Datopotamab Deruxtecan for Breast Cancer with Brain Metastases

Recruiting at 3 trial locations

Overseen By Sarah Sammons, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sarah Sammons, MD

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Visceral crisis, CNS complications, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 13

Duration: 24 weeks

58 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called datopotamab deruxtecan, a TROP2-directed antibody-drug conjugate, for individuals with breast cancer that has spread to the brain. The main goal is to determine the treatment's safety and effectiveness. The trial includes different groups, such as those with triple-negative breast cancer or estrogen receptor-positive breast cancer. Participants must have metastatic breast cancer that is HER2-negative with confirmed brain involvement. This trial may suit individuals whose breast cancer has spread to the brain, particularly if it has worsened after other treatments. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of at least 2 weeks for most systemic or targeted therapies, but no washout is needed for endocrine therapy, although it should be stopped before starting the trial. You can continue ovarian suppression if your doctor agrees.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research shows that datopotamab deruxtecan is generally well-tolerated by patients with advanced breast cancer. Studies indicate that most patients experience side effects that are not too severe. Specifically, trials involving patients who have undergone extensive treatment for advanced breast cancer have shown promising results with this drug.

While any treatment can have side effects, current data suggests that datopotamab deruxtecan is safe enough for clinical use. However, the drug remains under investigation, making ongoing research crucial to confirm its safety. Researchers closely monitor participants in clinical trials to manage any side effects that may occur. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Datopotamab Deruxtecan is unique because it uses a novel approach to target cancer cells. Unlike traditional chemotherapy, which attacks both cancerous and healthy cells, this treatment combines a targeted therapy with a chemotherapy agent. It specifically delivers chemotherapy directly to cancer cells, potentially reducing side effects and improving effectiveness. Researchers are excited about its potential to treat breast cancer that has spread to the brain, especially since current options for brain metastases, like surgery and radiation, can be limited by the blood-brain barrier.

What evidence suggests that datopotamab deruxtecan might be an effective treatment for metastatic breast cancer with brain metastases?

Research has shown that datopotamab deruxtecan holds promise for treating various types of breast cancer. In this trial, participants with metastatic triple-negative breast cancer in Cohort B will receive this drug, which extended patients' lives by five months compared to standard chemotherapy in previous studies. Cohort A includes patients with estrogen receptor-positive, HER2-negative breast cancer, where the drug demonstrated good effectiveness and manageable side effects. For participants in Cohort C with HER2-negative breast cancer that has spread to the brain, the drug aims to extend life without worsening cancer. This treatment targets cancer cells directly, delivering chemotherapy to them, which may enhance effectiveness and reduce side effects. ^{6 7 8 9 10}

Who Is on the Research Team?

Sarah Sammons, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic breast cancer that has spread to the brain. Specific details about who can join are not provided, but typically participants must meet certain health standards and may be required to have a particular type of breast cancer.

Inclusion Criteria

Radiological confirmation of metastatic disease

I have new or worsening brain metastases.

I have a brain tumor larger than 1.0 cm, confirmed by an MRI with contrast.

Exclusion Criteria

I am a man who is either surgically sterile or using contraception, and I do not donate sperm.

I am a woman who is post-menopausal, surgically sterile, or using effective birth control.

I need urgent brain surgery due to complications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Datopotamab Deruxtecan with CT or MRI scans every 6 weeks for 24 weeks, then every 9 weeks

24 weeks

CT or MRI scans every 6 weeks

End of Treatment

Follow-up every 6 months with optional CSF collection and CT or MRI scans every 12 weeks

Long-term

Follow-up every 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Datopotamab Deruxtecan

Trial Overview The study is testing datopotamab deruxtecan, an antibody-drug conjugate, for its safety and effectiveness in treating patients whose breast cancer has metastasized to the brain.

How Is the Trial Designed?

Group I: Cohort C: HER2-Negative Metastatic Breast Cancer (any ER Expression) with Leptomeningeal Metastases Experimental Treatment 1 Intervention

* 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.

