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

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.
• •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