A Study of Dato-DXd in Inoperable or Metastatic Hormone Receptor-positive, HER2 IHC 0 Breast Cancer

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified April 2026 by AstraZeneca
Sponsor
AstraZeneca
Information Provided by (Responsible Party)
AstraZeneca
Clinicaltrials.gov Identifier
NCT07205822
Other Study ID Numbers:
D9260C00003
First Submitted
September 10, 2025
First Posted
October 2, 2025
Last Update Posted
May 11, 2026
Last Verified
April 2026

ClinicalTrials.gov processed this data on May 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

This is a Phase IIIb, single-arm, open-label, multicentre, multinational study assessing the efficacy and safety of Dato-DXd in participants with HR-positive, HER2 IHC 0, locally advanced inoperable or metastatic breast cancer refractory to endocrine therapy.

Refer to the study schema (Figure 1) and SoA (Section 1.3) for overall design and required assessments. Day 1 is defined as the first day of study treatment.

Approximately 100 participants will be treated in this study with Dato-DXd 6 mg/kg as an intravenous infusion every 3 weeks (21-day cycle), up to a maximum of 540 mg for patients ≥ 90kg. Participants will receive study intervention until RECIST 1.1 defined radiological progression by investigator unless there is evidence of unacceptable toxicity or if the participant requests to stop the study treatment.

Written consent is required from all participants for newly acquired tumour biopsy collection at baseline or for providing a tumour biopsy sample collected within 6 weeks prior to initiating Dato-DXd and, if feasible, at progression. This sample will be used to assess for HER2 and TROP2 expression and exploratory analysis of biomarkers of response. Participants are also expected to consent for repeated liquid biopsy at baseline, during the treatment period, and at progression to evaluate biomarkers of response and resistance. (Sample collection in China will comply with local regulatory requirements.) Tumour imaging will occur every 8 weeks (± 1 week) after the first dose of study drug for 48 weeks and then every 12 weeks (± 1 week) thereafter until RECIST 1.1 disease progression as assessed by the investigator or the start of subsequent anticancer therapy.

Condition or DiseaseIntervention/Treatment
Breast Cancer
Drug: Dato-DXd

Study Design

Study TypeInterventional
Actual Enrollment100 participants
Design AllocationN/A
Interventional ModelSingle Group Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleA Phase IIIb, Open-label, Multinational Study Assessing the Efficacy and Safety of Dato-DXd Treatment in Patients With HRpositive, HER2 IHC 0, Locally Advanced Inoperable or Metastatic Breast Cancer Refractory to Endocrine Therapy (TROPION-Breast06)
Study Start DateOctober 29, 2025
Actual Primary Completion Date1yr 7mos from now
Actual Study Completion Date1yr 7mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
single arm group
All participants will receive Dato-DXd (6 mg/kg IV on Day 1, Q3W; up to a maximum of 540 mg Q3W for participants ≥ 90 kg) until investigator-defined disease progression according to RECIST 1.1 or until unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met.
Drug: Dato-DXd
All participants will receive Dato-DXd (6 mg/kg IV on Day 1, Q3W; up to a maximum of 540 mg Q3W for participants ≥ 90 kg) until investigator-defined disease progression according to RECIST 1.1 or until unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met. Continued treatment with the same study drug post-progression may be allowed, based on prior discussion with sponsor/sponsor representative/study physician on a case-by-case basis following written investigator's confirmation of continuing clinical benefit to the patient post progression. The study is anticipated to enrol for an 18-month period, and DCO is expected to occur approximately 6 months after the last participant has been dosed.

