DATO-BASE: DATOpotamab-deruxtecan for Breast Cancer Brain metAstaSEs

NCT06176261 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 23-533
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to test the safety and effectiveness of the study drug datopotamab deruxtecan in participants with metastatic breast cancer that has spread to the brain. The name of the study drug used in this research study is: Datopotamab deruxtecan (a type of antibody-drug conjugate)

Conditions

Breast Cancer; Breast Cancer Female; Metastatic Triple-Negative Breast Carcinoma; ER Positive Breast Cancer; HER2-negative Breast Cancer; HER2 Negative Breast Carcinoma; ER-negative Breast Cancer

Keywords

Breast Cancer; Breast Cancer Female; Metastatic Triple-Negative Breast Carcinoma; ER Positive Breast Cancer; HER2 Negative Breast Cancer; HER2 Negative Breast Carcinoma; ER Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) in RANO-BM Criteria

  The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RANO-BM criteria defined protocol section 11.1.1.

  3 years

Secondary Outcomes (7)

• Objective Response Rate (ORR)

  3 years

• Clinical Benefit Rate at 18 weeks (CBR18)

  18 Weeks

• Clinical Benefit Rate at 24 weeks (CBR24)

  24 Weeks

• Median Progression-Free Survival (PFS)

  Assessed from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, up to 3 years

• Median Overall Survival (OS)

  Assessed from date of enrollment until the date of death from any cause, up to 3 years

Study Arms (3)

Cohort A: Estrogen Receptor Positive HER2-Negative Metastatic Breast Cancer

EXPERIMENTAL

24 participants will be enrolled and will complete study procedures as outlined below: * Baseline visit with optional CSF collection via lumbar puncture and assessments. * CT or MRI scans every 6 weeks for 24 weeks, then every 9 weeks. * Cycle 1 Through End of Treatment: --Day 1 of 21 day cycle: Predetermined dose of Datopotamab Deruxtecan 1x daily. * End of Treatment: * Follow up every 6 months. * Optional CSF collection via lumbar puncture. * CT or MRI scans every 12 weeks.

Drug: Datopotamab Deruxtecan

Cohort B: Metastatic Triple-Negative Breast Cancer

EXPERIMENTAL

24 participants will be enrolled and will complete study procedures as outlined below: * Baseline visit with optional CSF collection via lumbar puncture and assessments. * CT or MRI scans every 6 weeks for 24 weeks, then every 9 weeks. * Cycle 1 Through End of Treatment: --Day 1 of 21 day cycle: Predetermined dose of Datopotamab Deruxtecan 1x daily. * End of Treatment: * Follow up every 6 months. * Optional CSF collection via lumbar puncture. * CT or MRI scans every 12 weeks.

Drug: Datopotamab Deruxtecan

Cohort C: HER2-Negative Metastatic Breast Cancer (any ER Expression) with Leptomeningeal Metastases

EXPERIMENTAL

* Baseline visit with CSF collection via lumbar puncture and assessments. * CT or MRI scans every 6 weeks for 24 weeks, then every 9 weeks. * Cycle 1 --Day 1 of 21 day cycle: Predetermined dose of Datopotamab Deruxtecan 1x daily. * Cycle 2 * Day 1 of 21 day cycle: Predetermined dose of Dato-DXd 1x daily. * Day 2 of 21 day cycle: CSF collection. * Cycle 3 Through End of Treatment: --Day 1 of 21 day cycle: Predetermined dose of Datopotamab Deruxtecan 1x daily. * End of Treatment: * Follow up every 6 months. * Optional CSF collection via lumbar puncture. * CT or MRI scans every 12 weeks.

Drug: Datopotamab Deruxtecan

Interventions

Datopotamab Deruxtecan DRUG

Antibody-drug conjugate, 100 mg single-use vial, via intravenous infusion per protocol.

Also known as: DS-1062; DS-1062a, Dato-DXd

Cohort A: Estrogen Receptor Positive HER2-Negative Metastatic Breast Cancer; Cohort B: Metastatic Triple-Negative Breast Cancer; Cohort C: HER2-Negative Metastatic Breast Cancer (any ER Expression) with Leptomeningeal Metastases

Eligibility Criteria

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

You may qualify if:

