Trastuzumab Deruxtecan for Breast Cancer

Recruiting at 97 trial locations

Overseen By (Asia Sites) Daiichi Sankyo Contact for Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Daiichi Sankyo

Must not be taking: Antibody drug conjugates

Disqualifiers: Cardiovascular disease, ILD, CNS metastases, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called trastuzumab deruxtecan (also known as Enhertu or DS-8201a) for individuals with certain types of advanced breast cancer. It aims to assess the safety and effectiveness of this treatment for breast cancer that cannot be surgically removed or has metastasized. The trial seeks participants with low levels of the HER2 protein who have already tried one or two other treatments. Participants should have breast cancer that either does not respond to hormone therapy or meets specific conditions related to hormone receptor status and treatment history. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants the opportunity to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that there should be an adequate treatment washout period before enrollment, which might mean you need to stop certain medications for a time before starting the trial.

Is there any evidence suggesting that trastuzumab deruxtecan is likely to be safe for humans?

Research has shown that trastuzumab deruxtecan, also known as Enhertu, holds promise for treating certain types of breast cancer. In one study, over 92% of patients who received this drug remained free of invasive disease after three years, indicating that the treatment is generally well-tolerated over time.

Another study found that trastuzumab deruxtecan significantly reduced the risk of disease progression compared to traditional chemotherapy, suggesting it might be a safer option for some patients.

Additionally, the FDA has approved trastuzumab deruxtecan for treating breast cancer that cannot be surgically removed or has metastasized, specifically HR-positive, HER2-low breast cancer. This approval confirms the drug has met safety standards for these conditions.

Overall, while all treatments carry some risks, research suggests that trastuzumab deruxtecan is generally well-tolerated and may offer benefits for individuals with specific types of breast cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Trastuzumab Deruxtecan is unique because it combines an antibody with a potent chemotherapy drug, creating a targeted therapy for breast cancer. Unlike traditional treatments that may affect healthy cells, this drug specifically targets cancer cells with HER2-low or HER2 IHC 0 expressions, which are not typically addressed by existing HER2-targeted therapies. Researchers are excited because this approach could lead to more effective treatments with potentially fewer side effects, offering hope to patients with limited options in the metastatic setting.

What evidence suggests that trastuzumab deruxtecan could be an effective treatment for breast cancer?

Research has shown that trastuzumab deruxtecan (T-DXd) effectively treats various types of advanced breast cancer. In this trial, participants will be divided into cohorts based on their cancer characteristics. Studies have found that T-DXd benefits patients with both hormone receptor (HR)-positive and HR-negative HER2-low breast cancer. It significantly improved survival rates and slowed disease progression compared to other treatments. Specifically, for HR-positive HER2-low cancer, T-DXd reduced the risk of disease progression by about 50%. In HR-negative HER2-low cases, it also extended patient survival. These findings suggest that T-DXd could be a promising option for those with difficult-to-treat breast cancer types. ^{1 2 5 6 7}

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 unresectable/metastatic breast cancer that's either hormone receptor-negative or -positive but HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2 IHC 0. Participants must not have been previously treated with anti-HER2 therapy in the metastatic setting and should have had one to two prior lines of therapy for their metastatic disease.

Inclusion Criteria

My cancer returned within 2 years after starting hormone therapy, or it got worse within 12 months after or during a specific treatment.

My cancer is confirmed as HER2-low or HER2-negative.

My cancer may or may not respond to hormones.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Trastuzumab Deruxtecan (T-DXd) for the treatment of unresectable and/or metastatic HER2-low or HER2 IHC 0 breast cancer

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Trastuzumab Deruxtecan

Trial Overview The study tests Trastuzumab Deruxtecan (T-DXd) on patients with specific types of breast cancer. It aims to assess how safe and effective T-DXd is in treating those whose tumors are low in a protein called HER2, which can affect cancer growth.

How Is the Trial Designed?

