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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Feb 2026 → ongoing

Decision date (initial)

2025-11-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy

To assess efficacy of Dato-DXd by Progression-Free Survival (PFS)

Secondary objectives 5

1. Key secondary objective: To assess the safety of Dato-DXd by the occurrence of select adverse event of special interest (AESIs) and treatment-related severe adverse events (AEs)
2. To assess efficacy of Dato-DXd by assessment of clinical benefit rate (CBR)
3. To further assess efficacy of Dato-DXd by objective response rate (ORR)
4. To further assess efficacy of Dato-DXd by duration of response (DoR)
5. To further assess efficacy of Dato-DXd by assessment of overall survival (OS)

Conditions and MedDRA coding

Locally Advanced Inoperable or Metastatic Breast Cancer Refractory to Endocrine Therapy

Study design 1 period

Regulatory references

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 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).
2. Progressed on and/or not suitable for further endocrine-based therapy per investigator assessment.
3. ECOG performance status of 0 or 1, with no deterioration over the previous 2 weeks prior to the first dose of study intervention.
4. Minimum life expectancy of 12 weeks at screening.
5. Provision of acceptable tumour sample prior to the first dose of study intervention or retrospectively
6. 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.
7. Adequate bone marrow reserve and organ function within 7 days before the first dose of study intervention.
8. Not a candidate for T-DXd, defined as: (a) Participants whose tumours are HER2 IHC 0 with no membrane staining observed (b) Participants whose tumours are HER2-ultralow (IHC 0 with membrane staining that is incomplete and is faint/barely perceptible and in ≤ 10% of tumour cells) and have: (i) comorbidities precluding treatment with T-DXd, or (ii) no access to T-DXd (participant’s country has no regulatory access or no reimbursement at the time of screening)

Exclusion criteria 10

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
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. Active or uncontrolled hepatitis B or C virus infection
7. Known HIV infection that is not well controlled
8. Clinically significant corneal disease
9. History of non-infectious ILD/pneumonitis, including radiation pneumonitis that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
10. Severe pulmonary function compromise

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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. The analysis will include all dosed participants. All events will be included, regardless of whether the participant withdraws from therapy, receives another anticancer therapy, or experiences clinical progression prior to RECIST 1.1.

Secondary endpoints 5

1. Proportion of participants with oral mucositis/stomatitis . Proportion of participants with ocular events. Proportion of participants with Grade 3 or higher AEs possibly related to Dato-DXd treatment (Grade ≥ 3 treatment-related AEs) according to NCI CTCAE 5.0.
2. 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.
3. 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. The analysis will include all dosed participants with measurable disease at baseline.
4. 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.
5. OS defined as the time from the date of the first dose of study intervention until the date of death due to any cause. The analysis will include all dosed participants. All deaths will be included, regardless of whether the participant withdraws from therapy or receives another anticancer therapy. The measure of interest is the OS rate at 6 months.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Center

Third parties 10

Locations

3 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 34 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications