T-DXd vs. T-DM1 for Residual Breast Cancer

Not currently recruiting at 581 trial locations

Overseen By (Asia sites) Daiichi Sankyo Contact for Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Daiichi Sankyo

Must be taking: Taxane chemotherapy, HER2-directed treatment

Must not be taking: Anti-HER2 ADCs

Disqualifiers: Stage IV BC, Prior breast cancer, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks better treatment options for people with HER2-positive breast cancer who still have cancer after initial chemotherapy. It compares two treatments, trastuzumab deruxtecan (T-DXd) and trastuzumab emtansine (T-DM1), to determine which is more effective and safe. Suitable candidates have HER2-positive breast cancer with remaining cancer despite chemotherapy and surgery. The goal is to reduce the risk of cancer recurrence. As a Phase 3 trial, this study serves as the final step before FDA approval, allowing participants to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether 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 this trial's treatments are likely to be safe?

Research has shown that trastuzumab deruxtecan (T-DXd) is generally well-tolerated and reduces the risk of cancer spreading or returning. In real-world studies, T-DXd proved more effective and maintained a similar safety profile compared to other treatments.

Trials have indicated that trastuzumab emtansine (T-DM1) lowers the chance of cancer recurrence. Long-term studies have confirmed its safety and ongoing benefits for survival rates. While both treatments can cause side effects, these are usually manageable.

Both T-DXd and T-DM1 have good safety records, indicating they are generally safe to use, though side effects can occur. Always discuss with your doctor what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Trastuzumab Deruxtecan (T-DXd) and Trastuzumab Emtansine (T-DM1) offer innovative ways to target residual breast cancer. Unlike the standard of care treatments like chemotherapy or hormone therapy, T-DXd is an antibody-drug conjugate that delivers a potent chemotherapy agent directly to cancer cells, minimizing damage to healthy cells. T-DM1 also uses an antibody-drug conjugate approach but with a different payload, aiming to improve effectiveness and reduce side effects. These treatments are designed to be more precise and potentially more effective, offering new hope for patients with residual breast cancer.

What evidence suggests that this trial's treatments could be effective for residual breast cancer?

This trial will compare trastuzumab deruxtecan (T-DXd) with trastuzumab emtansine (T-DM1) for treating HER2-positive breast cancer. Studies have shown that T-DXd significantly lowers the chance of cancer returning or causing death by 53% compared to T-DM1. T-DM1 also proves effective, improving survival compared to trastuzumab alone. While both treatments are beneficial, T-DXd offers a greater reduction in risk for patients with high-risk, HER2-positive breast cancer who still have invasive disease after initial treatment. Participants in this trial will be randomized to receive either T-DXd or T-DM1. ^{4 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 adults over 18 with HER2-positive breast cancer who didn't have a complete response after neoadjuvant therapy. They should have had surgery to remove the disease, not be stage IV, and must not have received certain drugs like T-DXd or T-DM1 before. Participants need good heart function and no history of severe lung or heart conditions.

Inclusion Criteria

Your heart's pumping function (LVEF) is at least 50% within the last 28 days before joining the study.

My breast cancer has been confirmed by a biopsy.

I still have cancer in my breast or lymph nodes after initial treatment.

Exclusion Criteria

I have had breast cancer before, but not LCIS.

I have had lung inflammation that needed steroids, or it shows on a chest CT scan.

I haven't had a heart attack or severe heart failure in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either trastuzumab deruxtecan (T-DXd) or trastuzumab emtansine (T-DM1) based on randomization

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Trastuzumab Deruxtecan (T-DXd)
• Trastuzumab Emtansine (T-DM1)

Trial Overview The study compares Trastuzumab Deruxtecan (T-DXd) with Trastuzumab Emtansine (T-DM1) in patients at high risk of recurrence after initial treatment for invasive breast cancer. It aims to find out which drug is safer and more effective as a follow-up therapy.

How Is the Trial Designed?

Group I: Trastuzumab deruxtecan (T-DXd) Experimental Treatment 1 Intervention

Participants who will be randomized to receive trastuzumab deruxtecan (T-DXd) at a starting dose of 5.4 mg/kg.

Group II: Trastuzumab ematansine (T-DM1) Active Control 1 Intervention

Participants who will be randomized to receive trastuzumab ematansine (T-DM1) at a starting dose of 3.6 mg/kg.

