T-DXd for Cancer

Recruiting at 43 trial locations

Overseen By Daiichi Sankyo Contact for Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Daiichi Sankyo, Inc.

Disqualifiers: Unresolved adverse events, Off T-DXd >18 weeks

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: Unknown

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the continued benefits of the cancer drug T-DXd (Trastuzumab deruxtecan) for individuals who have already received it in a previous study. It aims to determine if participants can continue benefiting from T-DXd without experiencing disease progression. The trial suits those currently in a Daiichi Sankyo or Daiichi Sankyo/AstraZeneca sponsored study, who have seen positive results without cancer worsening, and wish to continue using T-DXd. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to the potential approval of a promising treatment.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It seems to focus on continuing treatment from a previous study, so you might be able to stay on your current medications, but it's best to check with the study team.

Is there any evidence suggesting that T-DXd is likely to be safe for humans?

Research has shown that T-DXd, also known as Enhertu, has been thoroughly studied for safety across different patient groups. One study confirmed its effectiveness and safety in everyday medical settings. However, some side effects have been reported. For instance, 65% of patients treated with T-DXd experienced a drop in neutrophil count, a type of white blood cell that helps fight infections. This side effect does not occur in everyone, but awareness is important.

Overall, while T-DXd effectively lowers the risk of cancer recurrence for certain types, monitoring side effects is crucial. Discuss potential risks and benefits with a healthcare provider before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for cancer?

Unlike traditional treatments for cancer, T-DXd, also known as Trastuzumab Deruxtecan, is unique because it combines an antibody with a chemotherapy drug in a targeted approach. This treatment specifically targets cancer cells that overexpress the HER2 protein, which is often associated with aggressive tumor growth. Researchers are excited about T-DXd because it delivers chemotherapy directly to cancer cells, potentially reducing side effects and improving effectiveness compared to standard options like surgery, radiation, or non-targeted chemotherapy. By honing in on cancerous cells while sparing healthy ones, T-DXd offers a promising new strategy for tackling HER2-positive cancers.

What evidence suggests that T-DXd might be an effective treatment for cancer?

Research shows that T-DXd, also known as ENHERTU®, reduces the risk of breast cancer recurrence or death by 53% compared to T-DM1. This indicates a significantly lower chance of cancer returning or becoming life-threatening for those taking T-DXd. One study found that patients typically noticed the treatment's effects after about 5.5 months, suggesting that T-DXd effectively slows the disease. However, serious side effects, such as lung problems, occurred in a small number of patients (0.9%). Overall, strong evidence supports T-DXd's effectiveness in treating certain types of cancer. Participants in this trial will continue treatment with T-DXd, as previous studies have shown promising results. ^{2 6 7 8 9}

Who Is on the Research Team?

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Are You a Good Fit for This Trial?

This trial is for cancer patients who are currently benefiting from ongoing treatment in specific Daiichi Sankyo or DS/Astra Zeneca studies. Participants must have been part of one of the listed trials and continue to see positive effects from the therapy.

Inclusion Criteria

Signed informed consent form, prior to the start of any study-specific qualification procedures and willing to comply with all study requirements.

Currently enrolled in a DS or DS/AZ-sponsored parent study that has met EOS definition.

My condition is stable and I benefit from continuing my current treatment.

Exclusion Criteria

I stopped T-DXd therapy more than 18 weeks ago before starting this study.

I don't have any ongoing side effects that would stop me from taking the study drug.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants continue treatment with T-DXd as per their last dosage regimen from the parent study

Follow-up

Participants are monitored for safety and effectiveness after treatment

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• T-DXd

Trial Overview The study focuses on providing continued access to T-DXd, a drug under investigation, and monitoring its long-term safety for those already receiving it as part of other clinical trials by the same sponsors.

How Is the Trial Designed?

Group I: T-DXd Experimental Treatment 1 Intervention

Participants who choose to continue treatment with T-DXd may be enrolled. Participants who were on the comparator arm in the parent study will be provided the option to access the drug through standard of care (SoC) or other available options. Participants will remain on their current dosage regimen of T-DXd as the last dose administered in the parent study, unless they experience an AE that requires dose reduction at the EOT of the parent study, in which case the starting dose in this study will be the next lower dose-level.

T-DXd is already approved in United States, European Union, Japan for the following indications:

Approved in United States as Enhertu for:

• HER2-positive metastatic breast cancer
• HER2-positive gastric or gastroesophageal adenocarcinoma

Approved in European Union as Enhertu for:

• HER2-positive metastatic breast cancer
• HER2-positive gastric or gastroesophageal adenocarcinoma

Approved in Japan as Enhertu for:

• HER2-positive metastatic breast cancer
• HER2-positive gastric or gastroesophageal adenocarcinoma

Who Is Running the Clinical Trial?

Daiichi Sankyo, Inc.

Lead Sponsor

Trials

390

Recruited

442,000+

Yuki Abe

Daiichi Sankyo, Inc.

Chief Medical Officer since 2022

MD

Hiroyuki Okuzawa

Daiichi Sankyo, Inc.

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Daiichi Sankyo

Lead Sponsor

Trials

443

Recruited

493,000+

Hiroyuki Okuzawa

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

MD

AstraZeneca

Industry 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

Published Research Related to This Trial

Trastuzumab deruxtecan (T-DXd) showed promising antitumor activity in patients with advanced HER2-low breast cancer, achieving a 37% objective response rate in a study of 54 patients who had undergone a median of 7.5 prior therapies.

