Trastuzumab Deruxtecan for Advanced HER2 Positive Cancer

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

63 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the biological effects of DS-8201a on patients with HER2 positive cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). DS-8201a works by binding to a protein called HER2 that is present on the surface of tumor cells. This allows DS-8201a to kill the tumor cells by damaging their deoxyribonucleic acid (DNA), resulting in tumor cell death. This study looks at how DS-8201a may affect the levels of certain proteins and immune cells in tumors and how well the drug works against tumor cells by examining cells from a small piece tumor taken before and after DS-8201a is given.

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.

What data supports the effectiveness of the drug Trastuzumab Deruxtecan for advanced HER2-positive cancer?

Trastuzumab Deruxtecan has shown effectiveness in treating HER2-positive breast cancer, with studies indicating it prolongs progression-free survival compared to other treatments. It has also been effective in HER2-positive gastric cancer, improving overall survival and response rates compared to standard chemotherapy. ^{1 2 3 4 5}

Is Trastuzumab Deruxtecan 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 and gastric cancers. Common side effects include blood and stomach issues, and there is a warning for lung problems, which require careful monitoring. ^{1 2 3 5 6}

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

Trastuzumab Deruxtecan is unique because it combines a HER2-targeted antibody with a powerful cancer-killing agent, topoisomerase I inhibitor, allowing it to specifically target and destroy cancer cells. It has shown effectiveness in patients who have already tried other HER2-targeted treatments, offering a new option for those with advanced HER2-positive cancers. ^{1 2 3 4 6}

Research Team

Sarah Shin

Principal Investigator

National Cancer Institute LAO

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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

Trastuzumab Deruxtecan: First Approval. [2020]

2. France pubmed.ncbi.nlm.nih.gov

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

3. 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]

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

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

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

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

6. 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]