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

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

GBG Forschungs GmbH

Collaborator

Trials

50

Recruited

47,500+

German Breast Group

Collaborator

Trials

54

Recruited

48,400+

Spanish Breast Cancer Research Group (SOLTI)

Collaborator

Trials

1

Recruited

1,600+

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

NSABP Foundation Inc

Collaborator

Trials

89

Recruited

140,000+

Published Research Related to This Trial

In a comparison of the safety profiles of trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) using data from 3723 and 2045 adverse event reports respectively, T-DXd was associated with higher rates of fatal outcomes in the hematologic and respiratory systems, while T-DM1 had more severe outcomes in the hepatobiliary system.

Both drugs showed distinct adverse event patterns, with T-DM1 linked to nervous and musculoskeletal issues, and T-DXd associated with respiratory and gastrointestinal problems, highlighting the need for careful monitoring of specific risks in patients, especially those over 65 or on certain drug combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Event Profile Differences between Trastuzumab Emtansine and Trastuzumab Deruxtecan: A Real-world, Pharmacovigilance Study. Liu, F., Yin, G., Xue, S., et al.[2023]

Trastuzumab emtansine (T-DM1) can cause lacrimal drainage system stenosis, leading to excessive tearing in patients, as seen in a case study of a 36-year-old woman with metastatic breast cancer.

The condition was successfully treated with a topical steroid (dexamethasone), demonstrating that while T-DM1 is effective for HER2-positive breast cancer, it can have side effects that are manageable with appropriate treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lacrimal drainage system stenosis associated with Trastuzumab emtansine (Kadcyla®, T-DM1) administration: a case report. Kim, CY., Kim, N., Choung, HK., et al.[2020]

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]

Trastuzumab-deruxtecan (T-DXd) is a promising antibody-drug conjugate that shows clinically relevant activity in heavily pretreated patients with HER2-positive metastatic breast cancer, particularly those who have progressed on T-DM1.

While T-DXd demonstrates efficacy, it is important to monitor for interstitial lung disease, which occurred in about 13% of patients, highlighting the need for careful patient management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab-deruxtecan: an investigational agent for the treatment of HER2-positive breast cancer. Bartsch, R.[2022]

In a study of 22 patients with HER2-positive metastatic breast cancer, trastuzumab deruxtecan (T-DXd) showed a median progression-free survival of 9.7 months and an objective response rate of 61.9%, indicating its efficacy as a treatment option.

T-DXd was particularly effective in patients with heterogeneous or reduced HER2 expression, achieving partial responses in patients who did not respond to the previous treatment with ado-trastuzumab emtansine (T-DM1), highlighting its potential to overcome resistance in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impacts of clinicopathological factors on efficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer. Nakajima, H., Harano, K., Nakai, T., 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]

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

2. 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 ...

3. onclive.com onclive.com/view/t-dxd-improves-idfs-and-dfs-vs-t-dm1-in-her2-breast-cancer-with-residual-invasive-disease

T-DXd Improves IDFS and DFS vs T-DM1 in HER2+ Breast ... T-DXd significantly improved IDFS and reduced the risk of invasive disease or death by 53% compared to T-DM1 in high-risk, HER2-positive breast ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12451362/

Real-world efficacy and safety of trastuzumab deruxtecan ... T-DXd was associated with improved treatment persistence and better survival outcomes compared with T-DM1 in the second-line setting and with ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)04968-3/fulltext

Neoadjuvant trastuzumab deruxtecan alone or followed by ... Neoadjuvant T-DXd-THP demonstrated statistically significant and clinically meaningful pCR benefit and improved safety versus ddAC-THP. Keywords.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04622319

NCT04622319 | A Study of Trastuzumab Deruxtecan (T- ... This study will examine the efficacy and safety of trastuzumab deruxtecan (T-DXd) compared with trastuzumab emtansine (T-DM1) in high-risk patients with ...

7. oncologynewscentral.com oncologynewscentral.com/breast-cancer/t-dxd-shows-superiority-in-high-risk-her2-positive-residual-breast-cancer

T-DXd Shows Superiority in High-Risk, HER2-Positive ... Patients treated with adjuvant T-DXd had a 53% reduction in the risk for invasive disease recurrence or death compared with patients treated ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e13024

Trastuzumab deruxtecan (T-DXd) in HER2-positive ... The primary endpoint is median progression-free survival (PFS); secondary endpoints include 12-month intracranial progression-free survival ( ...

9. 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 results from DESTINY-Breast11 show that treatment with Enhertu followed by THP prior to surgery resulted in no evidence of residual invasive ...