Breast CancerPhase 1NCT03523572
Trastuzumab Deruxtecan With Nivolumab in Advanced Breast and Urothelial Cancer
A Phase 1 study testing Trastuzumab deruxtecan and Nivolumab in people with Breast Cancer and Urothelial Carcinoma, run by Daiichi Sankyo at 29 sites in 7 countries.
Trial summary
This is a study of trastuzumab deruxtecan 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Urothelial Carcinoma
- What is being tested?
- Trastuzumab deruxtecan and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 29 sitesin 7 countries
- Study dates
- 2 Aug 2018to 12 Sep 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Is the age of majority (adulthood) in their country
- Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1
- 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
- Has an adequate archival tumor sample available for the central laboratory to determine eligibility to participate
- Has at least 1 measurable lesion per RECIST version 1.1
- Has cardiac, bone marrow, kidney, liver, blood and clotting test results required per protocol
Show all 10Show fewer
- Has had an adequate washout period before enrollment since previous surgery and other treatment
- 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
- 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
- Has a life expectancy of at least 3 months
Who cannot join
- Has received prior treatment with nivolumab or trastuzumab deruxtecan
- 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.
- 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
- 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
- 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
- Is pregnant or breastfeeding, or planning to become pregnant
Trial locations and contacts
29 sites in 7 countries.
29 sites in 7 countries
United States10 sites
Gabrail Cancer Center Research
Canton, Ohio, 44718
Levine Cancer Institute Carolinas Healthcare System
Charlotte, North Carolina, 28204
Norton Cancer Institute
Louisville, Kentucky, 40202
University of Miami Hospital & Clinics/Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Tennessee Oncology - Sara Cannon Research Institute
Nashville, Tennessee, 37203
Yale University
New Haven, Connecticut, 06520
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
UCLA - Medical Center
Santa Monica, California, 90404
University of Washington Medical Center
Seattle, Washington, 98109
Spain5 sites
Hospital Gregorio Maranon Madrid Spain
Madrid, 28007
MD Anderson Cancer Center Madrid
Madrid, 28033
Hospital Universitario Ramon y Cajal Madrid
Madrid, 28034
Fundacion Jimenez Diaz
Madrid, 28040
START Madrid CIOCC
Madrid, 28050
Belgium3 sites
Cliniques Universitaires Saint-Luc
Brussels, 1200
AZ Groeninge
Kortrijk, West-Vlaanderen, 8500
GZA Hospital Campus Sint-Augustinus
Wilrijk, 2610
France3 sites
Institut de Cancerologie de L'Ouest
Angers, 49055
Centre Georges Francois Leclerc
Dijon, 21079
ICO Rene Gauducheau
Saint-Herblain, 44805
Germany3 sites
Charite Campus Benjamin Franklin
Berlin, Brandenburg, 12200
University Cancer Center
Dresden, Saxony, 01307
University Hospital Frankfurt
Frankfurt am Main, Hesse, 60590
Italy3 sites
Ospedale San Raffaele
Milan, 20132
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133
Azienda Ospedaliera Universitaria Senese U.O.C. Immunoterapia Oncologica
Siena, 53100
United Kingdom2 sites
Sarah Cannon Research Institute UK
London, England, W1G6AD
Royal Marsden Hospital (Surrey)
Sutton, SM25PT
About this study
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
This is a study of trastuzumab deruxtecan 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.
Read the 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 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
- Breast Cancer, Urothelial Carcinoma
- Being tested
- Trastuzumab deruxtecan, Nivolumab
- Keywords
- Human epidermal growth factor receptor-2, HER2, Refractory, Metastatic, Urothelial cancer, Breast Cancer
- Medical subject headings
- Breast Neoplasms, Carcinoma, Transitional Cell, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab deruxtecanDrug
Also called Enhertu®, T-DXd
The investigational product is a sterile lyophilized powder, which is made into solution for intravenous administration.
NivolumabDrug
Also called Opdivo®
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.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation (3.2 mg/kg) | Experimental | 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. Receives: Drug: Trastuzumab deruxtecan; Drug: Nivolumab |
| Dose Escalation (5.4 mg/kg) | Experimental | 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. Receives: Drug: Trastuzumab deruxtecan; Drug: Nivolumab |
| Dose Expansion - Cohort 1 | Experimental | 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. Receives: Drug: Trastuzumab deruxtecan; Drug: Nivolumab |
| Dose Expansion - Cohort 2 | Experimental | 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. Receives: Drug: Trastuzumab deruxtecan; Drug: Nivolumab |
| Dose Expansion - Cohort 3 | Experimental | 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. Receives: Drug: Trastuzumab deruxtecan; Drug: Nivolumab |
| Dose Expansion - Cohort 4 | Experimental | 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. Receives: Drug: Trastuzumab deruxtecan; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose-Limiting Toxicities at 3.2 mg/kg and 5.4 mg/kg Dose Level in Participants With HER2-expressing Advanced Breast Cancer in Dose Escalation
A Dose-Limiting Toxicity (DLT) is defined as any Treatment Emergent Adverse Event not attributable to disease or disease-related processes that occurs during the DLT evaluation period (2 complete cycles during Part 1) and is Grade 3 or above according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Each cycle is 21 days. Low dose was set at 3.2 mg/kg and high dose was set at 5.4 mg/kg.
