered according to institutional standard of care. glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab) glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. CDX-301 is injected once a day for five days before cycles 1 and 2. glembatumumab vedotin and CDX-301
    All Cause Mortality
    Glembatumumab Vedotin Glembatumumab Vedotin and Varlilumab Glembatumumab Vedotin and PD-1 Targeted Checkpoint Inhibitor Glembatumumab Vedotin and CDX-301
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 53/62 (85.5%) 26/34 (76.5%) 8/29 (27.6%) 1/7 (14.3%)
    Serious Adverse Events
    Glembatumumab Vedotin Glembatumumab Vedotin and Varlilumab Glembatumumab Vedotin and PD-1 Targeted Checkpoint Inhibitor Glembatumumab Vedotin and CDX-301
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 19/62 (30.6%) 14/34 (41.2%) 14/29 (48.3%) 2/7 (28.6%)
    Blood and lymphatic system disorders
    Anaemia 2/62 (3.2%) 1/34 (2.9%) 0/29 (0%) 0/7 (0%)
    Febrile Neutropenia 1/62 (1.6%) 0/34 (0%) 0/29 (0%) 0/7 (0%)
    Neutropenia 3/62 (4.8%) 0/34 (0%) 1/29 (3.4%) 0/7 (0%)
    Cardiac disorders
    Acute Coronary Syndrome 0/62 (0%) 0/34 (0%) 1/29 (3.4%) 0/7 (0%)
    Angina Pectoris 1/62 (1.6%) 0/34 (0%) 0/29 (0%) 0/7 (0%)
    Atrial Fibrillation 0/62 (0%) 0/34 (0%) 1/29 (3.4%) 0/7 (0%)
    Gastrointestinal disorders
    Abdominal Pain 2/62 (3.2%) 0/34 (0%) 0/29 (0%) 1/7 (14.3%)
    Constipation 0/62 (0%) 1/34 (2.9%) 1/29 (3.4%) 0/7 (0%)
    Diarrhoea 1/62 (1.6%) 0/34 (0%) 0/29 (0%) 0/7 (0%)
    Enteritis 1/62 (1.6%) 0/34 (0%) 0/29 (0%) 0/7 (0%)
    Gastointestinal Haemorrhage 0/62 (0%) 1/34 (2.9%) 0/29 (0%) 0/7 (0%)
    Nausea 1/62 (1.6%) 0/34 (0%) 0/29 (0%) 0/7 (0%)
    Proctitis 0/62 (0%) 0/34 (0%) 1/29 (3.4%) 0/7 (0%)
    Small Intestinal Obstruction 1/62 (1.6%) 1/34 (2.9%) 0/29 (0%) 0/7 (0%)
    General disorders
    Fatigue 0/62 (0%) 1/34 (2.9%) 0/29 (0%) 0/7 (0%)
    Infusion Site Extravasation 1/62 (1.6%) 0/34 (0%) 0/29 (0%) 0/7 (0%)
    Multiple Organ Dysfunction Syndrome 0/62 (0%) 0/34 (0%) 2/29 (6.9%) 0/7 (0%)
    Non-Cardiac Chest Pain 0/62 (0%) 0/34 (0%) 1/29 (3.4%) 0/7 (0%)
    Pain 1/62 (1.6%) 0/34 (0%) 0/29 (0%) 0/7 (0%)
    Pyrexia 1/62 (1.6%) 1/34 (2.9%) 0/29 (0%) 0/7 (0%)
    Hepatobiliary disorders
    Hepatic Failure 0/62 (0%) 0/34 (0%) 1/29 (3.4%) 0/7 (0%)
    Infections and infestations
    Appendicitis 0/62 (0%) 0/34 (0%) 1/29 (3.4%) 0/7 (0%)
    Atypical Pneumonia 0/62 (0%) 0/34 (0%) 1/29 (3.4%) 0/7 (0%)
