Trastuzumab Deruxtecan With Nivolumab in Advanced Breast and Urothelial Cancer
NCT ID: NCT03523572
Last Updated: 2025-01-27
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1
86 participants
INTERVENTIONAL
2018-08-02
2023-09-12
Brief Summary
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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.
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Detailed Description
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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 maximum tolerated dose/recommended dose for expansion, when used in combination with nivolumab
* Part 2 is to assess the efficacy and safety of this dose combination.
Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Dose Escalation (3.2 mg/kg)
Participants with HER2-expressing breast cancer who received starting intravenous dose of trastuzumab deruxtecan at 3.2 mg/kg and a fixed intravenous dose of 360mg of nivolumab every 3 weeks (Q3W).
Escalating/de-escalating doses of trastuzumab deruxtecan in combination with a flat dose of nivolumab was administered on Day 1 of each 21-day cycle.
The DLT observation period will be the first 2 cycles.
Trastuzumab deruxtecan
The investigational product is a sterile lyophilized powder, which is made into solution for intravenous administration.
Nivolumab
Nivolumab is an aqueous solution formulated at 10 mg/mL to be administered at a flat dose of 360 mg IV over 30 minutes. Protocol-defined thyroid testing is required while taking nivolumab.
Dose Escalation (5.4 mg/kg)
Participants with HER2-expressing breast cancer who received starting intravenous dose of trastuzumab deruxtecan at 3.2 mg/kg and a fixed intravenous dose of 360mg of nivolumab every 3 weeks (Q3W).
Escalating/de-escalating doses of trastuzumab deruxtecan in combination with a flat dose of nivolumab was administered on Day 1 of each 21-day cycle.
The DLT observation period will be the first 2 cycles.
Trastuzumab deruxtecan
The investigational product is a sterile lyophilized powder, which is made into solution for intravenous administration.
Nivolumab
Nivolumab is an aqueous solution formulated at 10 mg/mL to be administered at a flat dose of 360 mg IV over 30 minutes. Protocol-defined thyroid testing is required while taking nivolumab.
Dose Expansion - Cohort 1
Cohort 1: Participants with pathologically documented advanced/metastatic breast cancer that has centrally-determined positive HER2 expression (IHC 3+ or IHC 2+/ISH+) \[as defined by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines\]. These participants received prior ado-trastuzumab emtansine (T-DM1).
Participants will receive the RDE of trastuzumab deruxtecan and the flat dose of nivolumab.
Trastuzumab deruxtecan
The investigational product is a sterile lyophilized powder, which is made into solution for intravenous administration.
Nivolumab
Nivolumab is an aqueous solution formulated at 10 mg/mL to be administered at a flat dose of 360 mg IV over 30 minutes. Protocol-defined thyroid testing is required while taking nivolumab.
Dose Expansion - Cohort 2
Cohort 2: Participants with pathologically documented advanced/metastatic breast cancer that has centrally-determined low HER2 expression (IHC 1+ or IHC 2+/ISH-), who have exhausted treatments that can confer any clinically meaningful benefit (eg, other therapies such as hormonal therapy for patients who are hormone receptor positive).
Participants received the RDE of trastuzumab deruxtecan and the flat dose of nivolumab.
Trastuzumab deruxtecan
The investigational product is a sterile lyophilized powder, which is made into solution for intravenous administration.
Nivolumab
Nivolumab is an aqueous solution formulated at 10 mg/mL to be administered at a flat dose of 360 mg IV over 30 minutes. Protocol-defined thyroid testing is required while taking nivolumab.
Dose Expansion - Cohort 3
Cohort 3: Participants with pathologically documented advanced/metastatic urothelial carcinoma that has centrally-determined HER2 expression of IHC 2+ or 3+, who received prior platinum-based therapy with documented progression.
Participants received the RDE of trastuzumab deruxtecan and the flat dose of nivolumab.
Trastuzumab deruxtecan
The investigational product is a sterile lyophilized powder, which is made into solution for intravenous administration.
Nivolumab
Nivolumab is an aqueous solution formulated at 10 mg/mL to be administered at a flat dose of 360 mg IV over 30 minutes. Protocol-defined thyroid testing is required while taking nivolumab.
Dose Expansion - Cohort 4
Cohort 4: Participants with pathologically documented advanced/metastatic urothelial carcinoma that has centrally-determined HER2 expression of IHC 1+, who received prior platinum-based therapy with documented progression.
Participants received the RDE of trastuzumab deruxtecan and the flat dose of nivolumab.
Trastuzumab deruxtecan
The investigational product is a sterile lyophilized powder, which is made into solution for intravenous administration.
Nivolumab
Nivolumab is an aqueous solution formulated at 10 mg/mL to be administered at a flat dose of 360 mg IV over 30 minutes. Protocol-defined thyroid testing is required while taking nivolumab.
Interventions
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Trastuzumab deruxtecan
The investigational product is a sterile lyophilized powder, which is made into solution for intravenous administration.
Nivolumab
Nivolumab is an aqueous solution formulated at 10 mg/mL to be administered at a flat dose of 360 mg IV over 30 minutes. Protocol-defined thyroid testing is required while taking nivolumab.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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
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
18 Years
ALL
No
Sponsors
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Bristol-Myers Squibb
INDUSTRY
AstraZeneca
INDUSTRY
Daiichi Sankyo
INDUSTRY
Responsible Party
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Principal Investigators
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Global Team Leader
Role: STUDY_DIRECTOR
Daiichi Sankyo
Locations
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UCLA - Medical Center
Santa Monica, California, United States
Yale University
New Haven, Connecticut, United States
University of Miami Hospital & Clinics/Sylvester Comprehensive Cancer Center
Miami, Florida, United States
Norton Cancer Institute
Louisville, Kentucky, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Levine Cancer Institute Carolinas Healthcare System
Charlotte, North Carolina, United States
Gabrail Cancer Center Research
Canton, Ohio, United States
Tennessee Oncology - Sara Cannon Research Institute
Nashville, Tennessee, United States
Huntsman Cancer Institute
Salt Lake City, Utah, United States
University of Washington Medical Center
Seattle, Washington, United States
AZ Groeninge
Kortrijk, West-Vlaanderen, Belgium
Cliniques Universitaires Saint-Luc
Brussels, , Belgium
GZA Hospital Campus Sint-Augustinus
Wilrijk, , Belgium
Institut de Cancerologie de L'Ouest
Angers, , France
Centre Georges Francois Leclerc
Dijon, , France
ICO Rene Gauducheau
Saint-Herblain, , France
Charite Campus Benjamin Franklin
Berlin, Brandenburg, Germany
University Hospital Frankfurt
Frankfurt am Main, Hesse, Germany
University Cancer Center
Dresden, Saxony, Germany
Ospedale San Raffaele
Milan, , Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, , Italy
Azienda Ospedaliera Universitaria Senese U.O.C. Immunoterapia Oncologica
Siena, , Italy
Hospital Gregorio Maranon Madrid Spain
Madrid, , Spain
MD Anderson Cancer Center Madrid
Madrid, , Spain
Hospital Universitario Ramon y Cajal Madrid
Madrid, , Spain
Fundacion Jimenez Diaz
Madrid, , Spain
START Madrid CIOCC
Madrid, , Spain
Sarah Cannon Research Institute UK
London, England, United Kingdom
Royal Marsden Hospital (Surrey)
Sutton, , United Kingdom
Countries
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Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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2018-000371-32
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
DS8201-A-U105
Identifier Type: -
Identifier Source: org_study_id
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