Group I: Cohort 4: HR-positive, HER2 IHC 0 Experimental Treatment 1 Intervention

Participants with HR-positive HER2 IHC 0 unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd.

Group II: Cohort 3: HR-positive, HER2-low Experimental Treatment 1 Intervention

Participants with HR-positive HER2-low unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd. Participants must also have recurrent disease \<2 years from the initiation of adjuvant ET or have disease progression on CDK4/6 inhibitor-based regimen within 12 months of completion of adjuvant therapy with a CDK4/6 inhibitor or have disease progression within the first 12 months of CDK4/6 in the first line metastatic setting.

Group III: Cohort 2: HR-negative, HER2 IHC 0 Experimental Treatment 1 Intervention

Participants with HR-negative HER2 IHC 0 unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd.

Group IV: Cohort 1: HR-negative, HER2-low Experimental Treatment 1 Intervention

Participants with HR-negative HER2-low unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd.

Trastuzumab Deruxtecan is already approved in European Union, United States, Japan for the following indications:

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 United States as Enhertu for:

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

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

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

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]

Trastuzumab deruxtecan (Enhertu®) has been shown to significantly improve progression-free survival in adults with unresectable or metastatic HER2-positive breast cancer compared to the previous standard treatment, trastuzumab emtansine, in a pivotal phase 3 trial.

The treatment has a generally manageable safety profile, although it is associated with common adverse events like hematological and gastrointestinal disorders, and requires careful monitoring for interstitial lung disease (ILD)/pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Unresectable or Metastatic HER2-Positive Breast Cancer. Nie, T., Blair, HA.[2023]

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]

Trastuzumab deruxtecan (DS-8201a) is an innovative antibody-drug conjugate that combines a monoclonal anti-HER2 antibody with a cytotoxic agent, showing promising results in heavily pretreated HER2-positive breast cancer patients, with a 60% overall response rate and 97% disease control reported in a phase 2 trial.

The FDA has granted accelerated approval for DS-8201a for advanced or unresectable HER2-positive breast cancer after at least two prior HER2-targeting treatments, highlighting its potential as a new treatment option for patients with limited alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan (DS-8201a): The Latest Research and Advances in Breast Cancer. Andrikopoulou, A., Zografos, E., Liontos, M., 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]

Trastuzumab deruxtecan (Enhertu®) has been shown to be significantly more effective than standard chemotherapy in improving overall survival and achieving objective responses in adults with advanced HER2-positive gastric or gastro-oesophageal junction adenocarcinoma, based on results from the phase II DESTINY-Gastric01 trial.

The treatment is generally well-tolerated, with common side effects including nausea and fatigue, but it does carry important safety warnings for interstitial lung disease and embryo-foetal toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Gastric or Gastro-Oesophageal Junction Adenocarcinoma. Kang, C.[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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12479221/

Efficacy of Trastuzumab Deruxtecan in HER2-Positive and ... Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan ...

2. 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.

3. 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 ...

4. 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 ...

5. esmoopen.com esmoopen.com/article/S2059-7029(25)01199-8/fulltext

Outcomes with trastuzumab deruxtecan by biomarker ... In a large (n = 1490) real-world dataset, T-DXd exhibited favorable activity for metastatic breast cancer (MBC).

6. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2025/enhertu-approved-in-us-for-breast-cancer-post-et.html

Enhertu approved in the US as first HER2-directed therapy ... In the trial, Enhertu showed a 36% reduction in the risk of disease progression or death versus chemotherapy (hazard ratio [HR] 0.64; 95% ...

7. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-fam-trastuzumab-deruxtecan-nxki-unresectable-or-metastatic-hr-positive-her2-low-or-her2

FDA approves fam-trastuzumab deruxtecan-nxki for breast ... FDA approves fam-trastuzumab deruxtecan-nxki for unresectable or metastatic HR-positive, HER2-low or HER2-ultralow breast cancer.