    Cellulitis 1/62 (1.6%) 2/34 (5.9%) 0/29 (0%) 0/7 (0%)
    Herpes Zoster 0/62 (0%) 1/34 (2.9%) 0/29 (0%) 0/7 (0%)
    Pneumonia 1/62 (1.6%) 0/34 (0%) 1/29 (3.4%) 0/7 (0%)
    Sepsis 0/62 (0%) 1/34 (2.9%) 4/29 (13.8%) 0/7 (0%)
    Septic Shock 1/62 (1.6%) 2/34 (5.9%) 0/29 (0%) 0/7 (0%)
    Skin Infection 1/62 (1.6%) 0/34 (0%) 0/29 (0%) 0/7 (0%)
    Injury, poisoning and procedural complications
    Subdural Haematoma 1/62 (1.6%) 0/34 (0%) 0/29 (0%) 0/7 (0%)
    Investigations
    Neutrophil Count Decreased 1/62 (1.6%) 0/34 (0%) 0/29 (0%) 1/7 (14.3%)
    White Blood Cell Count Decreased 1/62 (1.6%) 0/34 (0%) 0/29 (0%) 0/7 (0%)
    Metabolism and nutrition disorders
    Dehydration 3/62 (4.8%) 0/34 (0%) 1/29 (3.4%) 0/7 (0%)
    Diabetic Ketoacidosis 0/62 (0%) 1/34 (2.9%) 0/29 (0%) 0/7 (0%)
    Hyponatraemia 3/62 (4.8%) 0/34 (0%) 1/29 (3.4%) 0/7 (0%)
    Tumour Lysis Syndrome 0/62 (0%) 0/34 (0%) 1/29 (3.4%) 0/7 (0%)
    Musculoskeletal and connective tissue disorders
    Back Pain 0/62 (0%) 1/34 (2.9%) 0/29 (0%) 0/7 (0%)
    Myalgia 0/62 (0%) 0/34 (0%) 0/29 (0%) 1/7 (14.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer Pain 0/62 (0%) 0/34 (0%) 1/29 (3.4%) 0/7 (0%)
    Malignant Pleural Effusion 0/62 (0%) 1/34 (2.9%) 0/29 (0%) 0/7 (0%)
    Tumour Haemorrhage 0/62 (0%) 1/34 (2.9%) 0/29 (0%) 0/7 (0%)
    Nervous system disorders
    Intensive Care Unit Acquired Weakness 0/62 (0%) 1/34 (2.9%) 0/29 (0%) 0/7 (0%)
    Psychiatric disorders
    Confusional State 0/62 (0%) 1/34 (2.9%) 0/29 (0%) 0/7 (0%)
    Renal and urinary disorders
    Acute Kidney Injury 0/62 (0%) 0/34 (0%) 2/29 (6.9%) 0/7 (0%)
    Renal Failure 0/62 (0%) 1/34 (2.9%) 0/29 (0%) 0/7 (0%)
    Urinary Retention 1/62 (1.6%) 0/34 (0%) 0/29 (0%) 0/7 (0%)
    Reproductive system and breast disorders
    Vaginal Haemorrhage 0/62 (0%) 0/34 (0%) 0/29 (0%) 1/7 (14.3%)
    Respiratory, thoracic and mediastinal disorders
    Acute Respiratory Failure 0/62 (0%) 1/34 (2.9%) 1/29 (3.4%) 0/7 (0%)
    Dyspnoea 1/62 (1.6%) 0/34 (0%) 0/29 (0%) 0/7 (0%)
    Epistaxis 1/62 (1.6%) 0/34 (0%) 0/29 (0%) 0/7 (0%)
    Hypoxia 0/62 (0%) 0/34 (0%) 1/29 (3.4%) 0/7 (0%)
    Pleural Effusion 1/62 (1.6%) 0/34 (0%) 0/29 (0%) 0/7 (0%)
    Pleuritic Pain 0/62 (0%) 1/34 (2.9%) 0/29 (0%) 0/7 (0%)
    Pneumonitis 0/62 (0%) 0/34 (0%) 1/29 (3.4%) 0/7 (0%)
    Pneumothorax 1/62 (1.6%) 0/34 (0%) 0/29 (0%) 0/7 (0%)
    Respiratory Acidosis 0/62 (0%) 1/34 (2.9%) 0/29 (0%) 0/7 (0%)
