T-DXd for Cancer

Recruiting at 32 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

Trial Summary

What is the purpose of this trial?

This open-label, multicenter, rollover study will provide continued treatment for participants deriving benefit from different therapies received in studies sponsored by Daiichi Sankyo, Inc. (DS) or DS/Astra Zeneca (AZ)-sponsored study (eg. DS8201-A-J101, DS8201-A-U201, DS8201-A-U204, DS8201-A-U207, DS8201-A-U303).

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.

What data supports the effectiveness of the drug T-DXd (Trastuzumab deruxtecan) for cancer?

T-DXd has shown effectiveness in treating HER2-positive metastatic breast cancer, with a 60.3% overall response rate and a median duration of response of 14.8 months in clinical trials. It has also demonstrated superior progression-free and overall survival compared to another treatment, trastuzumab emtansine, in similar patients. ^{1 2 3 4 5}

What safety data exists for T-DXd (Trastuzumab deruxtecan) in humans?

T-DXd has been associated with serious side effects like interstitial lung disease (a lung condition that can be severe or life-threatening) and cardiotoxicity (heart damage). Other common side effects include nausea, fatigue, vomiting, hair loss, constipation, decreased appetite, anemia (low red blood cell count), diarrhea, and low platelet count. Despite these risks, it has an acceptable safety profile for treating certain cancers. ^{1 2 4 6 7}

What makes the drug T-DXd unique for cancer treatment?

T-DXd is unique because it is an antibody-drug conjugate that specifically targets HER2 (a protein that can promote the growth of cancer cells) and delivers a powerful chemotherapy agent directly to the cancer cells. This targeted approach can be more effective and potentially less harmful to healthy cells compared to traditional chemotherapy. ^{1 4 5 8 9}

Research Team

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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) 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 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]

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]

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]

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]

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]

References

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

FDA Approval Summary: Fam-Trastuzumab Deruxtecan-Nxki for the Treatment of Unresectable or Metastatic HER2-Positive Breast Cancer. [2022]

2. 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]

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

Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue. [2023]

4. United States 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. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan in HER2-positive metastatic breast cancer and beyond. [2022]

6. England 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. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: Changing the Destiny of HER2 Expressing Solid Tumors. [2021]

8. Japan 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. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan for the treatment of HER2-positive gastric cancer. [2022]