Measured: Cycles 1 and 2 (each cycle is 21 days)
Percentage of Participants With Objective Response Rate (ORR) Based on Independent Central Review in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
The Objective Response Rate (ORR) was the defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by independent central review (ICR) committee based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR based on ICR is reported. As prespecified in the protocol, participants enrolled in Part 1 were pooled according to their trastuzumab deruxtecan dose and HER2 expressing levels (HER2 positive or HER2 low) for efficacy analyses. Participants who were dosed at 5.4 mg/kg of trastuzumab deruxtecan and have HER2-positive expression Breast Cancer (IHC score 3+ or IHC score 2+/ISH+) in Part 1 were pooled with the same participants from Part 2 (in this case, participants enrolled in Cohort 1).
Measured: Every 6 weeks in the first year after Day 1 of Cycle 1 and thereafter every 12 weeks until disease progression or initiation of additional anticancer therapy and survival, up to 2 years 11.5 months (each cycle is 21 days)
Secondary outcomes (7)
Duration of Response (DoR) in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
Duration of Response (DoR) was defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. DoR in participants with confirmed CR/PR based on independent central review and investigator assessment is reported. As prespecified in the protocol, participants enrolled in Part 1 were pooled according to their trastuzumab deruxtecan dose and HER2 expressing levels (HER2 positive or HER2 low) for efficacy analyses. Participants who were dosed at 5.4 mg/kg of trastuzumab deruxtecan and have HER2-positive expression Breast Cancer (IHC score 3+ or IHC score 2+/ISH+) in Part 1 were pooled with the same participants from Part 2 (in this case, participants enrolled in Cohort 1).
Measured: Every 6 weeks in the first year after Day 1 of Cycle 1 and thereafter every 12 weeks until disease progression or initiation of additional anticancer therapy and survival, up to 5 years (each cycle is 21 days)
Percentage of Participants With Disease Control Rate (DCR) in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
Disease Control Rate (DCR) was defined as the percentage of participants who achieved a best overall response of CR, PR, or stable disease (SD) during study treatment. CR was defined as a disappearance of all target lesions, PR as at least a 30% decrease in the sum of diameters of target lesions, and SD as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Confirmation of CR/PR was required. DCR based on independent central review and investigator assessment is reported. As prespecified in the protocol, participants enrolled in Part 1 were pooled according to their trastuzumab deruxtecan dose and HER2 expressing levels (HER2 positive or HER2 low) for efficacy analyses. Participants who were dosed at 5.4 mg/kg of trastuzumab deruxtecan and have HER2-positive expression Breast Cancer (IHC score 3+ or IHC score 2+/ISH+) in Part 1 were pooled with the same participants from Part 2 (in this case, participants enrolled in Cohort 1).
Measured: Every 6 weeks in the first year after Day 1 of Cycle 1 and thereafter every 12 weeks until disease progression or initiation of additional anticancer therapy and survival, up to 5 years (each cycle is 21 days)
Progression-Free Survival (PFS) in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
Progression-free survival (PFS) was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. PFS based on independent central review and investigator assessment is reported. As prespecified in the protocol, participants enrolled in Part 1 were pooled according to their trastuzumab deruxtecan dose and HER2 expressing levels (HER2 positive or HER2 low) for efficacy analyses. Participants who were dosed at 5.4 mg/kg of trastuzumab deruxtecan and have HER2-positive expression Breast Cancer (IHC score 3+ or IHC score 2+/ISH+) in Part 1 were pooled with the same participants from Part 2 (in this case, participants enrolled in Cohort 1).
Measured: Every 6 weeks in the first year after Day 1 of Cycle 1 and thereafter every 12 weeks until disease progression or initiation of additional anticancer therapy and survival, up to 5 years (each cycle is 21 days)
Time to Response (TTR) Based on Independent Central Review in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
Time to response (TTR) is defined as the time from the date of first dose of study treatment to the date of the first documented objective response (CR or PR). CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmation of CR/PR was required. TTR based on independent central review and investigator assessment is reported. As prespecified in the protocol, participants enrolled in Part 1 were pooled according to their trastuzumab deruxtecan dose and HER2 expressing levels (HER2 positive or HER2 low) for efficacy analyses. Participants who were dosed at 5.4 mg/kg of trastuzumab deruxtecan and have HER2-positive expression Breast Cancer (IHC score 3+ or IHC score 2+/ISH+) in Part 1 were pooled with the same participants from Part 2 (in this case, participants enrolled in Cohort 1).
