Datopotamab Deruxtecan for Breast Cancer with Brain Metastases

Recruiting in Palo Alto (17 mi)

+3 other locations

Overseen by Sarah Sammons, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Sarah Sammons, MD

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Visceral crisis, CNS complications, others

No Placebo Group

Prior Safety Data

Trial Summary

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)

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.

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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.

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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.

Trial 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

Participant Groups

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.

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Miami Baptist Cancer Institute/ Miami, FL

Duke University Medical Center Durham, NC

Brigham and Women's Hospital Boston, MA

Dana-Farber Cancer Institute Boston, MA

Who Is Running the Clinical Trial?

Sarah Sammons, MD Lead Sponsor

Daiichi Sankyo Industry Sponsor

Daiichi Sankyo, Inc. Industry Sponsor

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] Improving the prognosis for patients with metastatic HR+/HER2- breast cancer remains an unmet need. Patients with tumors that have progressed on endocrine therapy and/or are not eligible for endocrine therapy had limited treatment options beyond chemotherapy. Antibody-drug conjugates are a novel and promising treatment class in this setting. Datopotamab deruxtecan (Dato-DXd) consists of a TROP2-directed humanized IgG1 monoclonal antibody attached via a serum-stable cleavable linker to a topoisomerase I inhibitor payload. TROPION-Breast01 is an ongoing phase 3 study that is evaluating the efficacy and safety of Dato-DXd compared with investigator's choice of standard-of-care chemotherapy in patients with inoperable or metastatic HR+/HER2- breast cancer who have received one or two prior lines of systemic chemotherapy in the inoperable or metastatic setting. Clinical Trial Registration: NCT05104866 (ClinicalTrials.gov).

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

TROP2 ADC Intrigues in NSCLC. [2021] The TROP2-directed antibody-drug conjugate datopotamab deruxtecan may be active in patients with advanced or metastatic non-small cell lung cancer, according to preliminary findings. In a phase I trial, the agent elicited responses in almost a quarter of patients and had manageable side effects.

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

"Very Compelling" Results for ADC in TNBC Trial. [2022] In a phase I trial, the antibody-drug conjugate datopotamab deruxtecan demonstrated encouraging response rates and manageable toxicity in patients with advanced/metastatic triple-negative breast cancer that has recurred after, or is resistant to, multiple therapies. Overall, 34% of patients experienced a complete or partial response.

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

TROPION-Breast02: Datopotamab deruxtecan for locally recurrent inoperable or metastatic triple-negative breast cancer. [2023] Despite recent treatment advances, the prognosis for patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) remains poor. The antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) is composed of a humanized anti-TROP2 IgG1 monoclonal antibody linked to a topoisomerase I inhibitor payload via a stable, cleavable linker. The phase III TROPION-Breast02 trial in patients previously untreated for locally recurrent inoperable or metastatic TNBC, who are not candidates for PD-1/PD-L1 inhibitors is evaluating efficacy and safety of Dato-DXd versus investigator's choice of chemotherapy (ICC). Approximately 600 patients will be randomized 1:1 to Dato-DXd 6 mg/kg iv. every 3 weeks or ICC (paclitaxel, nab-paclitaxel, carboplatin, capecitabine or eribulin mesylate). Dual primary end points are progression-free survival by blinded independent central review and overall survival.

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] This first-in-human, dose-escalation and dose-expansion study evaluated the safety, tolerability, and antitumor activity of datopotamab deruxtecan (Dato-DXd), a novel trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate in solid tumors, including advanced non-small-cell lung cancer (NSCLC).

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

Brain Metastasis from HER2-Positive Breast Cancer: An Evolving Landscape. [2023] Trastuzumab deruxtecan is a HER2-directed antibody-drug conjugate with ability to cross the blood-tumor barrier and activity on brain metastases. To test the activity of new drugs, patient-derived xenograft models from human brain metastases and phase 0 and window-of-opportunity trials are of utmost importance. See related article by Kabraji et al., p. 174.

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] Trastuzumab deruxtecan is an antibody-drug conjugate with high extracranial activity in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. We conducted the prospective, open-label, single-arm, phase 2 TUXEDO-1 trial. We enrolled patients aged ≥18 years with HER2-positive breast cancer and newly diagnosed untreated brain metastases or brain metastases progressing after previous local therapy, previous exposure to trastuzumab and pertuzumab and no indication for immediate local therapy. Patients received trastuzumab deruxtecan intravenously at the standard dose of 5.4 mg per kg bodyweight once every 3 weeks. The primary endpoint was intracranial response rate measured according to the response assessment in neuro-oncology brain metastases criteria. A Simon two-stage design was used to compare a null hypothesis of