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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

INTRODUCTION

  • Org Study ID: DS8201-A-U105
  • Secondary ID: 2018-000371-32
  • NTC ID: NCT03523572
  • Sponsor: Daiichi Sankyo, Inc.

BRIEF SUMMARY


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.

DETAILED DESCRIPTION


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
    Recruiting
  • Start Date
    June 20, 2018
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Part 1: Number of participants with dose-limiting toxicity at each dose level

Primary Outcome 1 - Timeframe: 2 cycles (within 2 months; each cycle is 21 days)

Primary Outcome 2 - Measure: Part 2: Dose expansion - Objective response rate (ORR) as assessed by Central Imaging Review

Primary Outcome 2 - Timeframe: 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)

CONDITION

  • Breast Cancer
  • Urothelial Carcinoma

ELIGIBILITY


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: N/A

Maximum Age: 18 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Global Team Leader

Role: Study Director

Affiliation: Daiichi Sankyo, Inc.

Overall Contact

Name: Global Team Leader

Phone: 908-992-6400

Email: CTRinfo@dsi.com

LOCATION

Facility Status Contact
Facility: UCLA - Medical Center
Santa Monica, California 90404-2125
United States
Status: Recruiting Contact:
Principal Investigator

Facility: Yale University
New Haven, Connecticut 06520
United States
Status: Recruiting Contact:
Principal Investigator

Facility: University of Miami Hospital & Clinics/Sylvester Comprehensive Cancer Center
Miami, Florida 33136
United States
Status: Recruiting Contact:
Principal Investigator

Facility: Norton Cancer Institute
Louisville, Kentucky 40202-3700
United States
Status: Recruiting Contact:
Principal Investigator

Facility: Icahn School of Medicine at Mount Sinai
New York, New York 10029-6504
United States
Status: Recruiting Contact:
Principal Investigator

Facility: Levine Cancer Institute Carolinas Healthcare System
Charlotte, North Carolina 28204
United States
Status: Recruiting Contact:
Principal Investigator

Facility: Tennessee Oncology - Sara Cannon Research Institute
Nashville, Tennessee 37203-1619
United States
Status: Recruiting Contact:
Principal Investigator

Facility: Huntsman Cancer Institute
Salt Lake City, Utah 84112
United States
Status: Recruiting Contact:
Principal Investigator

Facility: University of Washington Medical Center
Seattle, Washington 98109
United States
Status: Recruiting Contact:
Principal Investigator

Facility: AZ Groeninge
Kortrijk, West-Vlaanderen 8500
Belgium
Status: Recruiting Contact:
Principal Investigator

Facility: Cliniques Universitaires Saint-Luc
Brussels, 1200
Belgium
Status: Recruiting Contact:
Principal Investigator

Facility: GZA Hospital Campus Sint-Augustinus
Wilrijk, 2610
Belgium
Status: Recruiting Contact:
Principal Investigator

Facility: Centre Georges Francois Leclerc
Dijon, 21079
France
Status: Recruiting Contact:
Principal Investigator

Facility: ICO Rene Gauducheau
Saint-Herblain, 44805
France
Status: Recruiting Contact:
Principal Investigator

Facility: Charite Campus Benjamin Franklin
Berlin, Brandenburg 12200
Germany
Status: Recruiting Contact:
Principal Investigator

Facility: University Hospital Frankfurt
Frankfurt, Hessen 60590
Germany
Status: Recruiting Contact:
Principal Investigator

Facility: University Cancer Center
Dresden, Sachsen 01307
Germany
Status: Recruiting Contact:
Principal Investigator

Facility: Ospedale San Raffaele
Milano, 20132
Italy
Status: Recruiting Contact:
Principal Investigator

Facility: Fondazione IRCCS Istituto Nazionale dei Tumori
Milano, 20133
Italy
Status: Recruiting Contact:
Principal Investigator

Facility: Azienda Ospedaliera Universitaria Senese U.O.C. Immunoterapia Oncologica
Siena, 53100
Italy
Status: Recruiting Contact:
Principal Investigator

Facility: Hospital Gregorio Maranon Madrid Spain
Madrid, 28007
Spain
Status: Recruiting Contact:
Principal Investigator

Facility: MD Anderson Cancer Center Madrid
Madrid, 28033
Spain
Status: Recruiting Contact:
Principal Investigator

Facility: Hospital Universitario Ramon y Cajal Madrid
Madrid, 28034
Spain
Status: Recruiting Contact:
Principal Investigator

Facility: Fundacion Jimenez Diaz
Madrid, 28040
Spain
Status: Recruiting Contact:
Principal Investigator

Facility: START Madrid CIOCC
Madrid, 28050
Spain
Status: Recruiting Contact:
Principal Investigator

Facility: Sarah Cannon Research Institute UK
London, England W1G6AD
United Kingdom
Status: Recruiting Contact:
Principal Investigator

Facility: Royal Marsden Hospital (Surrey)
London Borough of Sutton, SM25PT
United Kingdom
Status: Recruiting Contact:
Principal Investigator