A Phase-3, Open-Label, Randomized Study of Dato-DXd Versus Investigator's Choice of Chemotherapy (ICC) in Participants With Inoperable or Metastatic HR-Positive, HER2-Negative Breast Cancer Who Have Been Treated With One or Two Prior Lines of Systemic Chemotherapy (TROPION-Breast01)

Running, not enrolling · Phase 3

Conditions studied: Breast Cancer

In brief

The study will evaluate the safety and efficacy of datopotamab deruxtecan (also known as Dato-DXd, DS-1062a), when compared with Investigator's choice of standard of care single-agent chemotherapy (eribulin, capecitabine, vinorelbine, or gemcitabine) in participants with inoperable or metastatic HR-positive, HER2- negative breast cancer who have been treated with one or two prior lines of systemic chemotherapy.

Key facts

Study ID

NCT05104866

Run by

AstraZeneca

People needed

732

Starts

2021-10-18

Expected to finish

2026-07-31

Last updated by the study team

2026-05-05

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age • Participant must be ≥ 18 years at the time of screening.
• Type of Participant and Disease Characteristics
• Inoperable or metastatic HR+, HER2-negative breast cancer
• Progressed on and not suitable for endocrine therapy per investigator assessment and treated with 1 to 2 lines of prior chemotherapy in the inoperable/metastatic setting. Participant must have documented progression on their most recent line of chemotherapy.
• Eligible for one of the chemotherapy options listed as ICC (eribulin, capecitabine, vinorelbine, gemcitabine), per investigator assessment.
• ECOG PS of 0 or 1, with no deterioration over the previous 2 weeks prior to day of first dosing.
• At least 1 measurable lesion not previously irradiated that qualifies as a RECIST 1.1. Note: Participants with bone-only metastases are not permitted.
• Participants with a history of previously treated neoplastic spinal cord compression, or clinically inactive brain metastases, who require no treatment with corticosteroids or anticonvulsants, may be included in the study, if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of radiotherapy and study enrolment.
• Adequate organ and bone marrow function within 7 days before day of first dosing as follows:
• Hemoglobin: ≥ 9.0 g/L.
• Absolute neutrophil count: 1500/mm3.
• Platelet count: 100000/mm3. • Total bilirubin: ≤ 1.5 × ULN if no liver metastases; or ≤ 3 × ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline.
• ALT and AST: ≤ 3 × ULN for AST/ALT; however, if elevation is due to liver metastases, ≤ 5.0 × ULN is allowed.
• Calculated creatinine clearance: ≥ 30 mL/min as calculated using the Cockcroft-Gault equation (using actual body weight).
• LVEF ≥ 50% by either an echocardiogram or MUGA within 28 days of first dosing.
• Has had an adequate treatment washout period before Cycle 1 Day 1, defined as:
• Major surgery: ≥ 3 weeks.
• Radiation therapy including palliative radiation to chest: ≥ 4 weeks (palliative radiation therapy to other areas ≥ 2 weeks).
• Anticancer therapy including hormonal therapy: ≥ 3 weeks (for small molecule targeted agents: ≥ 2 weeks or 5 half-lives, whichever is longer).
• Antibody-based anticancer therapy: ≥ 4 weeks with the exception of receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors (eg, denosumab for the treatment of bone metastases).
• Immunotherapy (non-antibody-based therapy): ≥ 2 weeks or 5 times the terminal elimination T½ of the agent, whichever is longer.
• Chloroquine/hydroxychloroquine: > 14 days.
• Have available a FFPE tumor sample (block preferred, or a minimum of 20 freshly cut slides), at the time of screening. Note: Sample collection in China will comply with local regulatory approval.
• Minimum life expectancy of 12 weeks at screening.
• Sex

You may not qualify if…

• Medical Conditions
• Any evidence of diseases which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize 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 basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy, adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated.
• Persistent toxicities caused by previous anticancer therapy (excluding alopecia), not yet improved to CTCAE Version 5.0 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 first dosing and managed with SoC treatment) which the investigator deems related to previous anticancer therapy.
• Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections.
• Known active or uncontrolled hepatitis B or C infection; or positive for hepatitis B or C virus based on the evaluation of results of tests for hepatitis B (HBsAg, anti-HBs, anti-HBc, or HBV DNA) or hepatitis C (HCV antibody or HCV RNA) infection at screening.
• Known HIV infection that is not well controlled.
• Uncontrolled or significant cardiac disease, including myocardial infarction or uncontrolled/unstable angina within 6 months prior to C1D1, CHF (New York Heart Association Class II to IV), uncontrolled or significant cardiac arrhythmia, or uncontrolled hypertension (resting systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg).
• Investigator judgment of 1 or more of the following:
• Mean resting corrected QTcF interval > 470 ms , obtained from triplicate ECGs performed at screening.
• History of QT prolongation associated with other medications that required discontinuation of that medication, or any current concomitant medication known to prolong the QT interval and cause Torsades de Pointes.
• Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.
• History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement, or prior pneumonectomy.
• Leptomeningeal carcinomatosis.
• Clinically significant corneal disease.
• Known active tuberculosis infection
• Prior/Concomitant Therapy
• Any of the following prior anticancer therapies:
• Any treatment (including ADC) containing a chemotherapeutic agent targeting topoisomerase I
• TROP2-targeted therapy
• Prior treatment with same ICC agent
• Any concurrent anticancer treatment, with the exception of bisphosphonates, denosumab, for the treatment of bone metastases.
• Concurrent use of systemic hormonal replacement therapy (eg, estrogen). However, concurrent use of hormones for non-cancer related conditions (eg, insulin for diabetes) is acceptable.
• 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.

Where it is running

• Research Site — Los Angeles, California, United States
• Research Site — Palo Alto, California, United States
• Research Site — San Francisco, California, United States
• Research Site — Jacksonville, Florida, United States
• Research Site — Atlanta, Georgia, United States
• Research Site — Boston, Massachusetts, United States
• Research Site — Boston, Massachusetts, United States
• Research Site — Grand Rapids, Michigan, United States
• Research Site — New York, New York, United States
• Research Site — Cleveland, Ohio, United States
• Research Site — Portland, Oregon, United States
• Research Site — Nashville, Tennessee, United States
• Research Site — Richmond, Virginia, United States
• Research Site — CABA, Argentina
• Research Site — Ciudad de Buenos Aires, Argentina
• Research Site — La Plata, Argentina
• Research Site — Mar del Plata, Argentina
• Research Site — Rosario, Argentina
• Research Site — Rosario, Argentina
• Research Site — Anderlecht, Belgium
• Research Site — Leuven, Belgium
• Research Site — Liège, Belgium
• Research Site — Itajaí, Brazil
• Research Site — Jaú, Brazil
• Research Site — Duarte, California, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.