T-DXd vs T-DM1 for HER2-Positive Breast Cancer

Recruiting at 170 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Daiichi Sankyo

Must not be taking: Corticosteroids, Anticonvulsants

Disqualifiers: Cardiovascular disease, ILD, CNS metastases, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

Duration: Up to 33 months

524 Participants Needed

Trial Summary

Do I need to stop my current medications for 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.

What data supports the effectiveness of the drug T-DXd for HER2-positive breast cancer?

In the DESTINY-Breast03 clinical trial, trastuzumab deruxtecan (T-DXd) showed better progression-free survival and overall survival compared to trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer. ^{1 2 3 4 5}

What is the safety profile of T-DXd and T-DM1 in humans?

T-DXd (trastuzumab deruxtecan) and T-DM1 (ado-trastuzumab emtansine) have different safety profiles. T-DXd is associated with lung-related issues like interstitial lung disease and pneumonitis, while T-DM1 is linked to liver-related problems. Both drugs can have serious side effects, especially in older adults and those taking certain other medications. ^{1 2 3 4 6}

What makes the drug T-DXd unique for treating HER2-positive breast cancer?

T-DXd is unique because it is designed to overcome resistance to T-DM1, a previous treatment, by having a higher drug-to-antibody ratio and better ability to penetrate cell membranes, which enhances its effectiveness even in tumors with reduced HER2 expression. ^{1 3 7 8 9}

What is the purpose of this trial?

This trial compares two drugs, DS-8201a and T-DM1, for treating a specific type of breast cancer that hasn't responded to other treatments. These drugs work by targeting a protein on cancer cells to deliver a toxic substance that kills the cancer. T-DM1 has shown significant improvements in patients with HER2-positive breast cancer who have not responded to previous treatments.

Research Team

Global Team Leader

Principal Investigator

Daiichi Sankyo

Eligibility Criteria

This trial is for adults with HER2-positive, unresectable or metastatic breast cancer who have previously been treated with trastuzumab and taxane. They must have adequate organ function and agree to use effective contraception. Those with symptomatic brain metastases, a history of certain lung conditions, uncontrolled heart disease, or previous anti-HER2 ADC treatment in the metastatic setting are excluded.

Inclusion Criteria

My kidney and liver are functioning well.

I am legally considered an adult in my country.

My cancer is confirmed HER2-positive by specific guidelines.

Exclusion Criteria

I have or had lung inflammation that needed steroids, or it might be seen in my recent lung scans.

I have untreated, symptomatic brain or spinal cord metastases requiring medication.

I have been treated with an anti-HER2 drug for cancer that has spread.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either DS-8201a or T-DM1 for HER2-positive, unresectable and/or metastatic breast cancer

Up to 33 months

Every 3 weeks (Q3W) for T-DXd

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ado-trastuzumab emtansine (T-DM1)
• Trastuzumab deruxtecan (DS-8201a)
• Trastuzumab deruxtecan (T-DXd)

Trial Overview The study compares DS-8201a (Trastuzumab deruxtecan) against T-DM1 (Ado-trastuzumab emtansine) in terms of tumor control and overall safety for patients with advanced HER2-positive breast cancer that has not responded to initial treatments.

Participant Groups

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

Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).

Group II: Ado-trastuzumab emtansine (T-DM1) Active Control 1 Intervention

Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DM1 in accordance with the approved label.

Ado-trastuzumab emtansine (T-DM1) is already approved in United States, European Union for the following indications:

Approved in United States as Kadcyla for:

• HER2-positive, metastatic breast cancer

Approved in European Union as Kadcyla for:

• HER2-positive, metastatic breast cancer

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

Daiichi Sankyo Co., Ltd.

Industry Sponsor

Trials

116

Recruited

49,200+

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

Findings from Research

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]

Ado-trastuzumab emtansine (T-DM1) was approved in the U.S. for treating HER2 positive metastatic breast cancer based on the EMILIA phase III trial, which showed it was more effective than the standard treatment of lapatinib plus capecitabine.

Ongoing and planned trials are exploring T-DM1's use in various stages of breast cancer, and the review discusses its toxicity management and potential resistance mechanisms, highlighting its importance in current cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ado-trastuzumab emtansine (T-DM1) in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer: latest evidence and clinical potential. Peddi, PF., Hurvitz, SA.[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]

In a study of 128 patients with advanced HER2+ breast cancer treated with ado-trastuzumab emtansine (T-DM1), the median progression-free survival was 8.7 months and overall survival was 20.4 months, indicating its efficacy in a real-world setting.

The safety profile of T-DM1 was consistent with existing literature, but the study noted higher rates of peripheral neuropathy (21.9%) and liver toxicity (19.5%), which are important considerations for its use in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of T-DM1 in patients with advanced HER2-positive breast cancer The Royal Marsden experience. Battisti, NML., Rogerson, F., Lee, K., et al.[2021]

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 deruxtecan (T-DXd) has shown superior efficacy compared to capecitabine-based chemotherapy and T-DM1 in patients with metastatic HER2-positive breast cancer, based on the latest phase III data from the DESTINY-Breast02 and DESTINY-Breast03 trials.

T-DXd may also be effective as a neoadjuvant treatment for HER2-low breast cancer, suggesting its potential for broader applications in HER2-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-DXd Keeps Shining in Breast Cancer. [2023]

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]

Fam-trastuzumab deruxtecan (T-DXd) is an effective treatment for HER2-positive breast cancer, showing significant clinical activity in advanced cases and in patients with HER2-low disease, based on recent studies.

The toxicity of T-DXd is manageable, with fewer side effects reported when used as an earlier line of therapy, suggesting it may be safer and more beneficial for patients compared to later treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring DESTINY: the Past, Present, and Future of Trastuzumab Deruxtecan. Ali, A., Graff, SL.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Impacts of clinicopathological factors on efficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Ado-trastuzumab emtansine (T-DM1) in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer: latest evidence and clinical potential. [2022]

3. England 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of T-DM1 in patients with advanced HER2-positive breast cancer The Royal Marsden experience. [2021]

5. Brazil pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of Ado-trastuzumab emtansine for the treatment of residual invasive HER2-positive breast cancer. [2022]

6. Australia pubmed.ncbi.nlm.nih.gov

Adverse Event Profile Differences between Trastuzumab Emtansine and Trastuzumab Deruxtecan: A Real-world, Pharmacovigilance Study. [2023]

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

T-DXd Keeps Shining in Breast Cancer. [2023]

8. England pubmed.ncbi.nlm.nih.gov

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

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

Exploring DESTINY: the Past, Present, and Future of Trastuzumab Deruxtecan. [2023]