Trastuzumab Deruxtecan for Metastatic Breast Cancer

Not currently recruiting at 265 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Daiichi Sankyo

Must not be taking: Anti-HER2 therapy

Disqualifiers: High-HER2 expression, Cardiovascular disease, CNS metastases, ILD/pneumonitis, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, trastuzumab deruxtecan, to determine if it outperforms standard treatments for a specific type of breast cancer. The focus is on individuals whose breast cancer has low HER2 protein, is inoperable, and has metastasized. Participants should have previously tried chemotherapy without success. The trial will compare the new treatment to other common options selected by doctors. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to access a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that trastuzumab deruxtecan is usually well-tolerated by people with HER2-low metastatic breast cancer. In a study with 371 patients, most side effects were mild to moderate, indicating they were not very serious.

Common side effects include nausea, tiredness, and low blood cell counts, which are typical for many cancer treatments. Trastuzumab deruxtecan has undergone thorough study, providing doctors with a good understanding of what to expect.

While the treatment is generally safe, individual reactions can vary. Consulting a doctor can help determine if this treatment is suitable. ^{1 2 3 4 5}

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

Trastuzumab deruxtecan is unique because it targets HER2-low expressing metastatic breast cancer cells with a precision not seen in traditional chemotherapy options like capecitabine, eribulin, or paclitaxel. This treatment is an antibody-drug conjugate, combining the targeted action of monoclonal antibodies with the cancer-killing power of chemotherapy, allowing it to deliver its potent payload directly to cancer cells while sparing more healthy cells. Researchers are excited about trastuzumab deruxtecan because its targeted mechanism could lead to improved outcomes and fewer side effects for patients with limited treatment options.

What evidence suggests that this trial's treatments could be effective for metastatic breast cancer?

Studies have shown that trastuzumab deruxtecan, which participants in this trial may receive, effectively treats HER2-low metastatic breast cancer. Earlier research demonstrated that patients taking this drug lived longer without their cancer worsening or spreading. Specifically, their cancer did not progress for an average of 13.2 months, compared to 8.1 months for those on standard chemotherapy. Additionally, patients on trastuzumab deruxtecan lived longer overall. These findings suggest that this treatment can be more effective than traditional chemotherapy for this type of breast cancer. Participants in this trial may also be randomized to receive a treatment from the Physician's Choice arm, which includes options like Capecitabine, Eribulin, Gemcitabine, Paclitaxel, or Nab-paclitaxel. ^{3 4 6 7 8}

Who Is on the Research Team?

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Are You a Good Fit for This Trial?

This trial is for adults with HER2-low breast cancer that's inoperable or has spread, and who have tried endocrine therapy without success. They should have had 1-2 prior chemotherapy treatments in the metastatic setting, be able to provide tumor samples, and not have high-HER2 cancer or a history of certain lung conditions.

Inclusion Criteria

I can provide samples of my tumor for testing before treatment starts.

My cancer has grown or spread on my latest scans.

My cancer has low levels of HER2.

Exclusion Criteria

I have been treated with a HER2-targeting therapy before.

I have spinal cord compression or active brain metastases.

My breast cancer has high levels of HER2.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either trastuzumab deruxtecan or physician's choice of chemotherapy

Up to 3 years

Every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Eribulin
• Gemcitabine
• Nab-paclitaxel
• Paclitaxel
• Trastuzumab
• Trastuzumab deruxtecan (DS-8201a)

Trial Overview The study compares DS-8201a (Trastuzumab Deruxtecan) with standard treatments chosen by physicians such as Eribulin, Paclitaxel, Gemcitabine, Capecitabine or Nab-paclitaxel. Participants will receive either the new drug or one of these existing drugs based on their doctor's choice.

How Is the Trial Designed?

Group I: Trastuzumab deruxtecan Experimental Treatment 1 Intervention

HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to DS8201a

Group II: Physician's Choice Active Control 5 Interventions

HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to Physician's choice from the following options: * Capecitabine * Eribulin * Gemcitabine * Paclitaxel * Nab-paclitaxel

Trastuzumab deruxtecan (DS-8201a) is already approved in United States, European Union, Japan for the following indications:

Approved in United States as Enhertu for:

• Unresectable or metastatic HER2-positive breast cancer
• Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma
• Unresectable or metastatic HER2-low breast cancer
• Unresectable or metastatic HER2-positive solid tumors

Approved in European Union as Enhertu for:

• Unresectable or metastatic HER2-positive breast cancer
• Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma

Approved in Japan as Enhertu for:

• Unresectable or metastatic HER2-positive breast cancer
• Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma

Who Is Running the Clinical Trial?

Daiichi Sankyo

Lead 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.

Lead 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

Daiichi Sankyo Co., Ltd.

Industry Sponsor

Trials

116

Recruited

49,200+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

Trastuzumab deruxtecan (ENHERTU®) is an innovative treatment that combines an antibody targeting HER2 with a DNA topoisomerase I inhibitor, specifically designed for HER2-expressing solid tumors, including various types of cancer.

It received accelerated approval in the USA based on the promising results from the phase 2 DESTINY-Breast01 trial, which focused on patients with advanced HER2-positive breast cancer who had already undergone multiple treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: First Approval. Keam, SJ.[2020]

In a phase 2 study involving 184 patients with HER2-positive metastatic breast cancer who had previously been treated with trastuzumab emtansine, trastuzumab deruxtecan demonstrated a significant response rate of 60.9%, with a median response duration of 14.8 months.

