Trastuzumab Deruxtecan for Breast Cancer

(DB-06 Trial)

Not currently recruiting at 307 trial locations

Overseen By AZ Breast Cancer Study Navigators

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Endocrine therapy

Disqualifiers: Lung disease, Cardiovascular, 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: 16

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of trastuzumab deruxtecan (Enhertu) compared to standard chemotherapy for certain breast cancer patients. It targets those with advanced or metastatic cancer and a specific type called HER2-low, hormone receptor-positive. Suitable candidates have experienced disease progression despite hormone treatments combined with other therapies. The trial aims to determine if trastuzumab deruxtecan can better control cancer growth and assess its safety. As a Phase 3 trial, it represents the final step before FDA approval, providing patients access to 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. However, since the study involves comparing a new treatment with chemotherapy, it's possible that changes to your medication regimen might be required. Please consult with the trial coordinators for specific guidance.

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 earlier studies, about 92% of patients who took this drug did not experience cancer recurrence after three years. However, some individuals experienced side effects. Approximately 7.1% of patients discontinued treatment due to these issues, and around 13% developed a lung condition that can cause scarring. These studies suggest that while the treatment can be effective, it carries some risks that should be considered. ^{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 chemotherapy drug, creating a powerful duo that targets cancer cells more precisely. Unlike standard chemotherapies like capecitabine or paclitaxel, which affect both healthy and cancerous cells, trastuzumab deruxtecan specifically seeks out and attaches to HER2 proteins found on certain breast cancer cells. This targeted approach not only aims to improve effectiveness but also reduces damage to healthy cells, potentially leading to fewer side effects. Researchers are excited about this treatment due to its innovative mechanism that promises a more effective and safer option for patients battling HER2-positive breast cancer.

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

Research has shown that trastuzumab deruxtecan, which participants in this trial may receive, holds promise for treating breast cancer. One study found that patients with HER2-low, hormone receptor-positive breast cancer had a 31% lower risk of death when treated with this drug. Another study reported that these patients experienced about 15 months without cancer progression. Additionally, 48% of patients saw a reduction in tumor size. These findings suggest that trastuzumab deruxtecan could be an effective option for individuals with this type of breast cancer. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced or metastatic breast cancer that has low HER2 expression and progressed after endocrine therapy. Participants must not have had prior chemotherapy for their advanced cancer, should have adequate organ function, and provide tumor samples to confirm HER2 status. Those with significant lung disease, uncontrolled heart conditions, active infections, or a history of certain lung problems are excluded.

Inclusion Criteria

I haven't had chemotherapy for advanced breast cancer.

My organs and bone marrow are functioning well.

My breast cancer is advanced or has spread, and tests show specific HER2 levels.

Exclusion Criteria

I do not have serious heart disease or infections.

Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study during the follow up period of a prior interventional study (prescreening for this study while a patient is on treatment in another clinical study is acceptable)

I have spinal cord compression or active brain metastases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either trastuzumab deruxtecan or investigator's choice chemotherapy

48 weeks

Every 6 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 43.85 months

Every 9 weeks (in-person)

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Nab-Paclitaxel
• Paclitaxel
• Trastuzumab Deruxtecan

Trial Overview The study compares the effectiveness of Trastuzumab Deruxtecan (T-DXd) against standard chemotherapies like Capecitabine and Paclitaxel in patients with specific types of breast cancer. It aims to see which treatment is better at controlling the disease while monitoring safety and tolerability.

How Is the Trial Designed?

Group I: Trastuzumab deruxtecan Experimental Treatment 1 Intervention

Trastuzumab deruxtecan (T-DXd; DS-8201a) arm

Group II: Standard of Care Active Control 3 Interventions

Investigator's choice standard of care chemotherapy (capecitabine, paclitaxel, nab-paclitaxel) arm

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?

AstraZeneca

Lead 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

Daiichi Sankyo Company, Limited 3-5-1 Nihonbashihoncho, Chuo-ku, Tokyo

Collaborator

Trials

3

Recruited

1,900+

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

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 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]

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 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®) 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 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]

Citations

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

Efficacy of Trastuzumab Deruxtecan in HER2-Positive and ... Among the 98 patients, the median PFS was 15.0 months. The ORR, DCR, and CBR were 48.0%, 69.4%, and 41.8%, respectively. HER2-positive patients ...

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

Efficacy data | ENHERTU® (fam-trastuzumab deruxtecan-nxki) In patients with metastatic breast cancer and other solid tumors treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients.

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

Trastuzumab deruxtecan in HER2-low metastatic breast ... Patients treated with T-DXd had a 31% reduction in the risk of death in both the overall and HR+ cohorts and a 42% reduction in risk of death in ...

4. 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).

5. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/ENHERTU-fam-trastuzumab-deruxtecan-nxki-demonstrated-highly-statistically-significant-and-clinically-meaningful-improvement-in-invasive-disease-free-survival-vs-T-DM1-in-DESTINY-Breast05-Phase-III-trial-in-patients-with-high-risk-early-breast-cancer-following-neoadjuvant-therapy.html

ENHERTU® (fam-trastuzumab deruxtecan-nxki) ... ENHERTU® (fam-trastuzumab deruxtecan-nxki) demonstrated highly statistically significant and clinically meaningful improvement in invasive ...

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

Safety profile of trastuzumab deruxtecan in advanced breast ... The percentage of patients with a confirmed objective response among all patients was 52.3% (95% CI 47.1–57.4) in the T-DXd arm and 16.3% (95% CI: 11.3 to 22.5) ...

7. 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.

8. esmoopen.com esmoopen.com/article/S2059-7029(25)01716-8/fulltext

Real-world safety and efficacy profiles of trastuzumab ... Trastuzumab deruxtecan (T-DXd) is associated with a significant rate of discontinuation (∼7.1%) and ILD (∼13%). •. Safety and efficacy profiles ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e13023

Efficacy and safety of trastuzumab deruxtecan in HER2+ ... Our study supports the efficacy and safety of T-DXd in India in a real-world clinical setting with results being consistent across published literature.

10. 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 ...