Trastuzumab Deruxtecan for Advanced HER2 Positive Cancer

Not currently recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Chloroquine, Hydroxychloroquine

Disqualifiers: Pulmonary illnesses, Recent chemotherapy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Up to disease progression or unacceptable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests trastuzumab deruxtecan for individuals with advanced HER2-positive cancer, a type that has spread and does not respond to standard treatments. The goal is to determine how effectively this drug targets and kills tumor cells by binding to the HER2 protein on those cells. Participants may qualify if they have HER2-positive cancer that has spread and is unresponsive to other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that patients cannot receive chloroquine/hydroxychloroquine and require a washout period of more than 14 days if they have been taking it. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that Trastuzumab Deruxtecan is likely to be safe for humans?

Research shows that trastuzumab deruxtecan, also known as DS-8201a, may effectively treat advanced HER2-positive cancer. In earlier studies, this treatment proved particularly effective for patients who had already tried other cancer therapies. However, safety remains a concern with new treatments.

Studies report common side effects, including nausea and a drop in white blood cell count, affecting over 60% of patients. White blood cells are crucial for fighting infections. Despite these side effects, most patients can continue treatment without interruption.

In some cases, patients had to stop taking the drug due to side effects, but this was uncommon. Anyone considering joining a clinical trial should discuss the potential risks and benefits with their doctor to ensure the best decision for their health. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for HER2-positive cancer, which typically involve a combination of chemotherapy and targeted therapies like trastuzumab, trastuzumab deruxtecan offers a novel approach by combining a HER2-targeted antibody with a potent chemotherapy drug. This combination allows for a more precise delivery of the chemotherapy directly to the cancer cells, potentially minimizing damage to healthy cells and enhancing effectiveness. Researchers are excited about trastuzumab deruxtecan because it has a unique mechanism of action that not only targets cancer cells more accurately but also has shown promising results in overcoming resistance seen with existing treatments.

What evidence suggests that Trastuzumab Deruxtecan might be an effective treatment for advanced HER2 positive cancer?

Research has shown that trastuzumab deruxtecan, which participants in this trial will receive, holds promise for treating HER2-positive cancers. In one study, over 92% of patients who received this drug had no invasive disease after three years. The treatment also demonstrated lasting effects in patients with previously treated HER2-positive metastatic breast cancer. Another study found that many patients experienced no cancer progression, with an average of 17.3 months before the cancer worsened. These results suggest that trastuzumab deruxtecan may effectively slow or stop the spread of HER2-positive cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Sarah Shin

Principal Investigator

National Cancer Institute LAO

Are You a Good Fit for This Trial?

This trial is for adults with advanced HER2 positive cancer, who have measurable or evaluable disease and are not responding to standard treatments. Participants must be willing to undergo biopsies, provide blood samples, and have a good performance status (able to carry out daily activities). They should not be pregnant or breastfeeding and must use contraception. People with recent major surgeries, certain heart conditions, uncontrolled infections or illnesses that could interfere with the study cannot join.

Inclusion Criteria

I haven't had any blood or platelet transfusions in the last week.

Patients must have measurable or evaluable disease

I had hepatitis C but have been treated and cured.

Exclusion Criteria

I still have side effects from past cancer treatments.

I have undergone radiation therapy recently.

I had major surgery less than 4 weeks ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive trastuzumab deruxtecan intravenously every 21 days in 21-day cycles

Up to disease progression or unacceptable toxicity

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

40 days

What Are the Treatments Tested in This Trial?

Interventions

• Biopsy
• Biospecimen Collection
• Trastuzumab Deruxtecan

Trial Overview The trial is testing DS-8201a's biological effects on patients with advanced HER2 positive cancers. It involves examining how this drug affects protein levels and immune cells in tumors by analyzing biopsy samples before and after treatment. The study includes tests like echocardiography, MRI scans, CT scans, MUGA scans, biospecimen collection, and biopsies to monitor the drug's impact.

How Is the Trial Designed?

Group I: Treatment (trastuzumab deruxtecan) Experimental Treatment 7 Interventions

Patients receive trastuzumab deruxtecan IV over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA, CT or MRI, biopsies, and collection of blood samples throughout the study.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

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]

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]

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 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 (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]

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

Efficacy of Trastuzumab Deruxtecan in HER2-Positive and ... HER2-positive patients experienced longer PFS compared to HER2-low patients (not reached vs 9.0 months). Among HER2-low patients, liver ...

3. esmoopen.com esmoopen.com/article/S2059-7029(25)01380-8/fulltext

Effectiveness of post-trastuzumab deruxtecan treatments ... We found that median post-T-DXd rwPFS was 4.1 months and the median OS was 16.2 months, 73.2% of patients received a different anti-HER2 therapy ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1914510

Trastuzumab Deruxtecan in Previously Treated HER2- ... Trastuzumab deruxtecan showed durable antitumor activity in a pretreated patient population with HER2-positive metastatic breast cancer.

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

Trastuzumab deruxtecan in HER2-positive advanced ... Overall, 89 patients (33.8%) were free of progression at the time of the analysis, and median PFS (post hoc analysis) was 17.3 months (95% CI: ...

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

Safety profile of trastuzumab deruxtecan in advanced breast ... T-DXd represents a highly efficacious treatment option for pretreated patients with HER2-positive and HER2-low advanced or metastatic breast cancer. Results ...

7. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/ENHERTU-fam-trastuzumab-deruxtecan-nxki-followed-by-THP-before-surgery-resulted-in-a-pathologic-complete-response-in-67-percent-of-patients-with-high-risk-HER2-positive-early-stage-breast-cancer-in-DESTINY-Breast11-Phase-III-trial.html

ENHERTU® (fam-trastuzumab deruxtecan-nxki) followed ... The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (61%), decreased white blood cell count (60%), ...

8. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/enhertu

Enhertu | European Medicines Agency (EMA) The tumour shrank in around 61% of the 184 patients treated with the recommended dose of Enhertu. A second main study involved 524 patients previously treated ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e12518

Real-world safety and discontinuation rates of fam- ... Our study evaluates real-world adverse event rates causing treatment discontinuation, to assess Enhertu's safety in patients with advanced metastatic cancer.