Outcome Measures

Primary Outcome Measures
  1. Progression Free Survival (PFS) per RECIST 1.1 as assessed by the investigator
    PFS is defined as time from date of first dose of study intervention until progression per RECIST 1.1 as assessed by the investigator or death due to any cause.
Secondary Outcome Measures
  1. Proportion of participants with oral mucositis/stomatitis
    Proportion of participants with oral mucositis/stomatitis
  2. Proportion of participants with ocular events
    Proportion of participants with ocular events
  3. Proportion of participants with Grade 3 or higher Adverse Events (AEs) possibly related to Dato-DXd treatment
    Grade 3 or higher adverse events possibly related to Dato-DXd treatment (Grade ≥ 3 treatment-related adverse events) according to NCI CTCAE 5.0. Possibly related is defined as reasonable possibility that the adverse event was caused by investigational product, as assessed by investigator. Missing responses are counted as possibly related.
  4. Clinical benefit rate (CBR) at 24 weeks
    CBR at 24 weeks is defined as the percentage of participants who have a confirmed CR or PR or who have SD per RECIST 1.1 as assessed by the investigator and derived from the raw tumour data for at least 24 weeks after date of first dose.
  5. Objective response rate (ORR)
    ORR is defined as the proportion of participants with measurable disease at baseline who have a confirmed CR or confirmed PR, as assessed by the investigator and derived from raw tumour data per RECIST 1.1.
  6. Duration of response (DoR)
    DoR will be defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1 as assessed by the investigator or death due to any cause. The analysis will include all dosed participants who have a confirmed response.
  7. Overall survival (OS)
    OS defined as the time from the date of the first dose of study intervention until the date of death due to any cause. All deaths will be included, regardless of whether the participant withdraws from therapy or receives another anticancer therapy