Group II: Cohort B: Metastatic Triple-Negative Breast Cancer Experimental Treatment 1 Intervention

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.

Group III: Cohort A: Estrogen Receptor Positive HER2-Negative Metastatic Breast Cancer Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Sarah Sammons, MD

Lead Sponsor

Trials

3

Recruited

110+

Daiichi Sankyo

Industry Sponsor

Trials

443

Recruited

493,000+

Hiroyuki Okuzawa

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

MD

Daiichi Sankyo, Inc.

Industry Sponsor

Trials

390

Recruited

442,000+

Yuki Abe

Daiichi Sankyo, Inc.

Chief Medical Officer since 2022

MD

Hiroyuki Okuzawa

Daiichi Sankyo, Inc.

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Published Research Related to This Trial

In a phase I trial, the TROP2-directed antibody-drug conjugate datopotamab deruxtecan showed promising activity in patients with advanced or metastatic non-small cell lung cancer, with nearly 25% of participants responding to the treatment.

The treatment was associated with manageable side effects, suggesting it could be a safe option for patients with this type of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TROP2 ADC Intrigues in NSCLC. [2021]

Datopotamab deruxtecan (Dato-DXd) demonstrated promising antitumor activity in patients with advanced non-small-cell lung cancer (NSCLC), achieving an objective response rate of 26% and a median duration of response of 10.5 months in a study involving 210 patients.

The treatment was generally well-tolerated, with a maximum tolerated dose of 8 mg/kg and a recommended dose of 6 mg/kg, although some patients experienced treatment-emergent adverse events, including nausea and interstitial lung disease, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human, Phase I Dose-Escalation and Dose-Expansion Study of Trophoblast Cell-Surface Antigen 2-Directed Antibody-Drug Conjugate Datopotamab Deruxtecan in Non-Small-Cell Lung Cancer: TROPION-PanTumor01. Shimizu, T., Sands, J., Yoh, K., et al.[2023]

Datopotamab deruxtecan (Dato-DXd) is a promising new treatment for patients with metastatic HR+/HER2- breast cancer, particularly for those who have limited options after endocrine therapy and chemotherapy.

The ongoing phase III TROPION-Breast01 study is comparing the efficacy and safety of Dato-DXd against standard chemotherapy in patients who have already received one or two lines of systemic treatment, aiming to improve outcomes in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TROPION-Breast01: Datopotamab deruxtecan vs chemotherapy in pre-treated inoperable or metastatic HR+/HER2- breast cancer. Bardia, A., Jhaveri, K., Kalinsky, K., et al.[2023]

In a phase I trial, datopotamab deruxtecan showed promising response rates, with 34% of patients with advanced or metastatic triple-negative breast cancer experiencing a complete or partial response.

The treatment was found to have manageable toxicity, indicating it may be a safe option for patients who have not responded to multiple previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Very Compelling" Results for ADC in TNBC Trial. [2022]

In the TUXEDO-1 trial involving 15 patients with HER2-positive breast cancer and brain metastases, trastuzumab deruxtecan achieved a high overall intracranial response rate of 73.3%, indicating its efficacy in treating this challenging condition.

The treatment was well-tolerated, with no new safety concerns reported, and patients maintained their quality of life and cognitive functioning throughout the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial. Bartsch, R., Berghoff, AS., Furtner, J., et al.[2022]

The phase III TROPION-Breast02 trial is investigating the efficacy and safety of the antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) in approximately 600 patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) who have not received prior treatment.

Dato-DXd is designed to target TROP2 and deliver a topoisomerase I inhibitor directly to cancer cells, and the trial will compare its effectiveness against standard chemotherapy options, focusing on progression-free survival and overall survival as primary outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TROPION-Breast02: Datopotamab deruxtecan for locally recurrent inoperable or metastatic triple-negative breast cancer. Dent, RA., Cescon, DW., Bachelot, T., et al.[2023]

Trastuzumab deruxtecan is an innovative HER2-targeted therapy that can effectively penetrate the blood-tumor barrier, making it a promising option for treating brain metastases.