    Respiratory Failure 0/62 (0%) 1/34 (2.9%) 0/29 (0%) 0/7 (0%)
    Skin and subcutaneous tissue disorders
    Rash Macular 1/62 (1.6%) 0/34 (0%) 0/29 (0%) 0/7 (0%)
    Rash Maculo-Papular 0/62 (0%) 1/34 (2.9%) 1/29 (3.4%) 0/7 (0%)
    Rash Pruritic 1/62 (1.6%) 0/34 (0%) 0/29 (0%) 0/7 (0%)
    Toxic Epidermal Necrolysis 0/62 (0%) 1/34 (2.9%) 0/29 (0%) 0/7 (0%)
    Vascular disorders
    Deep Vein Thrombosis 0/62 (0%) 1/34 (2.9%) 0/29 (0%) 0/7 (0%)
    Embolism 1/62 (1.6%) 0/34 (0%) 1/29 (3.4%) 0/7 (0%)
    Hypotension 0/62 (0%) 0/34 (0%) 1/29 (3.4%) 0/7 (0%)
    Other (Not Including Serious) Adverse Events
    Glembatumumab Vedotin Glembatumumab Vedotin and Varlilumab Glembatumumab Vedotin and PD-1 Targeted Checkpoint Inhibitor Glembatumumab Vedotin and CDX-301
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 61/62 (98.4%) 34/34 (100%) 29/29 (100%) 7/7 (100%)
    Blood and lymphatic system disorders
    Anemia 15/62 (24.2%) 13/34 (38.2%) 4/29 (13.8%) 0/7 (0%)
    Leukopenia 1/62 (1.6%) 1/34 (2.9%) 1/29 (3.4%) 1/7 (14.3%)
    Lymphopenia 0/62 (0%) 2/34 (5.9%) 0/29 (0%) 0/7 (0%)
    Neutropenia 7/62 (11.3%) 4/34 (11.8%) 7/29 (24.1%) 0/7 (0%)
    Cardiac disorders
    Atrial Fibrilation 0/62 (0%) 0/34 (0%) 2/29 (6.9%) 0/7 (0%)
    Palpitations 4/62 (6.5%) 0/34 (0%) 0/29 (0%) 0/7 (0%)
    Sinus Tachycardia 1/62 (1.6%) 2/34 (5.9%) 1/29 (3.4%) 0/7 (0%)
    Supraventricular Tachycardia 0/62 (0%) 0/34 (0%) 2/29 (6.9%) 0/7 (0%)
    Endocrine disorders
    Hypothyroidism 0/62 (0%) 0/34 (0%) 2/29 (6.9%) 0/7 (0%)
    Eye disorders
    Vision Blurred 3/62 (4.8%) 1/34 (2.9%) 2/29 (6.9%) 0/7 (0%)
    Gastrointestinal disorders
    Abdominal Distension 2/62 (3.2%) 0/34 (0%) 2/29 (6.9%) 0/7 (0%)
    Abdominal Pain 11/62 (17.7%) 6/34 (17.6%) 7/29 (24.1%) 1/7 (14.3%)
    Abdominal Pain Upper 3/62 (4.8%) 0/34 (0%) 2/29 (6.9%) 0/7 (0%)
    Constipation 14/62 (22.6%) 13/34 (38.2%) 11/29 (37.9%) 2/7 (28.6%)
    Diarrhoea 19/62 (30.6%) 15/34 (44.1%) 14/29 (48.3%) 0/7 (0%)
    Dry Mouth 6/62 (9.7%) 1/34 (2.9%) 3/29 (10.3%) 0/7 (0%)
    Dyspepsia 3/62 (4.8%) 3/34 (8.8%) 3/29 (10.3%) 2/7 (28.6%)
    Flatulence 1/62 (1.6%) 2/34 (5.9%) 2/29 (6.9%) 0/7 (0%)
    Gastrooesophageal Reflux Disease 4/62 (6.5%) 1/34 (2.9%) 2/29 (6.9%) 0/7 (0%)
    Haemorrhoids 1/62 (1.6%) 2/34 (5.9%) 0/29 (0%) 0/7 (0%)
    Ileus 1/62 (1.6%) 0/34 (0%) 2/29 (6.9%) 0/7 (0%)
    Nausea 23/62 (37.1%) 12/34 (35.3%) 16/29 (55.2%) 1/7 (14.3%)
    Oesophagitis 0/62 (0%) 0/34 (0%) 2/29 (6.9%) 0/7 (0%)