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
1. Participant must be ≥ 18 years (and above legal age) at the time of screening. 2. Inoperable or metastatic HR-positive, HER2 IHC 0 breast cancer (per ASCO/CAP guidelines, on local laboratory results); ie, is documented as HR-positive (either ER and/or PgR positive \[ER or PgR ≥ 1%\]) and HER2 IHC 0 (defined as no staining or incomplete and faint/barely perceptible membrane staining in ≤ 10% of tumour cells). 3. Progressed on and not suitable for further endocrine therapy per investigator assessment. 4. ECOG performance status of 0 or 1, with no deterioration over the previous 2 weeks prior to the first dose of study intervention. 5. Minimum life expectancy of 12 weeks at screening. 6. Provision of acceptable tumour sample (no more than 6 weeks old) prior to the first dose of study intervention or retrospectively as defined in the Laboratory Manual and the Diagnostic Testing Manual 7. Participants must have measurable disease as per RECIST 1.1 or evaluable disease. Lesions that will be subject to mandatory biopsy before, during, and after the dosing cannot be considered as TLs as per RECIST requirements. 8. Adequate bone marrow reserve and organ function within 7 days before the first dose of study intervention. 1. Haemoglobin ≥ 9.0 g/dL (red blood cell/plasma transfusion is not allowed within 1 week prior to screening assessment). 2. Absolute neutrophil count ≥ 1.5×109/L (granulocyte colony stimulating factor administration is not allowed within 1 week prior to screening assessment). 3. Platelet count ≥ 100×109/L (platelet transfusion is not allowed within 1 week prior to screening assessment). 4. Serum albumin ≥ 2.5 g/dL. 5. TBL ≤ 1.5 × ULN or ≤ 3 × ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinaemia). 6. Except in the setting of HBV, ALT and AST ≤ 2.5 × ULN; for participants with hepatic metastases, ALT and AST ≤ 5 × ULN. See
Exclusion Criteria
1. As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including active bleeding diseases and significant cardiac or psychological conditions), history of allogenic organ transplant, and/or substance abuse which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol. 2. History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected non melanoma skin cancer (basal cell carcinoma of the skin or squamous cell carcinoma of the skin) and curatively treated in situ disease. 3. Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not yet improved to Grade ≤ 1 or baseline. Note: participants may be enrolled with some chronic, stable Grade 2 toxicities (defined as no worsening to Grade \> 2 for at least 3 months prior to the first dose of study intervention and managed with SoC treatment) which the investigator deems related to previous anticancer therapy): 1. Chemotherapy-induced neuropathy 2. Fatigue 3. Residual toxicities from prior immunotherapy treatment: Grade 1 or Grade 2 endocrinopathies, which may include but are not limited to hypothyroidism/hyperthyroidism, Type I diabetes, hyperglycaemia, adrenal insufficiency, or adrenalitis; and skin hypopigmentation (vitiligo) Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention in the opinion of the investigator may be included (eg, hearing loss). 4. Spinal cord compression or brain metastases (unless asymptomatic, stable, and not requiring treatment with corticosteroids or anticonvulsants for at least 2 weeks prior to the first dose of study intervention). Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants must have recovered from the acute toxic effect of radiotherapy (eg, dizziness and signs of increased intracranial pressure). A minimum of 2 weeks must have elapsed between the end of brain radiotherapy and the first dose of study intervention. A minimum of 3 days must have elapsed between the end of corticosteroid therapy for CNS metastatic disease and the first dose of study intervention. 5. Leptomeningeal carcinomatosis or metastasis. 6. Has significant third-space fluid retention (eg, ascites or pleural effusion) and is not amenable for required repeated drainage. 7. Clinically significant corneal disease. 8. Has active or uncontrolled hepatitis B or C virus infection. Participants are eligible if they: 1. Have been curatively treated for HCV infection as demonstrated clinically and by viral serologies 2. Have received HBV vaccination with only anti-HBs positivity and no clinical signs of hepatitis 3. Are HBsAg- and anti-HBc+ (ie, those who have cleared HBV after infection) and meet conditions i-iii of criterion 'd' below: 4. Are HBsAg+ with chronic HBV infection (lasting 6 months or longer) and meet conditions i-iii below: (i) HBV DNA viral load \< 2000 IU/mL (ii) Have normal transaminase values or, if liver metastases are present, abnormal transaminases, with a result of AST/ALT \< 3 × ULN, which are not attributable to HBV infection (iii) Start or maintain antiviral treatment if clinically indicated as per the investigator 9. Known HIV infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA, CD4+ count ≥ 350, no history of AIDS defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on the same anti HIV medications (meaning there are no expected further changes in that time to the number or type of antiretroviral drugs in the regimen). If an HIV infection meets the above criteria, monitoring of viral RNA load and CD4+ count is recommended. Participants must be tested for HIV during the screening period if acceptable by local regulations or an IRB/EC. 10. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections (participants with localised fungal infections of skin or nails are eligible). 11. Known to have active tuberculosis infection (clinical evaluation that may include clinical history, physical examination, and radiographic findings, or tuberculosis testing in line with local practice). 12. Resting ECG with clinically abnormal findings. 13. Uncontrolled or significant cardiac disease including: 1. Myocardial infarction or uncontrolled/unstable angina within 6 months before the first dose of study intervention. 2. Congestive heart failure (New York Heart Association Class II to IV). 3. Uncontrolled hypertension (resting systolic blood pressure \> 180 mmHg or diastolic blood pressure \> 110 mmHg). 4. Cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (NCI CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted based on the investigator judgement with cardiologist consultation recommended. 14. History of non-infectious ILD/pneumonitis, including radiation pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening. 15. Has severe pulmonary function compromise. 16. Prior exposure to the following anticancer therapies: 1. Any TROP2-targeted therapy. 2. Any treatment (including ADC) containing a chemotherapeutic agent targeting topoisomerase I. 3. Any chemotherapy in the metastatic setting. 17. Prior exposure to chloroquine/hydroxychloroquine without an adequate treatment washout period of \> 14 days before the first dose of study intervention. 18. Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, targeted therapy, biologic therapy, tumour embolisation, or monoclonal antibodies ≤ 3 weeks \[for small molecule targeted agents: ≤ 2 weeks or 5 half-lives, whichever is longer, prior to the first dose of study intervention\]). Herbal or natural products intended as treatment or prophylaxis for any type of cancer that may interfere with the activity of the study intervention are excluded. 19. Any concurrent anticancer treatment with the exception of bisphosphonates, denosumab for the treatment of bone metastases. Concurrent use of hormonal therapy for non cancer related conditions (eg, HRT) is allowed. 20. Received prior radiotherapy to the chest within 4 weeks of the start of study intervention or has ongoing radiation-related toxicities requiring corticosteroids. 21. Palliative radiotherapy with a limited field of radiation within ≤ 2 weeks or with wide field of radiation to chest or to more than 30% of the bone marrow within ≤ 4 weeks prior to the first dose of study intervention. 22. Curative radiotherapy; however, palliative radiotherapy for optimal symptom control or pain management is allowed. 23. Concomitant use of chronic systemic (IV or oral) corticosteroids or other immunosuppressive medications \> 10 mg/day of prednisone or equivalent, except for managing AEs; inhaled steroids, intra-articular steroid injections, and other topical steroid formulations are permitted in this study. 24. Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within ≤ 3 weeks of the first dose of study intervention or an anticipated need for major surgery during the study. 25. Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 4 weeks (unless the safety profile is known prior to the first dose of study intervention), enrolment into a prior Dato-DXd study regardless of treatment assignment, or concurrent enrolment in another clinical study (unless the study is observational \[non-interventional\], or the participant is in the follow-up period of an interventional study). 26. Participants with a known history of severe hypersensitivity reactions to either the drug or inactive excipients (including but not limited to polysorbate 80) of Dato-DXd. 27. Participants with a known history of severe hypersensitivity reactions to other monoclonal antibodies. 28. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). 29. Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements. 30. Previous enrolment in the present study. 31. For females only: is pregnant (confirmed with positive serum pregnancy test) or breastfeeding or planning to become pregnant. 32. Female participants should refrain from breastfeeding from enrolment throughout the study and for at least 7 months after last dose of study intervention. 33. Participants for whom the use of steroid-containing mouthwash in contraindicated.

