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.
| Overal Status | Start Date | Phase | Study Type |
|---|---|---|---|
| Recruiting | June 20, 2018 | Phase 1 | Interventional |
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; 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 - 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)
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
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Gender: All
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Global Team Leader
Role: Study Director
Affiliation: Daiichi Sankyo, Inc.
Name: Daiichi Sankyo Contact for Clinical Trial Information
Phone: 908-992-6400
Email: CTRinfo@dsi.com