While T-DXd demonstrated efficacy, it also presented significant safety concerns, with 98% of patients experiencing treatment-emergent adverse events, including severe cases of interstitial lung disease (ILD) that led to fatalities, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low-Expressing Advanced Breast Cancer: Results From a Phase Ib Study. Modi, S., Park, H., Murthy, RK., et al.[2021]

In an expanded-access study involving 64 patients with HER2-positive gastric or gastroesophageal junction adenocarcinomas, trastuzumab deruxtecan (T-DXd) was administered safely, with no new safety concerns identified prior to its marketing approval in Japan.

Serious adverse events (SAEs) were reported in 26.6% of patients, with febrile neutropenia being the most common; however, drug-related SAEs led to death in only one patient, indicating a manageable safety profile for T-DXd.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan in patients with locally advanced or metastatic HER2-positive gastric cancer: a multicenter, open-label, expanded-access study. Shitara, K., Yamaguchi, K., Muro, K., et al.[2023]

In a meta-analysis of 1970 patients with metastatic breast cancer, trastuzumab deruxtecan (T-DXd) was associated with an 11.7% incidence of interstitial lung disease (ILD), with most cases being mild (grade 1 or 2).

The treatment also showed a low incidence of cardiotoxicity, with only 1.95% of patients experiencing decreased left ventricular ejection fraction (LVEF) and 7.77% experiencing QT interval prolongation, indicating that while T-DXd has some risks, serious heart-related side effects are relatively rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of interstitial lung disease and cardiotoxicity with trastuzumab deruxtecan in breast cancer patients: a systematic review and single-arm meta-analysis. Soares, LR., Vilbert, M., Rosa, VDL., et al.[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 the DESTINY-Breast03 trial, trastuzumab deruxtecan (T-DXd) demonstrated superior progression-free survival and overall survival compared to trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer, while maintaining quality of life (QoL) throughout treatment.

Patients receiving T-DXd experienced a median time to first hospitalization that was three times longer than those on T-DM1, indicating better overall health management and fewer hospital visits during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study. Curigliano, G., Dunton, K., Rosenlund, M., et al.[2023]

Trastuzumab deruxtecan (T-DXd) is a promising HER2-targeted therapy that has shown significant anti-tumor activity in heavily pre-treated patients with HER2-positive breast and gastric cancers, and preliminary data suggest it may also be effective in HER2-positive non-small cell lung cancer (NSCLC) and colorectal cancer.

While T-DXd has an acceptable safety profile, there are concerns about serious treatment-emergent adverse events, highlighting the need for careful monitoring in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: Changing the Destiny of HER2 Expressing Solid Tumors. Indini, A., Rijavec, E., Grossi, F.[2021]

Trastuzumab deruxtecan (T-DXd) is effective for breast cancer patients with low ERBB2 positivity (IHC scores of 1+ or 2+), but current standard assays show poor accuracy in distinguishing between low scores (0 and 1+), which could misassign patients for treatment.

In a study involving 18 pathologists assessing 170 breast cancer biopsies, there was only 26% concordance in scoring between 0 and 1+, indicating significant variability in ERBB2 IHC scoring that may impact patient eligibility for T-DXd.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue. Fernandez, AI., Liu, M., Bellizzi, A., et al.[2023]

Trastuzumab deruxtecan (T-DXd) has shown significant antitumor activity in patients with HER2-positive advanced gastric cancer (AGC) who have previously undergone at least two therapies, leading to its approval in Japan and by the US FDA.

The treatment resulted in a higher objective response rate and longer overall survival compared to previous therapies, with an acceptable safety profile, indicating its potential as an effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan for the treatment of HER2-positive gastric cancer. Mishima, S., Shitara, K.[2022]

Trastuzumab deruxtecan (T-DXd) is a promising new antibody-drug conjugate that has been approved for treating HER2-positive metastatic breast cancer and gastric cancer, showing potential for use in other solid tumors as well.

T-DXd is expected to become the standard second-line treatment for HER2-positive metastatic breast cancer and may also benefit patients with hormone receptor-positive and triple-negative breast cancer that express low levels of HER2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan in HER2-positive metastatic breast cancer and beyond. Perez, J., Garrigós, L., Gion, M., et al.[2022]

Citations

1. 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12314378/

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 as the first ...

3. academic.oup.com academic.oup.com/jnci/advance-article/doi/10.1093/jnci/djaf220/8234527

Outcomes of subsequent treatment regimens after ... We identified 793 patients receiving a post-T-DXd treatment. Post-T-DXd treatment outcomes differed significantly by MBC subtype: median rwPFS ...

4. 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 ... Results showed ENHERTU significantly reduced the risk of invasive disease recurrence or death by 53% compared with T-DM1 as a post-neoadjuvant ...

5. 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.

6. enhertuhcp.com enhertuhcp.com/en/breast/safety

Safety Data | ENHERTU® (fam-trastuzumab deruxtecan- ... 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.

7. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2025/enhertu-reduced-the-risk-of-disease-recurrence-or-death-by-53-vs-t-dm1-in-patients-with-high-risk-her2-positive-early-breast-cancer.html

Enhertu reduced the risk of disease recurrence or death by ... Results showed Enhertu significantly reduced the risk of invasive disease recurrence or death by 53% compared with T-DM1 as a post-neoadjuvant ...

8. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06914661

Efficacy and Safety of DS8201 in Metastatic Breast ... Although TDXd has achieved remarkable efficacy in second-line and above advanced HER-2 positive breast cancer, there are often the following problems in the ...

9. 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 ...