Measured: Every 6 weeks in the first year after Day 1 of Cycle 1 and thereafter every 12 weeks until disease progression or initiation of additional anticancer therapy and survival, up to 5 years (each cycle is 21 days)
Overall Survival (OS) in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
Overall survival (OS) was defined as the time from the date of first dose of study drug to the date of death due to any cause. As prespecified in the protocol, participants enrolled in Part 1 were pooled according to their trastuzumab deruxtecan dose and HER2 expressing levels (HER2 positive or HER2 low) for efficacy analyses. Participants who were dosed at 5.4 mg/kg of trastuzumab deruxtecan and have HER2-positive expression Breast Cancer (IHC score 3+ or IHC score 2+/ISH+) in Part 1 were pooled with the same participants from Part 2 (in this case, participants enrolled in Cohort 1).
Measured: Date of first dose of study drug to the date of death due to any cause, up to 5 years
Percentage of Participants With Objective Response Rate (ORR) Based on Investigator Assessment in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
The Objective Response Rate (ORR) was the defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigator assessment (IA) based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR based on IA is reported. As prespecified in the protocol, participants enrolled in Part 1 were pooled according to their trastuzumab deruxtecan dose and HER2 expressing levels (HER2 positive or HER2 low) for efficacy analyses. Participants who were dosed at 5.4 mg/kg of trastuzumab deruxtecan and have HER2-positive expression Breast Cancer (IHC score 3+ or IHC score 2+/ISH+) in Part 1 were pooled with the same participants from Part 2 (in this case, participants enrolled in Cohort 1).
Measured: Every 6 weeks in the first year after Day 1 of Cycle 1 and thereafter every 12 weeks until disease progression or initiation of additional anticancer therapy and survival, up to 5 years (each cycle is 21 days)
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
A treatment-emergent adverse event (TEAE) was defined as an AE that occurred, having been absent before the first dose of study drug, or had worsened in severity or seriousness after initiating the study drug until 47 days after last dose of study drug.
Measured: Date of signing the informed consent form up to 100 days after last dose of study drug or start of a new anticancer drug (whichever occurs first), up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2018
- Study start2 Aug 2018
- Primary completion22 Jul 2021
- Study completion12 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Part 1 will be a sequential dose-finding (dose escalation) study, Part 2 will consist of a single group of four cohorts who receive the recommended dose (determined during Part 1)
- Masking
- None (open label)
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb, AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Global Team Leader, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03523572
- Sponsor's protocol ID
- DS8201-A-U105
- Other IDs
- 2018-000371-32, 2018
- Status last verified
- Dec 2024
- First submitted
- 30 Apr 2018
- Last updated
- 27 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03523572
- Acronym / sponsor ID
- DS8201-A-U105
- Conditions
- Breast Cancer, Urothelial Carcinoma
- Keywords
- Human epidermal growth factor receptor-2, HER2, Refractory, Metastatic, Urothelial cancer, Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb, AstraZeneca
- Study start
- 2 Aug 2018 (actual)
- Primary completion
- 22 Jul 2021 (actual)
- Study completion
- 12 Sep 2023 (actual)
- First posted
- 14 May 2018 (actual)
- Results
- Posted 27 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a study of trastuzumab deruxtecan 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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
- Model description
- Part 1 will be a sequential dose-finding (dose escalation) study, Part 2 will consist of a single group of four cohorts who receive the recommended dose (determined during Part 1)
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation (3.2 mg/kg) | Experimental | Drug: Trastuzumab deruxtecan, Drug: NivolumabParticipants 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. |
| Dose Escalation (5.4 mg/kg) | Experimental | Drug: Trastuzumab deruxtecan, Drug: NivolumabParticipants 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. |
| Dose Expansion - Cohort 1 | Experimental | Drug: Trastuzumab deruxtecan, Drug: NivolumabCohort 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. |
| Dose Expansion - Cohort 2 | Experimental | Drug: Trastuzumab deruxtecan, Drug: NivolumabCohort 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. |
| Dose Expansion - Cohort 3 | Experimental | Drug: Trastuzumab deruxtecan, Drug: NivolumabCohort 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. |
| Dose Expansion - Cohort 4 | Experimental | Drug: Trastuzumab deruxtecan, Drug: NivolumabCohort 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Is the age of majority (adulthood) in their country
- Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1
- 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
- Has an adequate archival tumor sample available for the central laboratory to determine eligibility to participate
- Has at least 1 measurable lesion per RECIST version 1.1
Key exclusion criteria (6 listed)
- Has received prior treatment with nivolumab or trastuzumab deruxtecan
- 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.
