Clinical Trials /

Study of DS-8273a With Nivolumab in Unresectable Stage III or Stage IV Melanoma

NCT02983006

Description:

The purpose of this study is to evaluate the safety profile, tolerability, and immunoregulatory (pharmacodynamic; PD) activity of DS-8273a administered in combination with nivolumab (anti-PD-1 antibody) to subjects with unresectable Stage III or Stage IV melanoma.

Related Conditions:
  • Melanoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of DS-8273a With Nivolumab in Unresectable Stage III or Stage IV Melanoma
  • Official Title: A Phase 1 Study of TRAIL-DR5 Antibody DS-8273a Administered in Combination With Nivolumab in Subjects With Unresectable Stage III or Stage IV Melanoma

Clinical Trial IDs

  • ORG STUDY ID: 15-00906
  • NCT ID: NCT02983006

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
DS-8273aDS-8273a & Nivolumab
NivolumabOpdivoDS-8273a & Nivolumab

Purpose

The purpose of this study is to evaluate the safety profile, tolerability, and immunoregulatory (pharmacodynamic; PD) activity of DS-8273a administered in combination with nivolumab (anti-PD-1 antibody) to subjects with unresectable Stage III or Stage IV melanoma.

Detailed Description

      Principal investigator hypothesize that TRAIL D5 antibody DS-8273a administered in
      combination with nivolumab will be well tolerated and that the addition of DS-8273a will
      augment the clinical efficacy of nivolumab.
    

Trial Arms

NameTypeDescriptionInterventions
DS-8273a & NivolumabExperimentalPatient groups (cohorts) will receive a single dose level of DS 8273a & Nivolumab; DS 8273a will be increased in subsequent cohorts.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  1) Signed Written Informed Consent The signed informed consent form prior to the
                 performance of any study related procedures that are not considered part of standard
                 of care.
    
                 2) Target Population
    
                   1. Subjects who are ipilimumab naïve with progressive unresectable Stage III or
                      Stage IV melanoma; eligible patients may have had prior adjuvant therapy, but
                      not including ipilimumab, and been treated with up to 3 prior treatments for
                      metastatic melanoma [eg, chemotherapy, other biologic or targeted therapy or
                      Interleukin-2 (IL-2)].
    
                   2. Histologic or cytologic confirmation of stage III or stage IV melanoma
    
                   3. Measurable disease at baseline as assessed by CT and/or MRI
    
                   4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
    
                   5. Screening laboratory values must meet the following criteria and should be
                      obtained within 7 days prior to registration • White blood cell (WBC) ≥ 2000/μL
                      • Neutrophils ≥ 1500/μL
    
                        -  Platelets ≥ 100 x103/μL
    
                        -  Hemoglobin > 9.0 g/dL
    
                        -  Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine
                           clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):
    
                        -  Female CrCl = (140 - age in years) x weight in kg x 0.85
    
                        -  72 x serum creatinine in mg/dL
    
                        -  Male CrCl = (140 - age in years) x weight in kg x 1.00
    
                        -  72 x serum creatinine in mg/dL
    
                        -  Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤ 3 x ULN
                           Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can
                           have total bilirubin < 3.0 mg/dL)
    
                           3) Age and Reproductive Status Men and women ≥ 18 years old
    
                   1. Men and women of childbearing potential (WOCBP) must be using an acceptable
                      method of contraception to avoid pregnancy throughout the study, and for women
                      at least 23 weeks after the last dose of investigational product and for men at
                      least 31 weeks after the last dose of investigational product in such a manner
                      that the risk of pregnancy is minimized. See Section 3.3.3 for the definition of
                      WOCBP.
    
                   2. Women must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or
                      equivalent units of HCG) within 24 hours prior to the start of investigational
                      product.
    
                      Exclusion Criteria:
    
              -  1) Target Disease Exceptions
    
                 a) Subjects with known or suspected brain metastasis, or brain as the only site of
                 disease are excluded with the following exceptions.
    
                 i) Subjects with controlled brain metastasis (no radiographic progression at least 4
                 weeks following radiation and/or surgical treatment, off steroids for at least 4
                 weeks, and have no new or progressing neurological signs or symptoms) will be
                 allowed.
    
                 b) Subjects with a history of prior malignancy with the exception of carcinoma in
                 situ of the cervix or other malignancy diagnosed > 2 years ago that has undergone
                 potentially curative therapy with no evidence of disease for the last ≥ 2 years and
                 that is deemed by the investigator to be at a low risk of recurrence.
    
