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Brief Title: Trastuzumab Deruxtecan With Nivolumab in Advanced Breast and Urothelial Cancer

A Phase 1b, Multicenter, Two-Part, Open-Label Study of Trastuzumab Deruxtecan, 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


  • Org Study ID: DS8201-A-U105
  • Secondary ID: N/A
  • NCT ID: NCT03523572
  • Sponsor: Daiichi Sankyo


This is a study of trastuzumab deruxtecan, which was approved by the FDA (in December 2019) for the treatment of HER2-positive unresectable or metastatic breast cancer following two or more prior anti-HER2 based regimens.

Participants will receive this study drug along with a cancer drug, an immune checkpoint inhibitor, anti-PD1, 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.


The purpose of this phase 1b (Part 1, Part 2) study is to assess the combination of a test drug (trastuzumab deruxtecan) with nivolumab in participants with HER2-expressing breast and urothelial cancer who had disease progression during or after prior therapies, did not respond to standard therapies, or for whom no standard therapy is available.

The study will be performed in 2 parts.

* Part 1 is to test different doses of trastuzumab deruxtecan when given along with a fixed dose of nivolumab, and establish the most effective and the maximum/recommended tolerated dose, when used in combination with nivolumab
* Part 2 is to assess the efficacy and safety of this dose combination.

  • Overall Status
    Unknown status
  • Start Date
    June 20, 2018
  • Phase
    Phase 1
  • Study Type


Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A


  • Breast Cancer
  • Urothelial Carcinoma


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 7 months for females and males after the last dose of study drug

- 9. Agrees to avoid harvesting sperm or ova for any reason from screening to at least 7 months for females and males after the last dose of study drug

- 10. Has a life expectancy of at least 3 months
Exclusion Criteria:
1. Has received prior treatment with nivolumab or trastuzumab deruxtecan

- 2. Has medical history of myocardial infarction (MI) within 6 months before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association classes II-IV). Troponin levels above upper limit of normal (ULN) at screening (as defined by the manufacturer) and without any MI-related symptoms should have a cardiologic consultation before enrollment to rule out MI.

- 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 pregnant, breastfeeding, or planning to become pregnant

- 11. 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:
1. safety or well-being of the participant or offspring

- 2. safety of study staff

- 3. analysis of results

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No


Name: Global Team Leader

Role: Study Director

Affiliation: Daiichi Sankyo

Overall Contact

Name: N/A

Phone: N/A

Email: N/A


Facility Status Contact