A Phase 1b, Multicenter, Two-Part, Open-Label Study of DS-8201a, an Anti-Human Epidermal Growth Factor Receptor-2 (HER2)-Antibody Drug Conjugate (ADC), in Combination With Nivolumab, an Anti-PD-1 Antibody, for Subjects With HER2-expressing Advanced Breast and Urothelial Cancer

Condition: Breast Cancer, Urothelial Carcinoma


  • Drug: Trastuzumab deruxtecan (DS-8201a)
  • Drug: Nivolumab

Purpose: This is a study of DS-8201a, which is an experimental drug not approved yet by the FDA. Participants will receive this study drug along with a cancer drug that is already being used, called nivolumab. The study will be done in two parts: – Part 1 is to identify the recommended dose to use for treatment. – Part 2 is to find out how well the combination works, and how safe and tolerable it is.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03523572

Sponsor: Daiichi Sankyo, Inc.

Primary Outcome Measures:

  • Measure: Part 1: Number of participants with dose-limiting toxicity at each dose level
  • Time Frame: 2 cycles (within 2 months)
  • Safety Issue:
  • Measure: Part 2: Dose expansion – Objective response rate (ORR) as assessed by Central Imaging Review
  • Time Frame: 6 months after the last participant is enrolled, or when 80% of participants have experienced disease progression or discontinued study treatment, whichever occurs first (within 24 months)
  • Safety Issue:
  • Measure: Number of participants with treatment emergent adverse events (TEAEs) during the trial
  • Time Frame: at the time of final database lock (anticipated within three years)
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Duration of Response (DoR)
  • Time Frame: within 24 months
  • Safety Issue:
  • Measure: Disease Control Rate (DCR)
  • Time Frame: within 24 months
  • Safety Issue:
  • Measure: Progression Free Survival (PFS)
  • Time Frame: within 24 months
  • Safety Issue:
  • Measure: Time to Response based on central review
  • Time Frame: within 24 months
  • Safety Issue:
  • Measure: Overall Survival (OS)
  • Time Frame: within 24 months
  • Safety Issue:
  • Measure: ORR
  • Time Frame: within 24 months
  • Safety Issue:

Estimated Enrollment: 99

Study Start Date: June 20, 2018

Phase: Phase 1/Phase 2


  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  1. Is the age of majority (adulthood) in their country
  2. Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1
  3. Has pathologically documented breast cancer or urothelial cancer that is unresectable or metastatic, and refractory to or intolerant of existing therapy(ies) known to provide clinical benefit, and as specified in each study cohort
  4. Has an adequate archival tumor sample available for the central laboratory to determine eligibility to participate
  5. Has at least 1 measurable lesion per RECIST version 1.1
  6. Has cardiac, bone marrow, kidney, liver, blood and clotting test results required per protocol
  7. Has had an adequate washout period before enrollment since previous surgery and other treatment
  8. If reproduction is possible, agrees to use protocol-defined methods of contraception (or completely abstain from heterosexual intercourse) from screening to at least 5 months (females) or 7 months (males) after the last dose of study drug
  9. Agrees to avoid harvesting sperm or ova for any reason from screening to at least 5 months (females) or 7 months (males) after the last dose of study drug
  10. Has a life expectancy of at least 3 months
  11. If eligible for Part 2, is eligible for Part 1

Exclusion Criteria:

  1. Has received prior treatment with niovolumab or DS-8201a
  2. Has medical history of myocardial infarction within 6 months before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association classes II-IV), or tropinin levels consistent with myocardial infarction 28 days before enrollment
  3. Has a corrected QT interval by Fredericia (QTcF) prolongation to > 470 ms (females) or > 450 ms (males) based on an average of the screening triplicate 12-lead electrocardiogram
  4. Has history of non-infectious interstitial lung disease (ILD)/pneumonitis (that required steroids), has ILD/pneumonitis currently, or it cannot be ruled out by imaging at screening
  5. Has a condition (other than active autoimmune disease) that requires systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of starting study treatment
  6. Is pregnant or breastfeeding, or planning to become pregnant
  7. Is suspected to have certain other protocol-defined diseases based on past medical history, physical exam, blood tests, eye test and imaging at screening period
  8. Has received a live vaccine within 30 days before the first dose of study drug
  9. Is related to the investigator or another employee of the sponsor or the study site
  10. Is housed in an institution based on an order by the authorities or the court
  11. Is pregnant, breastfeeding, or planning to become pregnant
  12. Has participated in a therapeutic clinical study within 3 weeks before study drug treatment, or is currently participating in other investigational procedures
  13. Has or had any disease, psychiatric or medical condition, metastatic condition, drug/medication use or other condition that might, per protocol or in the opinion of the investigator, compromise:
  14. safety or well-being of the participant or offspring
  15. safety of study staff
  16. analysis of results


  • UCLA – Medical Center
  • Santa Monica California 90404-2125 United States
  • Yale University
  • New Haven Connecticut 06520 United States
  • University of Miami Hospital & Clinics/Sylvester Comprehensive Cancer Center
  • Miami Florida 33136 United States
  • Norton Cancer Institute
  • Louisville Kentucky 40202-3700 United States
  • Icahn School of Medicine at Mount Sinai
  • New York New York 10029-6504 United States
  • Levine Cancer Institute Carolinas Healthcare System
  • Charlotte North Carolina 28204 United States
  • Tennessee Oncology – Sara Cannon Research Institute
  • Nashville Tennessee 37203-1619 United States
  • Huntsman Cancer Institute
  • Salt Lake City Utah 84112 United States
  • University of Washington Medical Center
  • Seattle Washington 98109 United States
  • Ospedale San Raffaele
  • Milano 20132 Italy
  • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milano 20133 Italy
  • Azienda Ospedaliera Universitaria Senese U.O.C. Immunoterapia Oncologica
  • Siena 53100 Italy
  • Hospital Gregorio Maranon Madrid Spain
  • Madrid 28007 Spain
  • MD Anderson Cancer Center Madrid
  • Madrid 28033 Spain
  • Hospital Universitario Ramon y Cajal Madrid
  • Madrid 28034 Spain
  • Fundacion Jimenez Diaz
  • Madrid 28040 Spain
  • START Madrid CIOCC
  • Madrid 28050 Spain
  • Sarah Cannon Research Institute UK
  • London England W1G6AD United Kingdom
  • Royal Marsden Hospital (Surrey)
  • London Borough of Sutton SM25PT United Kingdom

View trial on ClinicalTrials.gov