Trastuzumab Deruxtecan for Cancer

Recruiting at 8 trial locations

Overseen By Contact for Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Daiichi Sankyo

Disqualifiers: MI, CHF, QT prolongation, ILD, others

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

Compensation: Varies

Number of Visits: Unknown

76 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of delivering the cancer drug Trastuzumab Deruxtecan (an antibody-drug conjugate) to individuals with advanced or metastatic breast cancer that is either HER2-positive or HER2-low. Researchers aim to determine the optimal dose and assess its safety and effectiveness when administered as a subcutaneous injection. Suitable candidates have advanced or metastatic breast cancer that has not responded well to previous treatments, such as chemotherapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants the opportunity to be among the first to receive this new approach.

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's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that trastuzumab deruxtecan (T-DXd) raised some safety concerns in past studies. About 13% of patients developed interstitial lung disease (ILD), where the lungs become inflamed and scarred. Although serious, fatal cases were rare, occurring in less than 1% of patients. Additionally, about 7.1% of patients stopped treatment due to side effects. Severe cases of neutropenia, a dangerously low level of a type of white blood cell, have also been reported.

While these side effects are important to consider, the treatment has been thoroughly studied and is FDA-approved for certain conditions. This approval indicates it has passed strict safety checks for those uses. However, this trial is testing a new method of administering the drug, so safety remains under close observation. ^{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, creating a powerful treatment option for certain cancers. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, this drug specifically targets HER2 proteins on cancer cells, delivering the chemotherapy directly to the tumor. This targeted approach not only increases the effectiveness of the treatment but also reduces damage to healthy cells, potentially leading to fewer side effects. Researchers are particularly excited about its subcutaneous delivery method, which could provide a more convenient and less invasive alternative to intravenous administration.

What evidence suggests that Trastuzumab Deruxtecan might be an effective treatment for metastatic solid tumors?

Research has shown that trastuzumab deruxtecan yields promising results for treating certain cancers. In earlier studies, this treatment reduced the risk of cancer recurrence or death by 53% compared to T-DM1. Patients using trastuzumab deruxtecan in real-world settings experienced about 5 months without disease progression and had an overall survival of about 15 months. However, there is a significant risk of side effects, such as interstitial lung disease (ILD), which affected about 13% of patients in studies. These findings suggest that trastuzumab deruxtecan could effectively treat advanced solid tumors, though side effects require careful management. Participants in this trial will receive trastuzumab deruxtecan either at escalating doses to determine the recommended dose for expansion or at the recommended dose for expansion in the dose expansion phase. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic solid tumors that have come back after previous treatment. Specific details about who can join are not provided, but typically participants must meet certain health standards and may need to have a particular type of tumor marker.

Inclusion Criteria

I am at least 18 years old or the legal adult age in my country.

I have advanced breast cancer with low HER2, treated with ≤2 chemotherapies, and progressed after hormone therapy.

Sign and date the ICF, prior to the start of any trial-specific qualification procedures

Exclusion Criteria

History of severe hypersensitivity reactions to other monoclonal antibodies

Corrected QT interval (QTcF) prolongation to > 480 ms based on average of the screening triplicate 12-lead ECG

History of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug products

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive Trastuzumab Deruxtecan subcutaneously at escalating doses to determine the recommended dose for expansion

Up to 9 months

Dose Expansion

Participants receive Trastuzumab Deruxtecan subcutaneously at the recommended dose for expansion

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

21 days

What Are the Treatments Tested in This Trial?

Interventions

• Trastuzumab Deruxtecan

Trial Overview The study is testing Trastuzumab Deruxtecan (T-DXd) given under the skin with an enzyme called hyaluronidase. It's looking at how safe it is, how well people tolerate it, what happens to it in the body (pharmacokinetics), and if it works against cancer.

How Is the Trial Designed?

Group I: Part 2 (Dose Expansion) Experimental Treatment 1 Intervention

Participants will receive Trastuzumab Deruxtecan subcutaneously at the recommended dose for expansion (RDE)

Group II: Part 1 (Dose Escalation) Experimental Treatment 1 Intervention

Participants will receive Trastuzumab Deruxtecan subcutaneously at escalating doses. The recommended dose for expansion (RDE) will be calculated using data collected from this population.

Who Is Running the Clinical Trial?

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

Citations

1. nature.com nature.com/articles/s41523-025-00841-9

Real-world outcomes of trastuzumab deruxtecan in HR- ... Median real-world progression-free survival (rwPFS) and overall survival were 5.0 months and 14.9 months, respectively. Multivariate analysis ...

2. esmoopen.com esmoopen.com/article/S2059-7029(25)01716-8/fulltext

Real-world safety and efficacy profiles of trastuzumab ... Trastuzumab deruxtecan (T-DXd) is associated with a significant rate of discontinuation (∼7.1%) and ILD (∼13%). •. Safety and efficacy profiles ...

3. 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 ...

4. 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.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41160818/

Trastuzumab Deruxtecan plus Pertuzumab for HER2- ... Trastuzumab deruxtecan plus pertuzumab led to a significantly lower risk of progression or death than THP when used as first-line treatment ...

6. 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) ...

7. 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 ... Fatal outcomes due to ILD and/or pneumonitis occurred in 0.9% of patients treated with ENHERTU. HER2-Positive Locally Advanced or Metastatic ...

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

Safety Data | ENHERTU® (fam-trastuzumab deruxtecan-nxki) Fatal outcomes due to ILD and/or pneumonitis occurred in 0.9% of patients treated with ENHERTU. Neutropenia. Severe neutropenia, including febrile neutropenia, ...