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

NCT07205822 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: D9260C000032025-521904-23-00
• Study Type: interventional
• Target: 100
• Locations: 6 countries
• Sites: 41

Brief Summary

A study to assess the efficacy and safety of Dato-DXd in the pre-chemotherapy setting for patients with metastatic HR-positive, HER2 IHC 0 breast cancer.

Conditions

Breast Cancer

Keywords

HR+, HER2 IHC 0, LA Inoperable/Metastatic, Endo Refractory

Outcome Measures

Primary Outcomes (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.

  From date of first dose of study intervention until disease progression per RECIST 1.1 or death from any cause, whichever occurs first, assessed up to approximately 24 months

Secondary Outcomes (7)

• Proportion of participants with oral mucositis/stomatitis

  From date of first dose of study intervention until 28 days after the last dose (Safety Follow-up)

• Proportion of participants with ocular events

  From date of first dose of study intervention until 28 days after the last dose (Safety Follow-up)

• Proportion of participants with Grade 3 or higher Adverse Events (AEs) possibly related to Dato-DXd treatment

  From date of first dose of study intervention until 28 days after the last dose (Safety Follow-up)

• Clinical benefit rate (CBR) at 24 weeks

  At 24 weeks after first dose

• Objective response rate (ORR)

  From date of first dose until disease progression or death, whichever occurs first, assessed up to approximately 24 months

Study Arms (1)

single arm group

EXPERIMENTAL

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

Interventions

Dato-DXd DRUG

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.

Also known as: IMP administration

single arm group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be ≥ 18 years (and above legal age) at the time of screening.
• 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).
• Progressed on and not suitable for further endocrine therapy per investigator assessment.
• ECOG performance status of 0 or 1, with no deterioration over the previous 2 weeks prior to the first dose of study intervention.
• Minimum life expectancy of 12 weeks at screening.
• 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
• 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.
• Adequate bone marrow reserve and organ function within 7 days before the first dose of study intervention.
• Haemoglobin ≥ 9.0 g/dL (red blood cell/plasma transfusion is not allowed within 1 week prior to screening assessment).
• Absolute neutrophil count ≥ 1.5×109/L (granulocyte colony stimulating factor administration is not allowed within 1 week prior to screening assessment).
• Platelet count ≥ 100×109/L (platelet transfusion is not allowed within 1 week prior to screening assessment).
• Serum albumin ≥ 2.5 g/dL.
• TBL ≤ 1.5 × ULN or ≤ 3 × ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinaemia).
• Calculated CrCL ≥ 30 mL/min as determined by Cockcroft Gault (using actual body weight).
• Male and/or female assigned at birth, inclusive of all gender identities.

You may not qualify if:

• 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.
• 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.
• 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):
• Chemotherapy-induced neuropathy
• Fatigue
• 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).
• 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.
• Leptomeningeal carcinomatosis or metastasis.
• Has significant third-space fluid retention (eg, ascites or pleural effusion) and is not amenable for required repeated drainage.
• Clinically significant corneal disease.
• Has active or uncontrolled hepatitis B or C virus infection. Participants are eligible if they:
• Have been curatively treated for HCV infection as demonstrated clinically and by viral serologies
• Have received HBV vaccination with only anti-HBs positivity and no clinical signs of hepatitis
• Are HBsAg- and anti-HBc+ (ie, those who have cleared HBV after infection) and meet conditions i-iii of criterion 'd' below:
• Are HBsAg+ with chronic HBV infection (lasting 6 months or longer) and meet conditions i-iii below:

Sponsors & Collaborators

• Daiichi Sankyo: collaborator
• AstraZeneca: lead

Study Sites (41)

Research Site

Largo, Florida, 33770, United States

WITHDRAWN

Research Site

Fort Wayne, Indiana, 46825, United States

RECRUITING

Research Site

Omaha, Nebraska, 68130, United States

RECRUITING

Research Site

New York, New York, 10021, United States

NOT YET RECRUITING

Research Site

Houston, Texas, 77024, United States

RECRUITING

Research Site

Puyallup, Washington, 98373, United States

RECRUITING

Research Site

Beijing, 100021, China

RECRUITING

Research Site

Changsha, 410013, China

NOT YET RECRUITING

Research Site

Guangzhou, 510060, China

RECRUITING

Research Site

Linyi, 276001, China

NOT YET RECRUITING

Research Site

Shandong, 250117, China

NOT YET RECRUITING

Research Site

Wuhan, 430071, China

NOT YET RECRUITING

Research Site

Zhengzhou, 450008, China

NOT YET RECRUITING

Research Site

Clermont-Ferrand, 63050, France

RECRUITING

Research Site

La Roche-sur-Yon, 85925, France

RECRUITING

Research Site

Montpellier, 34070, France

RECRUITING

Research Site

Paris, 75005, France

RECRUITING

Research Site

Pierre-Bénite, 69310, France

RECRUITING

Research Site

Aviano, 33081, Italy

RECRUITING

Research Site

Florence, 50134, Italy

RECRUITING

Research Site

Meldola, 47014, Italy

RECRUITING

Research Site

Milan, 20141, Italy

RECRUITING

Research Site

Naples, 80131, Italy

RECRUITING

Research Site

Roma, 00168, Italy

NOT YET RECRUITING

Research Site

Bukgu, 41404, South Korea

RECRUITING

Research Site

Goyang-si, 410-769, South Korea

NOT YET RECRUITING

Research Site

Seoul, 03080, South Korea

RECRUITING

Research Site

Seoul, 06273, South Korea

RECRUITING

Research Site

Seoul, 06351, South Korea

RECRUITING

Research Site

Seoul, 06591, South Korea

RECRUITING

Research Site

Seoul, 136705, South Korea

RECRUITING

Research Site

Seoul, 3722, South Korea

RECRUITING

Research Site

Seoul, 5505, South Korea

RECRUITING

Research Site

A Coruña, 15006, Spain

NOT YET RECRUITING

Research Site

Barcelona, 08035, Spain

RECRUITING

Research Site

Granada, 18007, Spain

NOT YET RECRUITING

Research Site

Madrid, 28033, Spain

NOT YET RECRUITING

Research Site

Madrid, 28040, Spain

NOT YET RECRUITING

Research Site

Madrid, 28040, Spain

RECRUITING

Research Site

Seville, 41009, Spain

NOT YET RECRUITING

Research Site

Valencia, 46009, Spain

NOT YET RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2025
• First Posted: October 3, 2025
• Study Start: October 30, 2025
• Primary Completion (Estimated): February 2, 2028
• Study Completion (Estimated): February 2, 2028
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

KR (9); IT (6); ES (8); US (6); CN (7); FR (5)