Brief Title
Trastuzumab Deruxtecan With Nivolumab in Advanced Breast and Urothelial Cancer
Official Title
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
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Part 1: Number of participants with dose-limiting toxicity at each dose level
Secondary Outcome
Duration of Response (DoR)
Condition
Breast Cancer
Intervention
Trastuzumab deruxtecan
Study Arms / Comparison Groups
Dose Escalation
Description: Part 1 will enroll participants meeting the eligibility criteria set up for any of the 4 cohorts of Part 2 specified below using a 3 + 3 + 3 design. Escalating/de-escalating doses of trastuzumab deruxtecan in combination with a flat dose of nivolumab will be administered on Day 1 of each 21-day cycle. The recommended dose for expansion (RDE) will be calculated using data collected from this population in the first two cycles. These participants may continue to receive study treatment in subsequent cycles.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
99
Start Date
June 20, 2018
Completion Date
July 2022
Primary Completion Date
July 22, 2021
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 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
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Global Team Leader, ,
Location Countries
Belgium
Location Countries
Belgium
Administrative Informations
NCT ID
NCT03523572
Organization ID
DS8201-A-U105
Secondary IDs
2018-000371-32
Responsible Party
Sponsor
Study Sponsor
Daiichi Sankyo, Inc.
Collaborators
Bristol-Myers Squibb
Study Sponsor
Global Team Leader, Study Director, Daiichi Sankyo, Inc.
Verification Date
August 2021