    Stomatits 7/62 (11.3%) 2/34 (5.9%) 6/29 (20.7%) 1/7 (14.3%)
    Vomiting 12/62 (19.4%) 10/34 (29.4%) 8/29 (27.6%) 1/7 (14.3%)
    General disorders
    Asthenia 4/62 (6.5%) 2/34 (5.9%) 2/29 (6.9%) 0/7 (0%)
    Chills 3/62 (4.8%) 2/34 (5.9%) 7/29 (24.1%) 0/7 (0%)
    Fatigue 26/62 (41.9%) 22/34 (64.7%) 11/29 (37.9%) 3/7 (42.9%)
    Influenza Like Illness 3/62 (4.8%) 2/34 (5.9%) 0/29 (0%) 0/7 (0%)
    Malaise 0/62 (0%) 0/34 (0%) 2/29 (6.9%) 0/7 (0%)
    Non-Cardiac Chest pain 2/62 (3.2%) 2/34 (5.9%) 2/29 (6.9%) 0/7 (0%)
    Oedema Peripheral 9/62 (14.5%) 3/34 (8.8%) 3/29 (10.3%) 0/7 (0%)
    Pain 4/62 (6.5%) 4/34 (11.8%) 1/29 (3.4%) 0/7 (0%)
    Pyrexia 6/62 (9.7%) 7/34 (20.6%) 6/29 (20.7%) 0/7 (0%)
    Hepatobiliary disorders
    Hepatic Pain 1/62 (1.6%) 1/34 (2.9%) 1/29 (3.4%) 1/7 (14.3%)
    Infections and infestations
    Candida Infection 2/62 (3.2%) 2/34 (5.9%) 4/29 (13.8%) 0/7 (0%)
    Eye Infection 0/62 (0%) 0/34 (0%) 2/29 (6.9%) 0/7 (0%)
    Mucosal Infection 0/62 (0%) 0/34 (0%) 1/29 (3.4%) 1/7 (14.3%)
    Oral Candidiasis 2/62 (3.2%) 6/34 (17.6%) 2/29 (6.9%) 0/7 (0%)
    Upper Respiratory Tract Infection 2/62 (3.2%) 2/34 (5.9%) 1/29 (3.4%) 0/7 (0%)
    Urinary Tract Infection 3/62 (4.8%) 2/34 (5.9%) 1/29 (3.4%) 1/7 (14.3%)
    Injury, poisoning and procedural complications
    Fall 1/62 (1.6%) 2/34 (5.9%) 1/29 (3.4%) 0/7 (0%)
    Procedural Site Reaction 0/62 (0%) 0/34 (0%) 2/29 (6.9%) 0/7 (0%)
    Wound 0/62 (0%) 2/34 (5.9%) 1/29 (3.4%) 0/7 (0%)
    Investigations
    Alanine Aminotransferase Increased 3/62 (4.8%) 5/34 (14.7%) 6/29 (20.7%) 2/7 (28.6%)
    Aspartate Aminotransferase Increased 8/62 (12.9%) 4/34 (11.8%) 7/29 (24.1%) 3/7 (42.9%)
    Blood Alkaline Phosphatase Increased 1/62 (1.6%) 2/34 (5.9%) 1/29 (3.4%) 1/7 (14.3%)
    Blood Creatinine Increased 5/62 (8.1%) 0/34 (0%) 1/29 (3.4%) 0/7 (0%)
    Lymphocyte Count Decreased 4/62 (6.5%) 1/34 (2.9%) 1/29 (3.4%) 0/7 (0%)
    Neutrophil Count Decreased 14/62 (22.6%) 5/34 (14.7%) 8/29 (27.6%) 1/7 (14.3%)
    Platelet Count Decreased 1/62 (1.6%) 0/34 (0%) 1/29 (3.4%) 1/7 (14.3%)
    Weight Decreased 10/62 (16.1%) 6/34 (17.6%) 7/29 (24.1%) 1/7 (14.3%)
    White Blood Cell Count Decreased 8/62 (12.9%) 4/34 (11.8%) 7/29 (24.1%) 0/7 (0%)
    Metabolism and nutrition disorders
    Cachexia 0/62 (0%) 2/34 (5.9%) 0/29 (0%) 0/7 (0%)
    Decreased Appetite 23/62 (37.1%) 13/34 (38.2%) 11/29 (37.9%) 1/7 (14.3%)
    Dehydration 9/62 (14.5%) 7/34 (20.6%) 6/29 (20.7%) 0/7 (0%)