• Metastatic breast cancer that is pathologically confirmed to be HER2-negative according to 2018 ASCO/CAP guidelines 55.
• Radiological confirmation of metastatic disease.
• Cohorts A and B: Presence of newly diagnosed brain metastases or brain metastases progressing after prior local and/or systemic therapy.
• Cohorts A and B: Participants must have a baseline MRI of the brain performed with and without gadolinium contrast, and must have central nervous system metastases with at least one measurable brain metastasis ≥ 1.0 cm in size (per RANO-BM) that has not been irradiated, or has progressed despite prior radiation therapy and/or systemic therapy (in the opinion of the treating physician). For cohorts A and B, head CT with contrast may be used in place of MRI at baseline and throughout the trial if MRI is contraindicated and the participant's CNS metastases are clearly measurable by head CT.
• Cohorts C: Radiological evidence of evaluable leptomeningeal disease and clinical diagnosis of LMD per treating investigator. A positive CSF cytology is not required.
• Cohort A: prior progression to treatment with at least one line of endocrine treatment (with or without CDK4/6 inhibition) in the metastatic setting is mandatory. Patients experiencing recurrence during adjuvant endocrine treatment will be also considered eligible for the trial. There is no limit on the number of prior lines acceptable for the purpose of enrollment in this study.
• Cohort B and C: no prior treatment is required (i.e., previously untreated patients are eligible). There is no limit on the number of prior lines of therapy acceptable for the purpose of enrollment in this study.
• Participants may have measurable or non-measurable extracranial disease. Participants are NOT required to have extracranial disease, but must have imaging done to document disease status at baseline.
• Age ≥ 18 years.
• ECOG Performance Status 0-2
• Participants must have adequate treatment washout period before registration, defined as \> 4 weeks from major surgery, \> 2 weeks from radiation treatment. For weekly chemotherapy regimens, \> 2 weeks from chemotherapy; for every 3 weekly regimens, \> 3 weeks from chemotherapy. At least 2 weeks from other systemic or targeted or investigational therapies (other than endocrine therapy) for breast cancer. No washout is required for endocrine therapy (e.g. aromatase inhibitors, tamoxifen, fulvestrant) but patients should discontinue prior to start of protocol therapy. Patients on ovarian suppression are allowed (but not required) to continue ovarian suppression at the discretion of their treating provider.
• Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan.
• Adequate organ function as defined by the following values:
• Hemoglobin ≥ 9.0 g/dL. Red blood cell/plasma transfusion is not permitted within 1 week prior to screening assessment.
• Absolute neutrophil count ≥1,500/mm3. Granulocyte colony-stimulating factor administration is not permitted within 1 week prior to screening assessment.

You may not qualify if:

• Visceral crisis or impending visceral crisis
• CNS complications for whom urgent neurosurgical intervention is indicated (i.e., resection, shunt placement)
• Indication for immediate local therapy to CNS lesion(s) as defined by local standard
• Evidence of significant (i.e., symptomatic) intracranial hemorrhage
• \> 2 seizures within 4 weeks prior to study entry (registration)
• Ongoing/persistent toxicities caused by previous anti-cancer therapy (except alopecia) not yet improved to Grade ≤ 1 OR baseline prior to study entry (registration)
• Known contraindication to MRI (e.g., due to pacemaker, ferromagnetic implants, claustrophobia, extreme obesity, hypersensitivity). However, for cohorts A and B, head CT with contrast may be used in place of MRI at baseline and throughout the trial if MRI is contraindicated and the participant's CNS metastases are clearly measurable by head CT.
• Concurrent administration of other anti-cancer therapy during the course of this study is not allowed. Concurrent use of supportive care medications is allowed, and certain medications are required (see Section 5.1).
• Uncontrolled intercurrent illness, including (but not limited to) active infection, severely compromised pulmonary function, unstable angina pectoris, uncontrolled cardiac arrhythmia, active ischemic heart disease, myocardial infarction within the previous six months, gastric or duodenal ulceration diagnosed within the previous six months, chronic liver or renal disease, or severe malnutrition. Note that if a patient has controlled diabetes mellitus, but is unable to monitor blood glucose at home, they will be excluded from the trial.
• Participants must not have a condition requiring ongoing systemic treatment with corticosteroids (\>4 mg daily dexamethasone (or bioequivalent)) or other immunosuppressive medications within 7 days prior to the baseline MRI. Corticosteroids administration must be stable and planned to remain ≤ 4 mg daily for the duration of protocol treatment. However, use of corticosteroids for clinical symptoms is allowed based upon treating physician discretion.
• History of non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
• A history of uncontrolled seizures, CNS disorders, or psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs.
• A history of malignancy other than breast cancer, except (a) adequately resected non-melanoma skin cancer, (b) curatively treated in situ disease, or (c) other solid tumors curatively treated, with no evidence of disease for ≥ 3 years.
• Major surgery, open biopsy, or significant traumatic injury within 28 days prior to the initiation of protocol therapy, or anticipation of need for a major surgical procedure during the study.
• Clinically significant corneal disease.

Sponsors & Collaborators

• Sarah Sammons, MD: lead
• Daiichi Sankyo: collaborator

Study Sites (3)

Miami Baptist Cancer Institute/

Miami, Florida, 33176, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Sarah Sammons, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah Sammons, MD

CONTACT

617-362-3800; sarahl_sammons@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 7, 2023
• First Posted: December 19, 2023
• Study Start: January 8, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: July 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (3)