Trastuzumab Deruxtecan for Breast Cancer

(DB-06 Trial)

Recruiting at 252 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

866 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Trastuzumab Deruxtecan for breast cancer?

Trastuzumab Deruxtecan has shown effectiveness in treating HER2-positive breast cancer, especially in patients who have already tried other treatments. In clinical trials, it improved the time patients lived without the cancer getting worse and had a high response rate, meaning many patients saw their cancer shrink or stop growing. ^{1 2 3 4 5}

Is Trastuzumab Deruxtecan safe for humans?

Trastuzumab Deruxtecan has been shown to have a generally manageable safety profile in clinical trials for breast and gastric cancers. Common side effects include blood and stomach-related issues, and there is a warning for lung problems, which require careful monitoring. ^{1 3 4 6 7}

What makes the drug Trastuzumab Deruxtecan unique for treating HER2-positive breast cancer?

Trastuzumab Deruxtecan is unique because it combines a HER2-targeted antibody with a powerful cancer-killing agent, offering a new option for patients with HER2-positive breast cancer who have already tried other treatments. It has shown effectiveness in prolonging the time patients live without their cancer worsening, compared to previous treatments. ^{1 2 3 4 7}

What is the purpose of this trial?

This trial is testing a new drug called trastuzumab deruxtecan for patients with advanced breast cancer that hasn't responded to other treatments. The drug works by specifically targeting and killing cancer cells. The study aims to see if this drug helps patients live longer or improves their quality of life compared to other treatments. Trastuzumab deruxtecan has shown significant clinical benefits in treating advanced breast cancer and other similar tumors.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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®) 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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Unresectable or Metastatic HER2-Positive Breast Cancer. [2023]

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

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: First Approval. [2020]

4. England 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. [2020]

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

Trastuzumab Deruxtecan (DS-8201a): The Latest Research and Advances in Breast Cancer. [2021]

6. France pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Gastric or Gastro-Oesophageal Junction Adenocarcinoma. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. [2020]