- 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
- 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
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trastuzumab deruxtecanAlso: Enhertu®, T-DXdThe investigational product is a sterile lyophilized powder, which is made into solution for intravenous administration. | Drug | Dose Escalation (3.2 mg/kg), Dose Escalation (5.4 mg/kg), Dose Expansion - Cohort 1, Dose Expansion - Cohort 2, Dose Expansion - Cohort 3, Dose Expansion - Cohort 4 |
| NivolumabAlso: Opdivo®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. | Drug | Dose Escalation (3.2 mg/kg), Dose Escalation (5.4 mg/kg), Dose Expansion - Cohort 1, Dose Expansion - Cohort 2, Dose Expansion - Cohort 3, Dose Expansion - Cohort 4 |
Primary outcome
Number of Participants With Dose-Limiting Toxicities at 3.2 mg/kg and 5.4 mg/kg Dose Level in Participants With HER2-expressing Advanced Breast Cancer in Dose Escalation
Time frame: Cycles 1 and 2 (each cycle is 21 days)
A Dose-Limiting Toxicity (DLT) is defined as any Treatment Emergent Adverse Event not attributable to disease or disease-related processes that occurs during the DLT evaluation period (2 complete cycles during Part 1) and is Grade 3 or above according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Each cycle is 21 days. Low dose was set at 3.2 mg/kg and high dose was set at 5.4 mg/kg.
Percentage of Participants With Objective Response Rate (ORR) Based on Independent Central Review in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
Time frame: Every 6 weeks in the first year after Day 1 of Cycle 1 and thereafter every 12 weeks until disease progression or initiation of additional anticancer therapy and survival, up to 2 years 11.5 months (each cycle is 21 days)
The Objective Response Rate (ORR) was the defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by independent central review (ICR) committee based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR based on ICR is reported. As prespecified in the protocol, participants enrolled in Part 1 were pooled according to their trastuzumab deruxtecan dose and HER2 expressing levels (HER2 positive or HER2 low) for efficacy analyses. Participants who were dosed at 5.4 mg/kg of trastuzumab deruxtecan and have HER2-positive expression Breast Cancer (IHC score 3+ or IHC score 2+/ISH+) in Part 1 were pooled with the same participants from Part 2 (in this case, participants enrolled in Cohort 1).
7 secondary outcomes
Duration of Response (DoR) in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
Time frame: Every 6 weeks in the first year after Day 1 of Cycle 1 and thereafter every 12 weeks until disease progression or initiation of additional anticancer therapy and survival, up to 5 years (each cycle is 21 days)
Percentage of Participants With Disease Control Rate (DCR) in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
Time frame: Every 6 weeks in the first year after Day 1 of Cycle 1 and thereafter every 12 weeks until disease progression or initiation of additional anticancer therapy and survival, up to 5 years (each cycle is 21 days)
Progression-Free Survival (PFS) in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
Time frame: Every 6 weeks in the first year after Day 1 of Cycle 1 and thereafter every 12 weeks until disease progression or initiation of additional anticancer therapy and survival, up to 5 years (each cycle is 21 days)
Time to Response (TTR) Based on Independent Central Review in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
Time frame: Every 6 weeks in the first year after Day 1 of Cycle 1 and thereafter every 12 weeks until disease progression or initiation of additional anticancer therapy and survival, up to 5 years (each cycle is 21 days)
Overall Survival (OS) in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
Time frame: Date of first dose of study drug to the date of death due to any cause, up to 5 years
Percentage of Participants With Objective Response Rate (ORR) Based on Investigator Assessment in Participants With HER2-expressing Advanced Breast Cancer or Urothelial Cancer
Time frame: Every 6 weeks in the first year after Day 1 of Cycle 1 and thereafter every 12 weeks until disease progression or initiation of additional anticancer therapy and survival, up to 5 years (each cycle is 21 days)
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: Date of signing the informed consent form up to 100 days after last dose of study drug or start of a new anticancer drug (whichever occurs first), up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Global Team Leader study director
Daiichi Sankyo
29 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Trastuzumab deruxtecan and Nivolumab in people with Breast Cancer and Urothelial Carcinoma, run by Daiichi Sankyo at 29 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Spain, Belgium, France, Germany and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose-Limiting Toxicities at 3.2 mg/kg and 5.4 mg/kg Dose Level in Participants With HER2-expressing Advanced Breast Cancer in Dose Escalation (time frame: Cycles 1 and 2 (each cycle is 21 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2025.