Metastatic Breast CancerPhase 3DISCORDANTNCT06585969
A Randomised Trial Comparing Trastuzumab Deruxtecan to CDK4/6 Inhibitors in Non-luminal A, ER-positive/HER2-low Metastatic Breast Cancer
A Phase 3 study testing Trastuzumab deruxtecan (T-DXd), Ribociclib with ET and Abemaciclib with ET in people with Metastatic Breast Cancer and ER-positive Breast Cancer, run by Danish Breast Cancer Cooperative Group.
Trial summary
The objective of this trial, DBCG R25, will be to evaluate the effect of trastuzumab-deruxtecan versus standard of care on progression-free survival (PFS) in first-line for patients with non-Luminal A, ER-positive/HER2-negative metastatic breast cancer Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer, ER-positive Breast Cancer, Luminal B
- What is being tested?
- Trastuzumab deruxtecan (T-DXd), Ribociclib with ET and Abemaciclib with ET
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2026to 1 Jan 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women aged 18 or above.
- Radiologically/pathologically verified metastatic breast cancer.
- ER-positive (1% or more) and HER2-low (HER2 1+ or HER2 2+/ISH-neg)10,11.
- PAM50 Luminal B, HER2-enriched or Basal-like.
- Performance status 0-1.
- Evaluable disease
Who cannot join
- Patients who are incapable of understanding the written material received
- Patients with inaccessible tumour tissue
- Other malignant disease within 5 years (in situ cervix and non-melanoma skin cancer excluded)
About this study
The objective of this trial, DBCG R25, will be to evaluate the effect of trastuzumab-deruxtecan versus standard of care on progression-free survival (PFS) in first-line for patients with non-Luminal A, ER-positive/HER2-negative metastatic breast cancer
Read the detailed description
Study design and setting We will conduct an international, multicentre, open-label, randomised controlled trial. All oncological departments who treat patients with metastatic breast cancer can participate. The EU Clinical Trial Regulation will be applied.
Interventions Trial participants will be randomised to trastuzumab deruxtecan or standard treatment.
Trastuzumab deruxtecan
Patients randomised to trastuzumab deruxtecan will be treated as:
Trastuzumab deruxtecan until progression or intolerable toxicity, Trastuzumab deruxtecan: 5.4 mg/kg intravenous on day 1 of a 21 days cycle.
Standard
Patients randomised to standard will be treated as:
CDK4/6 inhibitor with an endocrine therapy until progression or intolerable toxicity CDK4/6 inhibitor: Physician's choice of ribociclib (600mg daily for 21 days in a 28 days cycle) or abemaciclib (150mg twice daily).
Endocrine therapy: letrozole (2.5mg daily), anastrozole (1mg daily), exemestane (25mg daily), tamoxifen (20mg daily) or fulvestrant (intramuscular 500mg every 4 weeks)
Other treatment Prophylactic antiemetics are allowed, including corticosteroids. Prophylactic antibiotics are allowed if deemed necessary for the patient. G-CSF is allowed when needed.
All other symptomatic treatment to perform best of care is allowed as long as name, administration and length is documented in the chart. Bone targeted agents are allowed. No other antineoplastic treatment is allowed.
Radiological evaluation Patients will initially be scanned every 9-12 weeks as per investigator's or co-investigator's discretion with minimum a CT of the thorax and abdomen or a FDG-PET/CT. Patients with response can have this interval extended. Upon progression treatment/control is to be done according to department preferences, but subsequent treatment and day of death must be registered.
- Being tested
- Trastuzumab deruxtecan (T-DXd), Ribociclib with ET, Abemaciclib with ET
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab deruxtecan (T-DXd)Drug
Also called Enhertu
Trastuzumab deruxtexan every three weeks
Ribociclib with ETDrug
Ribociclib with endocrine therapy
Abemaciclib with ETDrug
Abemaciclib with endocrine therapy
| Study group | Role | What they receive |
|---|---|---|
| Trastuzumab-deruxtecan | Experimental | Trastuzumab deruxtecan until progression or intolerable toxicity: 5.4 mg/kg intravenous on day 1 of a 21 days cycle. Receives: Drug: Trastuzumab deruxtecan (T-DXd) |
| Immunohistochemistry guided treatment (standard) | Active comparator | - CDK4/6 inhibitor with an endocrine therapy until progression og intolerable toxicity
* CDK4/6 inhibitor: Physician's choice of ribociclib (600mg daily for 21 days in a 4 week schedule) or abemaciclib (125mg twice daily).
* Endocrine therapy: letrozole (2.5mg daily), anastrozole (1mg daily), exemestane (25mg daily), tamoxifen (20mg daily) or fulvestrant (intramuscular 500mg every 4 weeks) Receives: Drug: Ribociclib with ET; Drug: Abemaciclib with ET |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary outcome
Progression-free survival (ITT)
Measured: Up to 4 years after inclusion
Secondary outcomes (5)
Overall survival
Overall survival in ITT cohort
Measured: Up to 4 years after inclusion
PFS by subtype
PFS by subtype (Luminal B, HER2-enriched and Basal-like)
Measured: Up to 4 years after inclusion
OS by subtype
OS by subtype (Luminal B, HER2-enriched and Basal-like)
Measured: Up to 4 years after inclusion
Quality of life
Quality of life EORTC QLQ-C30/BR23 during treatment and at progression.
