Trastuzumab Deruxtecan + Anastrozole for Breast Cancer

Recruiting at 6 trial locations

Overseen By TRIO-US

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Must be taking: Ovarian suppression drugs

Must not be taking: Aromatase inhibitors

Disqualifiers: Recurrent cancer, Metastatic cancer, others

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

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

Compensation: Varies

Number of Visits: 7

Duration: 18 weeks

88 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, there is a required washout period for certain treatments, like major surgery and chloroquine/hydroxychloroquine, before joining the trial.

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

Trastuzumab Deruxtecan has shown effectiveness in treating HER2-positive breast cancer, with studies indicating prolonged progression-free survival and a generally manageable safety profile. It has been approved for use in patients who have previously received other anti-HER2 treatments. ^{1 2 3 4 5}

Is Trastuzumab Deruxtecan + Anastrozole safe for humans?

Trastuzumab deruxtecan, also known as Enhertu or DS-8201a, has been shown to have a generally manageable safety profile in clinical trials for HER2-positive breast cancer. Common side effects include nausea, fatigue, and hair loss, with some risk of lung-related issues like interstitial lung disease or pneumonitis, which require careful monitoring. ^{1 2 4 6 7}

How is the drug Trastuzumab Deruxtecan + Anastrozole unique for breast cancer treatment?

Trastuzumab Deruxtecan is a novel drug that combines a HER2-targeted antibody with a powerful cancer-killing agent, making it effective for patients with HER2-positive breast cancer who have already tried other treatments. It is unique because it targets cancer cells more precisely, potentially leading to better outcomes for those with advanced or metastatic breast cancer. ^{1 2 3 4 8}

What is the purpose of this trial?

This phase II trial investigates how well trastuzumab deruxtecan works alone or in combination with anastrozole in treating patients with HER2 low, hormone receptor positive breast cancer. Trastuzumab deruxtecan is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug called deruxtecan. Trastuzumab attaches to HER2 expressed at low levels on cancer cells in a targeted way and delivers deruxtecan to kill them. Anastrozole works by decreasing estrogen production and suppressing the growth of tumors that need estrogen to grow. This study is evaluating how effective trastuzumab deruxtecan is at treating hormone receptor positive cancer cells that have low levels of HER2 expressed on them when given alone or in combination with anastrozole.

Research Team

Nicholas P McAndrew, M.D.

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

This trial is for postmenopausal women or those willing to undergo ovarian suppression, with early-stage HER2 low, hormone receptor-positive breast cancer. They should have good physical function and no severe medical conditions that could interfere with the study. Participants must not have had certain prior treatments or conditions like active infections, recent heart issues, or a history of severe allergies to similar drugs.

Inclusion Criteria

I haven't had major surgery in the last 4 weeks or taken Chloroquine/hydroxychloroquine in the last 14 days.

In the United States

My tumor is hormone receptor positive for estrogen and progesterone.

Exclusion Criteria

I have had treatment that goes through my whole body for cancer.

In the past year, I've had a serious heart condition like a sudden stop in heartbeat or abnormal heart rhythm.

I have had a stem-cell transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive trastuzumab deruxtecan with or without anastrozole for up to 6 cycles, each cycle lasting 21 days, followed by surgery

18 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

3-4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Anastrozole
• Therapeutic Conventional Surgery
• Trastuzumab Deruxtecan

Trial Overview The effectiveness of Trastuzumab Deruxtecan alone or combined with Anastrozole is being tested in patients with specific breast cancer types. Trastuzumab Deruxtecan targets and delivers chemotherapy directly to cancer cells while Anastrozole suppresses tumor growth by reducing estrogen production.

Participant Groups

Group I: Arm B (trastuzumab deruxtecan, anastrozole) Experimental Treatment 3 Interventions

Patients receive trastuzumab deruxtecan IV over 90 minutes on cycle 1 day 1 and 30 minutes on day 1 of each subsequent cycle and anastrozole PO QD on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery.

Group II: Arm A (trastuzumab deruxtecan) Active Control 2 Interventions

Patients receive trastuzumab deruxtecan IV over 90 minutes on cycle 1 day 1 and 30 minutes on day 1 of each subsequent cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery.

Anastrozole is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Arimidex for:

• Breast cancer
• Early breast cancer in postmenopausal women

Approved in United States as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer

Approved in Canada as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• Treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Approved in Japan as Arimidex for:

• Breast cancer

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Translational Research in Oncology-U.S

Collaborator

Trials

2

Recruited

160+

Daiichi Sankyo Co., Ltd.

Industry Sponsor

Trials

116

Recruited

49,200+

Findings from Research

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]

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®) 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]

Trastuzumab deruxtecan (DS-8201) shows promising efficacy in treating HER2-low/positive advanced breast cancer, with an overall response rate of 57% and a disease control rate of 92% across 10 studies involving 1,108 patients.

The treatment is generally safe, with common side effects including nausea (62%), fatigue (44%), and a 13% incidence of drug-related interstitial lung disease, but only 1% of patients experienced severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of trastuzumab deruxtecan in the treatment of HER2-low/positive advanced breast cancer: a single-arm meta-analysis. Li, Z., Guo, S., Xue, H., et al.[2023]

Trastuzumab deruxtecan (T-DXd) was evaluated for safety in 1457 patients across 8 clinical trials, revealing that gastrointestinal disorders and blood-related issues were the most common adverse events, with neutropenia being the most severe (21.4% incidence).

The study highlighted significant concerns regarding interstitial lung disease (10.9% incidence) and decreased left ventricular ejection fraction (1.2% incidence), suggesting that while T-DXd is generally well tolerated, these specific side effects require careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of trastuzumab deruxtecan: A meta-analysis and pharmacovigilance study. Guo, Z., Ding, Y., Wang, M., 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]

References

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

Trastuzumab Deruxtecan: First Approval. [2020]

2. 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]

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

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

4. France pubmed.ncbi.nlm.nih.gov

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

5. France pubmed.ncbi.nlm.nih.gov

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of trastuzumab deruxtecan in the treatment of HER2-low/positive advanced breast cancer: a single-arm meta-analysis. [2023]

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

Safety of trastuzumab deruxtecan: A meta-analysis and pharmacovigilance study. [2023]

8. 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]