Trastuzumab Deruxtecan for Cancer

(DPT01 Trial)

Recruiting at 34 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Disqualifiers: Her2+ breast cancer, Her2+ gastric cancer, Her2+ gastroesophageal cancer, Her2 mutant NSCLC, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: Approximately 24 months

102 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests trastuzumab deruxtecan, a targeted cancer therapy, to evaluate its effectiveness for individuals with certain advanced solid tumors that cannot be surgically removed or have metastasized. It targets those with specific HER2 gene mutations who have exhausted other treatments or lack viable options. Participants who have previously received HER2-targeted therapy are eligible. For individuals with a solid tumor featuring a specific HER2 mutation and limited treatment options, this trial may be suitable. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering hope for those seeking new options.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, prior HER2 targeting therapy is allowed, so you may be able to continue some treatments. 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, a cancer treatment, has undergone safety studies. In previous studies with patients who have advanced breast cancer and other solid tumors, many experienced a drop in their neutrophil count. Neutrophils, a type of white blood cell, help fight infections. About 65% of patients experienced this drop.

Warnings exist about the risk of lung problems and potential harm to unborn babies, which are serious concerns. Other common side effects, reported by 73% of patients, include a decrease in white blood cell count.

These findings are important because they highlight the treatment's possible side effects and risks. However, the treatment is already approved for other conditions, indicating it is considered safe for some uses. Patients should always consult a doctor to determine if this treatment is appropriate. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Trastuzumab deruxtecan is unique because it combines a targeted therapy with a chemotherapy agent in one powerful package. Unlike other treatments for cancer, which may involve separate drugs for targeting and killing cancer cells, this drug links trastuzumab, a monoclonal antibody that specifically targets the HER2 protein on cancer cells, with deruxtecan, a chemotherapy agent. This targeted approach means it can deliver the chemotherapy directly to the cancer cells with greater precision, potentially enhancing effectiveness and minimizing damage to healthy cells. Researchers are excited because this could lead to better outcomes with fewer side effects compared to traditional chemotherapy regimens.

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

Research has shown that trastuzumab deruxtecan, also known as ENHERTU®, yields promising results in treating certain cancers. In studies involving patients with HER2-positive breast cancer, over 92% remained free of invasive disease after three years. This treatment reduced the risk of cancer recurrence or progression by 53% compared to another common treatment, T-DM1. Participants in this trial will receive trastuzumab deruxtecan, which targets specific changes, called HER2 mutations, in cancer cells. This targeted approach may prove effective for different solid tumors with similar mutations, even if other treatments have failed. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced solid tumors that have specific HER2 mutations and have worsened after previous treatments or lack other options. Participants must be able to provide a tumor sample, have a heart function of at least 50%, and be relatively fit (ECOG 0-1).

Inclusion Criteria

LVEF ≥50%

I have previously received treatment targeting HER2.

I am fully active or can carry out light work.

Exclusion Criteria

I do not have an infection needing IV treatment.

My lung cancer is caused by a HER2 mutation.

My cancer is HER2 positive.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive T-DXd monotherapy for the treatment of unresectable and/or metastatic solid tumors harboring HER2 activating mutations

Approximately 24 months

Tumor scans every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Trastuzumab deruxtecan

Trial Overview The study tests Trastuzumab deruxtecan (T-DXd) in patients with unresectable/metastatic solid tumors harboring HER2 mutations. It's an open-label, single-arm Phase II trial allowing prior HER2 therapy.

How Is the Trial Designed?

Group I: T-DXd Experimental Treatment 1 Intervention

T-DXd monotherapy

Trastuzumab deruxtecan is already approved in United States, European Union, Japan for the following indications:

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
• Unresectable or metastatic HER2-low breast cancer
• Unresectable or metastatic HER2-positive solid tumors

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 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 Co., Ltd.

Industry Sponsor

Trials

116

Recruited

49,200+

Published Research Related to This Trial

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]

Fam-trastuzumab deruxtecan-nxki is an effective treatment for advanced HER2-positive breast cancer, showing a response rate of 60.9% in major clinical trials, making it a viable option for patients who have not responded to standard therapies.

While the drug is effective, it comes with potential side effects, including serious risks like interstitial lung disease and left ventricular dysfunction, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Fam-Trastuzumab Deruxtecan-nxki in HER2-Positive Breast Cancer. Nguyen, X., Hooper, M., Borlagdan, JP., 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 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]

Fam-trastuzumab deruxtecan-nxki (ENHERTU) received accelerated FDA approval for treating HER2-positive breast cancer in patients who have already undergone two or more anti-HER2 therapies, based on a study involving 184 patients that showed a confirmed overall response rate of 60.3%.

While ENHERTU is effective, it carries significant risks, including severe interstitial lung disease and neutropenia, highlighting the importance of monitoring for serious side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Fam-Trastuzumab Deruxtecan-Nxki for the Treatment of Unresectable or Metastatic HER2-Positive Breast Cancer. Narayan, P., Osgood, CL., Singh, H., et al.[2022]

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]

Fam-trastuzumab deruxtecan-nxki (T-DXd) has been approved for treating HER2-low metastatic breast cancer, showing significant improvements in progression-free survival (PFS) and overall survival (OS) in a phase III trial with 557 patients.

The study demonstrated a 50% reduction in the risk of disease progression and a 36% reduction in the risk of death compared to standard chemotherapy, with a safety profile consistent with previous uses of T-DXd and no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

US Food and Drug Administration Approval Summary: Fam-Trastuzumab Deruxtecan-nxki for Human Epidermal Growth Factor Receptor 2-Low Unresectable or Metastatic Breast Cancer. Narayan, P., Dilawari, A., Osgood, C., et al.[2023]

Citations

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

Effectiveness of post-trastuzumab deruxtecan treatments ... The EN-SEMBLE study examined the distribution of post-T-DXd treatment regimens, their effectiveness, and the incidence of interstitial lung ...

2. 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 ...

3. 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.

4. enhertuhcp.com enhertuhcp.com/en/breast/efficacy/efficacy-data

Efficacy 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.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40947843/

Real-world safety and efficacy of trastuzumab deruxtecan ... Our study confirms the efficacy and safety of T-DXd in daily clinical practice. Further research and longer patient follow-up are needed to ...

6. enhertuhcp.com enhertuhcp.com/en/nsclc/safety

Safety Data | ENHERTU® (fam-trastuzumab deruxtecan-nxki) Find information about the safety data for ENHERTU. See Prescribing Information, including Boxed WARNINGS.

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

Safety profile of trastuzumab deruxtecan in advanced breast ... The article covers various aspects of T-DXd treatment, including its clinical efficacy, safety profile, and dosing considerations, and provides practical ...

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. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/761139s011lbl.pdf

Trastuzumab deruxtecan - accessdata.fda.gov WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL. TOXICITY. See full prescribing information for complete boxed warning.

10. daiichisankyo.us daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true

Highlights of Prescribing Information In this pooled safety population, the most common (≥20%) adverse reactions (including laboratory abnormalities) were decreased white blood cell count (73%), ...