Measured: During treatment, estimated 18-24 months
Toxicity
Toxicity on treatment (NCI-CTC v. 5.0)
Measured: During treatment, estimated 18-24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start1 Jan 2026
- Primary completion1 Jan 2026
- Study completion1 Jan 2026
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Danish Breast Cancer Cooperative Group
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tobias Berg, Danish Breast Cancer Cooperative Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06585969
- Sponsor's protocol ID
- DBCG-R25-DISCORDANT
- Acronym
- DISCORDANT
- Status last verified
- Oct 2024
- First submitted
- 23 Aug 2024
- Last updated
- 12 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Trial Comparing Trastuzumab Deruxtecan to CDK4/6 Inhibitors in Non-luminal A, ER-positive/HER2-low Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT06585969
- Acronym / sponsor ID
- DISCORDANT / DBCG-R25-DISCORDANT
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Danish Breast Cancer Cooperative GroupUniversity, hospital or other
- Study start
- 1 Jan 2026 (actual)
- Primary completion
- 1 Jan 2026 (actual)
- Study completion
- 1 Jan 2026 (actual)
- First posted
- 19 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this trial, DBCG R25, will be to evaluate the effect of trastuzumab-deruxtecan versus standard of care on progression-free survival (PFS) in first-line for patients with non-Luminal A, ER-positive/HER2-negative metastatic breast cancer
Detailed description
Study design and setting We will conduct an international, multicentre, open-label, randomised controlled trial. All oncological departments who treat patients with metastatic breast cancer can participate. The EU Clinical Trial Regulation will be applied.
Interventions Trial participants will be randomised to trastuzumab deruxtecan or standard treatment.
Trastuzumab deruxtecan
Patients randomised to trastuzumab deruxtecan will be treated as:
Trastuzumab deruxtecan until progression or intolerable toxicity, Trastuzumab deruxtecan: 5.4 mg/kg intravenous on day 1 of a 21 days cycle.
Standard
Patients randomised to standard will be treated as:
CDK4/6 inhibitor with an endocrine therapy until progression or intolerable toxicity CDK4/6 inhibitor: Physician's choice of ribociclib (600mg daily for 21 days in a 28 days cycle) or abemaciclib (150mg twice daily).
Endocrine therapy: letrozole (2.5mg daily), anastrozole (1mg daily), exemestane (25mg daily), tamoxifen (20mg daily) or fulvestrant (intramuscular 500mg every 4 weeks)
Other treatment Prophylactic antiemetics are allowed, including corticosteroids. Prophylactic antibiotics are allowed if deemed necessary for the patient. G-CSF is allowed when needed.
All other symptomatic treatment to perform best of care is allowed as long as name, administration and length is documented in the chart. Bone targeted agents are allowed. No other antineoplastic treatment is allowed.
Radiological evaluation Patients will initially be scanned every 9-12 weeks as per investigator's or co-investigator's discretion with minimum a CT of the thorax and abdomen or a FDG-PET/CT. Patients with response can have this interval extended. Upon progression treatment/control is to be done according to department preferences, but subsequent treatment and day of death must be registered.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Trastuzumab-deruxtecan | Experimental | Drug: Trastuzumab deruxtecan (T-DXd)Trastuzumab deruxtecan until progression or intolerable toxicity: 5.4 mg/kg intravenous on day 1 of a 21 days cycle. |
| Immunohistochemistry guided treatment (standard) | Active comparator | Drug: Ribociclib with ET, Drug: Abemaciclib with ET- CDK4/6 inhibitor with an endocrine therapy until progression og intolerable toxicity * CDK4/6 inhibitor: Physician's choice of ribociclib (600mg daily for 21 days in a 4 week schedule) or abemaciclib (125mg twice daily). * Endocrine therapy: letrozole (2.5mg daily), anastrozole (1mg daily), exemestane (25mg daily), tamoxifen (20mg daily) or fulvestrant (intramuscular 500mg every 4 weeks) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Women aged 18 or above.
- Radiologically/pathologically verified metastatic breast cancer.
- ER-positive (1% or more) and HER2-low (HER2 1+ or HER2 2+/ISH-neg)10,11.
- PAM50 Luminal B, HER2-enriched or Basal-like.
- Performance status 0-1.
Key exclusion criteria (3 listed)
- Patients who are incapable of understanding the written material received
- Patients with inaccessible tumour tissue
- Other malignant disease within 5 years (in situ cervix and non-melanoma skin cancer excluded)
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 deruxtecan (T-DXd)Also: EnhertuTrastuzumab deruxtexan every three weeks | Drug | Trastuzumab-deruxtecan |
| Ribociclib with ETRibociclib with endocrine therapy | Drug | Immunohistochemistry guided treatment (standard) |
| Abemaciclib with ETAbemaciclib with endocrine therapy | Drug | Immunohistochemistry guided treatment (standard) |
Primary outcome
Primary outcome
Time frame: Up to 4 years after inclusion
Progression-free survival (ITT)
5 secondary outcomes
Overall survival
Time frame: Up to 4 years after inclusion
PFS by subtype
Time frame: Up to 4 years after inclusion
OS by subtype
Time frame: Up to 4 years after inclusion
Quality of life
Time frame: During treatment, estimated 18-24 months
Toxicity
Time frame: During treatment, estimated 18-24 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2026.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Trastuzumab deruxtecan (T-DXd), Ribociclib with ET and Abemaciclib with ET in people with Metastatic Breast Cancer and ER-positive Breast Cancer, run by Danish Breast Cancer Cooperative Group.
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 6 inclusion and 3 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: withdrawn, as of the sponsor's last update on 12 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Primary outcome (time frame: Up to 4 years after inclusion). 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 12 Feb 2026.