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

Trial Summary

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.

What data supports the effectiveness of the drug Datopotamab Deruxtecan for breast cancer with brain metastases?

Datopotamab Deruxtecan has shown promising results in other types of breast cancer and non-small cell lung cancer, with some patients experiencing tumor shrinkage and manageable side effects. In particular, it demonstrated encouraging response rates in patients with advanced triple-negative breast cancer and non-small cell lung cancer. ^{1 2 3 4 5}

What makes the drug Datopotamab Deruxtecan unique for treating breast cancer with brain metastases?

Datopotamab Deruxtecan is unique because it is a TROP2-directed antibody-drug conjugate, which means it specifically targets a protein called TROP2 on cancer cells and delivers a powerful chemotherapy agent directly to them, potentially offering a more targeted approach compared to traditional chemotherapy. ^{1 2 3 6 7}

What is the purpose of this trial?

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)

Research Team

Sarah Sammons, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

TROPION-Breast01: Datopotamab deruxtecan vs chemotherapy in pre-treated inoperable or metastatic HR+/HER2- breast cancer. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

TROP2 ADC Intrigues in NSCLC. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

TROPION-Breast02: Datopotamab deruxtecan for locally recurrent inoperable or metastatic triple-negative breast cancer. [2023]

5. United States 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. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Brain Metastasis from HER2-Positive Breast Cancer: An Evolving Landscape. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial. [2022]