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BRIEF TITLE: Study of Trastuzumab Deruxtecan (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 Urothelial Cancer

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


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

Brief Summary

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.

Detailed Description


The purpose of this phase 1b (Phase 1/Phase 2) study is to assess the combination of a test
drug (DS-8201a) 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 DS-8201a 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.

Overal Status Start Date Phase Study Type
Recruiting June 20, 2018 Phase 1/Phase 2 Interventional

Primary Outcomes:

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

Primary Outcome 1 - Time Frame: 2 cycles (within 2 months)

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

Primary Outcome 2 - 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)

Primary Outcome 3 - Measure: Number of participants with treatment emergent adverse events (TEAEs) during the trial

Primary Outcome 3 - Time Frame: at the time of final database lock (anticipated within three years)

Condition:

  • Breast Cancer
  • Urothelial Carcinoma

Eligibility

Criteria:
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:

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

2. safety of study staff

3. analysis of results
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Global Team Leader

Role: Study Director

Affiliation: Daiichi Sankyo, Inc.

Locations

Facility Status Contact
UCLA - Medical Center
Santa Monica, California 90404-2125
United States
Recruiting Principal Investigator
310-829-5471
shurvitz@mednet.ucla.edu
Yale University
New Haven, Connecticut 06520
United States
Recruiting Principal Investigator
203-737-1600
daniel.petrylak@yale.edu
University of Miami Hospital & Clinics/Sylvester Comprehensive Cancer Center
Miami, Florida 33136
United States
Recruiting Principal Investigator
305-270-5302
fvalbini@med.miami.edu
Norton Cancer Institute
Louisville, Kentucky 40202-3700
United States
Recruiting Principal Investigator
502-561-8200
Arash.RezazadehKalebasty@nortonhealthcare.org
Icahn School of Medicine at Mount Sinai
New York, New York 10029-6504
United States
Recruiting Principal Investigator
212-241-3131
charles.shapiro@mssm.edu
Levine Cancer Institute Carolinas Healthcare System
Charlotte, North Carolina 28204
United States
Recruiting Principal Investigator
980-442-6035
Antoinette.tan@atriumhealth.org
Gabrail Cancer Center Research
Canton, Ohio 44718-2566
United States
Recruiting Principal Investigator
330-492-3345
NGABRAILMD@aol.com
Tennessee Oncology - Sara Cannon Research Institute
Nashville, Tennessee 37203-1619
United States
Recruiting Principal Investigator
615-329-7274
ehamilton@tnonc.com
Huntsman Cancer Institute
Salt Lake City, Utah 84112
United States
Recruiting Principal Investigator
801-585-0160
adam.cohen@hci.utah.edu
University of Washington Medical Center
Seattle, Washington 98109
United States
Recruiting Principal Investigator
206-606-6292
evanyu@u.washington.edu
Cliniques Universitaires Saint-Luc
Brussels, 1200
Belgium
Recruiting Principal Investigator
+32 027645457
jean.pascal.machiels@uclouvain.be
GZA Hospital Campus Sint-Augustinus
Wilrijk, 2610
Belgium
Recruiting Principal Investigator
+32 499551578
annemie.rutten.oncologie@gza.be
Ospedale San Raffaele
Milano, 20132
Italy
Recruiting Principal Investigator
+39 226434994
gianni.luca@hsr.it
Fondazione IRCCS Istituto Nazionale dei Tumori
Milano, 20133
Italy
Recruiting Principal Investigator
+39 223902402
andrea.necchi@istitutotumori.mi.it
Azienda Ospedaliera Universitaria Senese U.O.C. Immunoterapia Oncologica
Siena, 53100
Italy
Recruiting Principal Investigator
+39 577586303
mmaiocro@gmail.com
Hospital Gregorio Maranon Madrid Spain
Madrid, 28007
Spain
Recruiting Principal Investigator
+34 670580865
mmartin@geicam.org
MD Anderson Cancer Center Madrid
Madrid, 28033
Spain
Recruiting Principal Investigator
+34 917878600
egrande@mdanderson.es
Hospital Universitario Ramon y Cajal Madrid
Madrid, 28034
Spain
Recruiting Principal Investigator
+34 913368263
jacortes@vhio.net
Fundacion Jimenez Diaz
Madrid, 28040
Spain
Recruiting Principal Investigator
+34 915504800
victor.moreno@start.stoh.com
START Madrid CIOCC
Madrid, 28050
Spain
Recruiting Principal Investigator
+34 666209969
Valentina.Boni@start.stoh.com
Sarah Cannon Research Institute UK
London, England W1G6AD
United Kingdom
Recruiting Principal Investigator
+44 2032195251
tobias.arkenau@sarahcannonresearch.co.uk
Royal Marsden Hospital (Surrey)
London Borough of Sutton, SM25PT
United Kingdom
Recruiting Principal Investigator
+44 2086426011
Anna.Minchom@icr.ac.uk