    Hyperglaecemia 5/62 (8.1%) 4/34 (11.8%) 3/29 (10.3%) 1/7 (14.3%)
    Hyperkalaemia 5/62 (8.1%) 1/34 (2.9%) 1/29 (3.4%) 0/7 (0%)
    Hyperuricaemia 0/62 (0%) 0/34 (0%) 0/29 (0%) 1/7 (14.3%)
    Hypoalbuminaemia 7/62 (11.3%) 1/34 (2.9%) 1/29 (3.4%) 0/7 (0%)
    Hypocalcaemia 5/62 (8.1%) 1/34 (2.9%) 2/29 (6.9%) 0/7 (0%)
    Hypokalaemia 10/62 (16.1%) 3/34 (8.8%) 3/29 (10.3%) 1/7 (14.3%)
    Hypomagnesaemia 5/62 (8.1%) 1/34 (2.9%) 2/29 (6.9%) 0/7 (0%)
    Hyponatraemia 11/62 (17.7%) 5/34 (14.7%) 2/29 (6.9%) 0/7 (0%)
    Hypophosphataemia 3/62 (4.8%) 0/34 (0%) 3/29 (10.3%) 0/7 (0%)
    Malnutrition 1/62 (1.6%) 2/34 (5.9%) 1/29 (3.4%) 0/7 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 13/62 (21%) 4/34 (11.8%) 8/29 (27.6%) 0/7 (0%)
    Back Pain 9/62 (14.5%) 1/34 (2.9%) 3/29 (10.3%) 0/7 (0%)
    Flank Pain 0/62 (0%) 0/34 (0%) 2/29 (6.9%) 0/7 (0%)
    Muscle Spasma 2/62 (3.2%) 1/34 (2.9%) 2/29 (6.9%) 0/7 (0%)
    Muscular Weakness 8/62 (12.9%) 0/34 (0%) 3/29 (10.3%) 0/7 (0%)
    Musculoskeletal Chest Pain 3/62 (4.8%) 1/34 (2.9%) 2/29 (6.9%) 0/7 (0%)
    Muskuloskeletal Pain 4/62 (6.5%) 1/34 (2.9%) 1/29 (3.4%) 0/7 (0%)
    Myalgia 6/62 (9.7%) 3/34 (8.8%) 4/29 (13.8%) 1/7 (14.3%)
    Pain in Extremity 5/62 (8.1%) 2/34 (5.9%) 7/29 (24.1%) 1/7 (14.3%)
    Nervous system disorders
    Carpal Tunnel Syndrome 0/62 (0%) 2/34 (5.9%) 0/29 (0%) 0/7 (0%)
    Dizziness 6/62 (9.7%) 2/34 (5.9%) 3/29 (10.3%) 0/7 (0%)
    Dysgeusia 6/62 (9.7%) 2/34 (5.9%) 7/29 (24.1%) 0/7 (0%)
    Encephalopathy 0/62 (0%) 2/34 (5.9%) 2/29 (6.9%) 0/7 (0%)
    Headache 9/62 (14.5%) 5/34 (14.7%) 5/29 (17.2%) 0/7 (0%)
    Paraesthesia 4/62 (6.5%) 1/34 (2.9%) 2/29 (6.9%) 0/7 (0%)
    Peripheral Sensory Neuropathy 27/62 (43.5%) 8/34 (23.5%) 10/29 (34.5%) 1/7 (14.3%)
    Seizure 0/62 (0%) 2/34 (5.9%) 1/29 (3.4%) 0/7 (0%)
    Psychiatric disorders
    Anxiety 2/62 (3.2%) 2/34 (5.9%) 5/29 (17.2%) 1/7 (14.3%)
    Confusional State 1/62 (1.6%) 4/34 (11.8%) 1/29 (3.4%) 0/7 (0%)
    Depression 3/62 (4.8%) 0/34 (0%) 0/29 (0%) 1/7 (14.3%)
    Insomnia 11/62 (17.7%) 3/34 (8.8%) 7/29 (24.1%) 0/7 (0%)
    Restlessness 0/62 (0%) 0/34 (0%) 2/29 (6.9%) 0/7 (0%)
    Renal and urinary disorders
    Acute Kidney Injury 3/62 (4.8%) 3/34 (8.8%) 1/29 (3.4%) 0/7 (0%)
    Micronutrition Urgency 0/62 (0%) 0/34 (0%) 2/29 (6.9%) 0/7 (0%)
    Urinary Retention 1/62 (1.6%) 2/34 (5.9%) 0/29 (0%) 0/7 (0%)
    Reproductive system and breast disorders
