Trastuzumab Deruxtecan for Advanced Breast Cancer

Not currently recruiting at 289 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Daiichi Sankyo

Must not be taking: Capecitabine

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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 46 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, trastuzumab deruxtecan, for individuals with advanced HER2-positive breast cancer. It focuses on cases where cancer cannot be surgically removed and has metastasized. Researchers aim to compare this treatment to current standard options, such as lapatinib and capecitabine or trastuzumab and capecitabine. Ideal candidates for this trial have previously received standard HER2 therapies and experienced disease progression. As a Phase 3 trial, this study represents the final step before FDA approval, providing patients an opportunity to access 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 coordinators 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 generally well-tolerated by patients with breast cancer. In one study, most patients did not experience serious side effects. Common issues included a drop in white blood cell count and mild nausea. These side effects are typical with many cancer treatments and can usually be managed.

Another study found that over 92% of patients treated with trastuzumab deruxtecan remained free of invasive disease after three years. This suggests the treatment is effective and safe for those with advanced breast cancer.

Prospective clinical trial participants should consult medical professionals to understand how these findings might relate to their health. ^{1 2 3 4 5}

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

Trastuzumab deruxtecan is unique because it combines a targeted therapy approach with a powerful chemotherapy component in one treatment. Unlike standard treatments for HER2-positive advanced breast cancer, such as lapatinib with capecitabine or trastuzumab with capecitabine, trastuzumab deruxtecan uses an innovative antibody-drug conjugate. This design allows it to precisely target and deliver chemotherapy directly to cancer cells, potentially improving effectiveness and reducing harm to healthy cells. Researchers are excited because this dual-action method could lead to better outcomes for patients who have already undergone traditional HER2 therapies.

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

Research has shown that trastuzumab deruxtecan, which participants in this trial may receive, holds promise for treating HER2-positive metastatic breast cancer. In one study, over 92% of patients taking this drug remained free of invasive cancer after three years. It also reduced the risk of cancer recurrence or death by 53% compared to T-DM1. Additionally, trastuzumab deruxtecan demonstrated strong and lasting effects, even in patients with brain metastases. These findings suggest that this treatment could be a powerful option for patients who have already tried other standard treatments. ^{1 4 5 6 7}

Who Is on the Research Team?

Global Team Leader

Principal Investigator

Daiichi Sankyo

Are You a Good Fit for This Trial?

This trial is for adults with HER2-positive breast cancer that's either inoperable or has spread, and who have previously been treated with T-DM1. They must not have participated in certain other drug studies, have no serious heart disease or lung conditions, and agree to use effective contraception.

Inclusion Criteria

I agree to use effective birth control or avoid sex during the study and for months after.

My blood, kidney, and liver functions are all within normal ranges.

I am legally considered an adult in my country.

Exclusion Criteria

I was in a Daiichi Sankyo antibody drug study but my disease didn't worsen within 12 months after.

I have serious heart problems that are not under control.

I have been treated with capecitabine before.

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 (DS-8201a) or investigator's choice treatment (Lapatinib+capecitabine or Trastuzumab+capecitabine)

Up to 46 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Trastuzumab deruxtecan

Trial Overview The study compares a new medication called DS-8201a (Trastuzumab deruxtecan) against standard treatments like Capecitabine, Trastuzumab, and Lapatinib. It aims to see if DS-8201a is more effective for those who've had prior treatment.

How Is the Trial Designed?

Group I: Trastuzumab deruxtecan (DS-8201a) Experimental Treatment 1 Intervention

HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), randomized to treatment with DS-8201a

Group II: Lapatinib+capecitabine Active Control 2 Interventions

HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), randomized to investigator's choice treatment with Lapatinib/capecitabine

Group III: Trastuzumab+capecitabine Active Control 2 Interventions

HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), randomized to investigator's choice treatment with Trastuzumab/capecitabine

Trastuzumab deruxtecan 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 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 is an effective treatment for advanced HER2-positive breast cancer, showing a response rate of 60.9% in major clinical trials, making it a viable option for patients who have not responded to standard therapies.

While the drug is effective, it comes with potential side effects, including serious risks like interstitial lung disease and left ventricular dysfunction, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Fam-Trastuzumab Deruxtecan-nxki in HER2-Positive Breast Cancer. Nguyen, X., Hooper, M., Borlagdan, JP., et al.[2021]

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]

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]

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]

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]

In the DESTINY-Breast03 trial, trastuzumab deruxtecan (T-DXd) demonstrated superior progression-free survival and overall survival compared to trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer, while maintaining quality of life (QoL) throughout treatment.

Patients receiving T-DXd experienced a median time to first hospitalization that was three times longer than those on T-DM1, indicating better overall health management and fewer hospital visits during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study. Curigliano, G., Dunton, K., Rosenlund, M., et al.[2023]

Citations

1. 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.

2. 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 ...

3. nature.com nature.com/articles/s41591-024-03261-7

Trastuzumab deruxtecan in HER2-positive advanced ... These data show substantial and durable overall and intracranial activity for T-DXd, supporting its use in previously treated patients with HER2 + mBC.

4. 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 ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39662227/

Use and outcomes of trastuzumab deruxtecan in HER2- ... In this large French observational study, T-DXd users were older, had more comorbidities, and had more brain metastases than patients included in registration ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40947843/

Real-world safety and efficacy of trastuzumab deruxtecan ... Our study confirms the efficacy and safety of T-DXd in daily clinical practice. Further research and longer patient follow-up are needed to ...

7. ascopost.com ascopost.com/news/october-2025/her2-positive-early-breast-cancer-trastuzumab-deruxtecan-moves-into-earlier-clinical-settings/

HER2-Positive Early Breast Cancer: Trastuzumab ... In DESTINY-Breast05, treatment with T-DXd yielded nearly a 9% absolute improvement in 3-year invasive disease–free survival over T-DM1, ...