                 2) Medical History and Concurrent Diseases
    
                 a) Active autoimmune disease or a history of known or suspected autoimmune disease
                 with the exception of subjects with isolated vitiligo, treated thyroiditis or
                 resolved childhood asthma/atopy.
    
                 b) Known human immunodeficiency virus (HIV), active hepatitis A, or hepatitis B or C
                 infection.
    
                 c) Evidence of active infection that requires anti-bacterial, anti-viral, or
                 anti-fungal therapy ≤ 7 days prior to initiation of study drug therapy d) History of
                 acute diverticulitis within the last 6 months, or current chronic diarrhea e) Active
                 peptic ulcer disease even if asymptomatic f) Prior organ allograft or allogenic bone
                 marrow transplantation g) Uncontrolled or significant cardiovascular disease
                 including, but not limited to, any of the following: i) Myocardial infarction within
                 the past 6 months ii) Uncontrolled angina within the past 6 months iii) Any history
                 of clinically significant ventricular arrhythmias (such as ventricular tachycardia,
                 ventricular fibrillation or Torsades de pointes). Controlled atrial fibrillation by
                 itself is not an exclusion criterion.
    
                 h) Baseline toxicities from prior anti-cancer treatments > Grade 1. i) Inability to
                 be venipunctured and/or tolerate venous access. j) Any major surgery within 4 weeks
                 or a diagnostic procedure (eg incision, needle biopsy) within 1 day of study drug
                 administration.
    
                 k) Known drug or alcohol abuse. l) Presence of underlying medical condition that in
                 the opinion of the Investigator or Sponsor could adversely affect the ability of the
                 subject to comply with or tolerate study procedures and/or study therapy, or confound
                 the ability to interpret the tolerability of combined administration of DS-8273A and
                 nivolumab in treated subjects.
    
                 3) Allergies and Adverse Drug Reaction
    
                 a) History of allergy to components of nivolumab or DS-8273A, or known allergy to
                 other antibody therapies.
    
                 4) Sex and Reproductive Status
    
                   1. WOCBP who are unwilling or unable to use an acceptable method to minimize the
                      risk of pregnancy for the entire study period and for at least 23 weeks after
                      the last dose of investigational product.
    
                   2. Women who are pregnant or breastfeeding.
    
                   3. Women with a positive pregnancy test on enrollment or prior to investigational
                      product administration.
    
                   4. Sexually active fertile men not using effective birth control if their partners
                      are WOCBP.
    
                      5) Prohibited Prior Treatments and/or Therapies
    
                 a) Exposure to any investigational drug within 4 weeks of study drug administration.
    
                 b) Any anti-cancer therapy (eg, chemotherapy, biologics, radiotherapy, or hormonal
                 treatment) within 4 weeks or at least 5 half-lives (whichever is longer) of study
                 drug administration.
    
                 c) Prior therapy with an anti-PD-1/PD-L1 antibody or a TRAIL-DR5 antibody d)
                 Concurrent chemotherapy, hormonal therapy, immunotherapy regimens, or radiation
                 therapy, standard or investigational.
    
                 6) Other Exclusion Criteria
    
                   1. Prisoners or subjects who are involuntarily incarcerated
    
                   2. Subjects who are compulsorily detained for treatment of either a psychiatric or
                      physical (eg, infectious disease) illness
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Safety (adverse events) of the protocol therapy
    Time Frame:Up to 2 years
    Safety Issue:
    Description:Safety will be evaluated for all treated subjects using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Secondary Outcome Measures

    Measure:Anti-tumor activity of the protocol therapy
    Time Frame:Up to 2 years
    Safety Issue:
    Description:Tumor response will be determined for all subjects by RECIST 1.1 as well as by immune-related response criteria

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:New York University School of Medicine

    Trial Keywords

    • TRAIL-DR5
    • DS-8273a
    • Immunoglobulin gamma-1 (IgG1)
    • Cell mediated cytotoxicity (ADCC)
    • Complement dependent cytotoxicity (CDC)
    • DR5
    • Immunoglobulin G4 (IgG4)
    • Monoclonal antibody
    • Programmed Cell Death 1 (PD-1)

    Last Updated

    December 2, 2016