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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new treatment, trastuzumab deruxtecan (Enhertu), alone or with anastrozole (Arimidex), for a specific type of breast cancer. It targets those with hormone receptor-positive breast cancer (where cancer cells grow in response to hormones) and low levels of the HER2 protein. The goal is to determine if these drugs can effectively target and kill cancer cells. Suitable participants have a breast tumor larger than 2 cm, reside in the U.S., and have not received prior treatment for their cancer. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found trastuzumab deruxtecan to be safe for patients with breast cancer. Research shows that about 65% of patients experienced a drop in neutrophil count, a type of white blood cell that helps fight infections. However, these side effects were generally manageable and usually not severe.

When combined with anastrozole, studies showed promising results. Anastrozole lowers estrogen levels, which can help slow the growth of some breast cancers. The combination proved effective and showed good results in early treatments of breast cancer with low HER2 levels.

Overall, existing studies suggest that trastuzumab deruxtecan, whether used alone or with anastrozole, is well-tolerated. As further testing continues, researchers closely monitor any side effects to ensure patient safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Trastuzumab Deruxtecan and Anastrozole for breast cancer because they offer a novel approach compared to traditional treatments like surgery, chemotherapy, and hormone therapy. Trastuzumab Deruxtecan is an antibody-drug conjugate that directly delivers chemotherapy to cancer cells, potentially increasing its effectiveness while minimizing damage to healthy cells. Anastrozole, a well-known aromatase inhibitor, reduces estrogen levels, which can help slow the growth of hormone-receptor-positive breast cancer. Combining these two treatments could provide a powerful one-two punch, improving outcomes for patients with specific types of breast cancer.

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

Research has shown that the drug trastuzumab deruxtecan can lower the risk of death by 31% in patients with HER2-low breast cancer. In this trial, some participants will receive trastuzumab deruxtecan alone, while others will receive it with anastrozole, a medication that reduces estrogen levels. This combination has shown promising results in fighting tumors in these patients. It is especially effective for those who have not yet received chemotherapy and offers hope for patients with HER2-low, hormone receptor-positive breast cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Nicholas P McAndrew, M.D.

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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-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 (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 (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]

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]

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 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) Median time to first onset was 5.5 months (range: 0.9 to 31.5). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.9% of patients treated with ENHERTU.

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. sciencedirect.com sciencedirect.com/science/article/pii/S2949820124000730

Real-world safety and effectiveness data of trastuzumab ... Real-world safety and effectiveness data of trastuzumab deruxtecan and sacituzumab govitecan in breast cancer: a Hellenic Cooperative Oncology Group study.

7. 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) ...

8. enhertuhcp.com enhertuhcp.com/en/breast/safety

Safety 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.

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.