Contacts and Locations

Sponsors and CollaboratorsAstraZeneca
Locations
Research Site | Largo Florida, United States, 33770Research Site | Fort Wayne Indiana, United States, 46825Research Site | Omaha Nebraska, United States, 68130Research Site | New York New York, United States, 10021Research Site | Houston Texas, United States, 77024Research Site | Puyallup Washington, United States, 98373Research Site | Beijing , China, 100021Research Site | Changsha , China, 410013Research Site | Guangzhou , China, 510060Research Site | Linyi , China, 276001Research Site | Shandong , China, 250117Research Site | Wuhan , China, 430071Research Site | Zhengzhou , China, 450008Research Site | Clermont-Ferrand , France, 63050Research Site | La Roche-sur-Yon , France, 85925Research Site | Montpellier , France, 34070Research Site | Paris , France, 75005Research Site | Pierre-Bénite , France, 69310Research Site | Aviano , Italy, 33081Research Site | Florence , Italy, 50134Research Site | Meldola , Italy, 47014Research Site | Milan , Italy, 20141Research Site | Naples , Italy, 80131Research Site | Roma , Italy, 00168Research Site | Bukgu , South Korea, 41404Research Site | Goyang-si , South Korea, 410-769Research Site | Seoul , South Korea, 03080Research Site | Seoul , South Korea, 06273Research Site | Seoul , South Korea, 06351Research Site | Seoul , South Korea, 06591Research Site | Seoul , South Korea, 136705Research Site | Seoul , South Korea, 3722Research Site | Seoul , South Korea, 5505Research Site | A Coruña , Spain, 15006Research Site | Barcelona , Spain, 08035Research Site | Granada , Spain, 18007Research Site | Madrid , Spain, 28033Research Site | Madrid , Spain, 28040Research Site | Seville , Spain, 41009Research Site | Valencia , Spain, 46009