While trastuzumab deruxtecan showed promising efficacy, it was associated with notable adverse effects, including interstitial lung disease in 13.6% of patients, highlighting the need for careful monitoring of pulmonary symptoms during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. Modi, S., Saura, C., Yamashita, T., et al.[2021]

In a phase 1 trial involving 115 patients with HER2-positive breast cancer previously treated with trastuzumab emtansine, trastuzumab deruxtecan demonstrated a manageable safety profile, with 59.5% of patients achieving a confirmed objective response.

Despite some serious treatment-emergent adverse events, including cases of interstitial lung disease and pneumonitis, the preliminary efficacy results suggest that trastuzumab deruxtecan is a promising treatment option, warranting further investigation in larger clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Tamura, K., Tsurutani, J., Takahashi, S., et al.[2020]

Fam-trastuzumab deruxtecan-nxki (T-DXd) has been approved for treating HER2-low metastatic breast cancer, showing significant improvements in progression-free survival (PFS) and overall survival (OS) in a phase III trial with 557 patients.

The study demonstrated a 50% reduction in the risk of disease progression and a 36% reduction in the risk of death compared to standard chemotherapy, with a safety profile consistent with previous uses of T-DXd and no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

US Food and Drug Administration Approval Summary: Fam-Trastuzumab Deruxtecan-nxki for Human Epidermal Growth Factor Receptor 2-Low Unresectable or Metastatic Breast Cancer. Narayan, P., Dilawari, A., Osgood, C., et al.[2023]

In a phase 1 trial involving 44 patients with HER2-positive gastric or gastro-oesophageal junction cancer, trastuzumab deruxtecan demonstrated a manageable safety profile, with the most common serious side effects being anemia and decreases in blood cell counts, but no drug-related deaths were reported.

The treatment showed promising preliminary activity, with 43.2% of patients achieving a confirmed objective response, indicating its potential effectiveness in patients who had previously been treated with trastuzumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. Shitara, K., Iwata, H., Takahashi, S., et al.[2020]

Fam-trastuzumab deruxtecan-nxki (ENHERTU) received accelerated FDA approval for treating HER2-positive breast cancer in patients who have already undergone two or more anti-HER2 therapies, based on a study involving 184 patients that showed a confirmed overall response rate of 60.3%.

While ENHERTU is effective, it carries significant risks, including severe interstitial lung disease and neutropenia, highlighting the importance of monitoring for serious side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Fam-Trastuzumab Deruxtecan-Nxki for the Treatment of Unresectable or Metastatic HER2-Positive Breast Cancer. Narayan, P., Osgood, CL., Singh, H., et al.[2022]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2203690

Trastuzumab Deruxtecan in Previously Treated HER2-Low ... In this trial involving patients with HER2-low metastatic breast cancer, trastuzumab deruxtecan resulted in significantly longer progression-free and overall ...

2. nature.com nature.com/articles/s41591-025-03981-4

Trastuzumab deruxtecan in HER2-low metastatic breast ... In DESTINY-Breast04 (NCT03734029), trastuzumab deruxtecan (T-DXd) significantly improved overall survival (OS) and progression-free survival ...

3. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/ENHERTU-fam-trastuzumab-deruxtecan-nxki-reduced-the-risk-of-disease-recurrence-or-death-by-53-percent-vs-T-DM1-in-patients-with-high-risk-HER2-positive-early-breast-cancer-following-neoadjuvant-therapy-in-DESTINY-Breast05-Phase-III-trial.html

ENHERTU® (fam-trastuzumab deruxtecan-nxki) reduced ... More than 92% of patients treated with AstraZeneca and Daiichi Sankyo's ENHERTU were free of invasive disease at three years.

4. enhertu.com enhertu.com/en/her2-low-breast/enhertu-results

ENHERTU® (fam-trastuzumab deruxtecan-nxki) | Results ... ENHERTU helped people live longer without their cancer growing or spreading compared to chemotherapy* †. 13.2 months vs 8.1 months. Median progression-free ...

5. enhertuhcp.com enhertuhcp.com/en/breast/efficacy/efficacy-data

Efficacy data | ENHERTU® (fam-trastuzumab deruxtecan-nxki) Learn about median progression-free survival, overall survival, confirmed objective response rate, tumor response, and NCCN recommendation for patients on ...

6. enhertuhcp.com enhertuhcp.com/en/breast/safety

Safety Data | ENHERTU® (fam-trastuzumab deruxtecan-nxki) The benefit-risk profile of ENHERTU was established in DESTINY-Breast031. The majority of adverse reactions were Grade 1 or 21,2.

7. enhertuhcp.com enhertuhcp.com/en/her2-low-her2-ultralow-breast/safety

Safety data | ENHERTU® (fam-trastuzumab deruxtecan-nxki) The safety of ENHERTU was evaluated in 371 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who received ENHERTU 5.4 mg/ ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11178646/

Safety profile of trastuzumab deruxtecan in advanced breast ... The article covers various aspects of T-DXd treatment, including its clinical efficacy, safety profile, and dosing considerations, and provides practical ...