The use of patient-derived xenograft models and early-phase trials is crucial for evaluating the effectiveness of new treatments like trastuzumab deruxtecan in targeting brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain Metastasis from HER2-Positive Breast Cancer: An Evolving Landscape. Soffietti, R., Pellerino, A.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01909

Datopotamab Deruxtecan in Advanced or Metastatic HR+ ... In patients with heavily pretreated advanced HR+/HER2– BC and TNBC, Dato-DXd demonstrated promising clinical activity and a manageable safety profile.

2. datrowayhcp.com datrowayhcp.com/hr-positive-her2-negative-mbc/efficacy/study-design

Study Design & Baseline Characteristics - Datroway Unresectable or Metastatic, HR-Positive, HER2-Negative Breast Cancer. TROPION-Breast01. The safety of DATROWAY was evaluated in 360 patients with unresectable ...

3. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/DATROWAY-datopotamab-deruxtecan-dlnk-demonstrated-an-unprecedented-median-overall-survival-improvement-of-five-months-vs-chemotherapy-as-1st-line-treatment-for-patients-with-metastatic-triple-negative-breast-cancer-for-whom-immunotherapy-was-not-an-option-in-TROPION-Breast02.html

DATROWAY® (datopotamab deruxtecan-dlnk) ... AstraZeneca and Daiichi Sankyo's DATROWAY also demonstrated a highly statistically significant and clinically meaningful 43% reduction in ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06533826

TReatment of ADC-Refractory Breast CancEr With Dato- ... The purpose of this study is to test the safety and effectiveness of the sequence of two investigational drugs (trastuzumab deruxtecan followed by ...

5. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2025/datroway-demonstrated-an-unprecedented-median-overall-survival-improvement-of-five-months-vs-chemotherapy-as-1st-line-treatment-for-patients-with-metastatic-triple-negative-breast-cancer-for-whom-immunotherapy-was-not-an-option-in-tropion-breast02.html

Datroway demonstrated an unprecedented median overall ... Datroway demonstrated an unprecedented median overall survival improvement of five months vs. chemotherapy as 1st-line treatment for patients ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05104866

Study Details | NCT05104866 | A Phase-3, Open-Label, ... This study aims to see if datopotamab deruxtecan allows patients to live longer without their breast cancer getting worse, or simply to live longer.

7. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/DATROWAY-datopotamab-deruxtecan-dlnk-demonstrated-statistically-significant-and-clinically-meaningful-improvement-in-overall-survival-as-1st-line-therapy-for-patients-with-metastatic-triple-negative-breast-cancer-for-whom-immunotherapy-was-not-an-option-in-TROPION-Breast02.html

DATROWAY® (datopotamab deruxtecan-dlnk) ... AstraZeneca and Daiichi Sankyo's DATROWAY is the first and only therapy to significantly improve overall survival vs. chemotherapy in this ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38652877/

and Triple-Negative Breast Cancer: Results From the Phase I ... In patients with heavily pretreated advanced HR+/HER2- BC and TNBC, Dato-DXd demonstrated promising clinical activity and a manageable safety profile.

9. dukehealth.org dukehealth.org/clinical-trials/directory/pro00115812

Clinical Trial - DF/HCC 23-533 DATO-BASE for Breast... We are doing this study to test the safety and effectiveness of the study drug, datopotamab deruxtecan (also known as dato-DXd), and find out if it is a ...

10. asco.org asco.org/abstracts-presentations/ABSTRACT488486

DATO-Base: A phase II study of DATOpotamab deruxtecan ... DATO-Base is an ongoing, open label, multicenter, investigator-initiated phase II trial for patients with HER2-negative MBC with active BCBM and/or LMD.