    Vaginal Hemorrhage 0/62 (0%) 0/34 (0%) 0/29 (0%) 1/7 (14.3%)
    Vuvlovaginal Pain 0/62 (0%) 0/34 (0%) 0/29 (0%) 1/7 (14.3%)
    Respiratory, thoracic and mediastinal disorders
    Cough 5/62 (8.1%) 4/34 (11.8%) 3/29 (10.3%) 0/7 (0%)
    Dysphonia 5/62 (8.1%) 0/34 (0%) 3/29 (10.3%) 0/7 (0%)
    Dyspnoea 7/62 (11.3%) 5/34 (14.7%) 5/29 (17.2%) 0/7 (0%)
    Epistaxis 3/62 (4.8%) 1/34 (2.9%) 3/29 (10.3%) 1/7 (14.3%)
    Nasal Congestion 3/62 (4.8%) 1/34 (2.9%) 3/29 (10.3%) 0/7 (0%)
    Oropharyngeal Pain 2/62 (3.2%) 2/34 (5.9%) 5/29 (17.2%) 0/7 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia 30/62 (48.4%) 15/34 (44.1%) 15/29 (51.7%) 3/7 (42.9%)
    Decubitus Ulcer 0/62 (0%) 2/34 (5.9%) 0/29 (0%) 0/7 (0%)
    Dry Skin 1/62 (1.6%) 2/34 (5.9%) 1/29 (3.4%) 0/7 (0%)
    Erythema 5/62 (8.1%) 2/34 (5.9%) 1/29 (3.4%) 0/7 (0%)
    Night Sweats 0/62 (0%) 1/34 (2.9%) 2/29 (6.9%) 0/7 (0%)
    Pruritus 15/62 (24.2%) 10/34 (29.4%) 13/29 (44.8%) 0/7 (0%)
    Pruritis Generalised 2/62 (3.2%) 8/34 (23.5%) 3/29 (10.3%) 0/7 (0%)
    Rash 9/62 (14.5%) 4/34 (11.8%) 4/29 (13.8%) 0/7 (0%)
    Rash Erythaemous 2/62 (3.2%) 0/34 (0%) 2/29 (6.9%) 1/7 (14.3%)
    Rash Generalised 6/62 (9.7%) 3/34 (8.8%) 6/29 (20.7%) 0/7 (0%)
    Rash Mascular 4/62 (6.5%) 1/34 (2.9%) 0/29 (0%) 0/7 (0%)
    Rash Maculo-Papular 11/62 (17.7%) 13/34 (38.2%) 11/29 (37.9%) 3/7 (42.9%)
    Rash Pruritic 3/62 (4.8%) 2/34 (5.9%) 1/29 (3.4%) 0/7 (0%)
    Skin Discolouration 0/62 (0%) 0/34 (0%) 0/29 (0%) 1/7 (14.3%)
    Skin Hyperpigmentation 2/62 (3.2%) 2/34 (5.9%) 0/29 (0%) 0/7 (0%)
    Vitiligo 3/62 (4.8%) 0/34 (0%) 2/29 (6.9%) 0/7 (0%)
    Vascular disorders
    Hypertension 2/62 (3.2%) 1/34 (2.9%) 0/29 (0%) 1/7 (14.3%)
    Hypotension 7/62 (11.3%) 1/34 (2.9%) 2/29 (6.9%) 0/7 (0%)

    Limitations/Caveats

    Study was discontinued early, leading to small number of subjects analyzed in Cohort 4 and minimal patient follow up in Cohorts 3 and 4.

    More Information

    Certain Agreements

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

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Head of Regulatory Affairs
    Organization Celldex Therapeutics
    Phone 844-723-9363
    Email info@celldex.com
    Responsible Party:
    Celldex Therapeutics
    ClinicalTrials.gov Identifier:
    NCT02302339
    Other Study ID Numbers:
    • CDX011-05
    First Posted:
    Nov 27, 2014
    Last Update Posted:
    Sep 6, 2019
    Last Verified:
    Aug 1, 2019