Trastuzumab Deruxtecan for Breast Cancer
Recruiting in Palo Alto (17 mi)
+68 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Daiichi Sankyo
Must not be taking: Antibody drug conjugates
Disqualifiers: Cardiovascular disease, ILD, CNS metastases, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?This study will evaluate the safety and efficacy of trastuzumab deruxtecan (T-DXd) in participants with human epidermal growth factor receptor 2 (HER2)-low or HER2 immunohistochemistry (IHC) 0 (who are both hormone receptor \[HR\]-negative and HR-positive) unresectable and/or metastatic breast cancer.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, it mentions that there should be an adequate treatment washout period before enrollment, which might mean you need to stop certain medications for a time before starting the trial.
What data supports the effectiveness of the drug Trastuzumab Deruxtecan for breast cancer?
Trastuzumab Deruxtecan has shown effectiveness in treating HER2-positive breast cancer, with a phase 3 trial demonstrating longer progression-free survival compared to another treatment, trastuzumab emtansine. Additionally, a phase 2 trial reported a 60% overall response rate and 97% disease control in patients who had previously received multiple treatments.
12345Is Trastuzumab Deruxtecan safe for humans?
Trastuzumab Deruxtecan, also known as Enhertu or DS-8201a, has been shown to have a generally manageable safety profile in clinical trials for breast and gastric cancers. Common side effects include blood and stomach-related issues, and there is a warning for lung problems (interstitial lung disease/pneumonitis) and potential harm to unborn babies.
12467What makes the drug Trastuzumab Deruxtecan unique for treating breast cancer?
Trastuzumab Deruxtecan is unique because it is an antibody-drug conjugate that combines a HER2-targeted antibody with a powerful cancer-killing agent, offering a new option for patients with HER2-positive breast cancer who have already tried other treatments. It has shown effectiveness in prolonging progression-free survival compared to previous therapies and is administered intravenously.
12347Eligibility Criteria
This trial is for adults with unresectable/metastatic breast cancer that's either hormone receptor-negative or -positive but HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2 IHC 0. Participants must not have been previously treated with anti-HER2 therapy in the metastatic setting and should have had one to two prior lines of therapy for their metastatic disease.Inclusion Criteria
My cancer returned within 2 years after starting hormone therapy, or it got worse within 12 months after or during a specific treatment.
My cancer is confirmed as HER2-low or HER2-negative.
My cancer may or may not respond to hormones.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Trastuzumab Deruxtecan (T-DXd) for the treatment of unresectable and/or metastatic HER2-low or HER2 IHC 0 breast cancer
Up to 24 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 24 months
Participant Groups
The study tests Trastuzumab Deruxtecan (T-DXd) on patients with specific types of breast cancer. It aims to assess how safe and effective T-DXd is in treating those whose tumors are low in a protein called HER2, which can affect cancer growth.
4Treatment groups
Experimental Treatment
Group I: Cohort 4: HR-positive, HER2 IHC 0Experimental Treatment1 Intervention
Participants with HR-positive HER2 IHC 0 unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd.
Group II: Cohort 3: HR-positive, HER2-lowExperimental Treatment1 Intervention
Participants with HR-positive HER2-low unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd.
Participants must also have recurrent disease \<2 years from the initiation of adjuvant ET or have disease progression on CDK4/6 inhibitor-based regimen within 12 months of completion of adjuvant therapy with a CDK4/6 inhibitor or have disease progression within the first 12 months of CDK4/6 in the first line metastatic setting.
Group III: Cohort 2: HR-negative, HER2 IHC 0Experimental Treatment1 Intervention
Participants with HR-negative HER2 IHC 0 unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd.
Group IV: Cohort 1: HR-negative, HER2-lowExperimental Treatment1 Intervention
Participants with HR-negative HER2-low unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd.
Trastuzumab Deruxtecan is already approved in European Union, United States, Japan for the following indications:
🇪🇺 Approved in European Union as Enhertu for:
- Unresectable or metastatic HER2-positive breast cancer
- Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma
🇺🇸 Approved in United States as Enhertu for:
- Unresectable or metastatic HER2-positive breast cancer
- Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma
- HER2-low breast cancer
🇯🇵 Approved in Japan as Enhertu for:
- Unresectable or metastatic HER2-positive breast cancer
- Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Beth Israel Lahey HealthBurlington, MA
USF College of MedicineTampa, FL
Overlook Medical CenterSummit, NJ
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Who Is Running the Clinical Trial?
Daiichi SankyoLead Sponsor
Daiichi Sankyo, Inc.Lead Sponsor
AstraZenecaIndustry Sponsor
References
Trastuzumab Deruxtecan: First Approval. [2020]Trastuzumab deruxtecan (ENHERTU®), a HER2-directed antibody and DNA topoisomerase I inhibitor conjugate, is being developed for the treatment of HER2-expressing solid tumours, including breast cancer, gastric cancer, colorectal cancer and non-small cell lung cancer by Daiichi Sankyo Company Ltd in collaboration with AstraZeneca. Based primarily on the results of the phase 2 DESTINY-Breast01 trial, trastuzumab deruxtecan was recently approved in the USA under accelerated approval for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. This article summarizes the milestones in the development of trastuzumab deruxtecan leading to this first approval.
Trastuzumab Deruxtecan: A Review in Unresectable or Metastatic HER2-Positive Breast Cancer. [2023]Trastuzumab deruxtecan (Enhertu®) is a human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate approved in several countries, including the USA and those of the EU, for adults with unresectable or metastatic HER2-positive breast cancer who have previously received at least one prior anti-HER2-based regimen. In a pivotal phase 3 trial in this setting, intravenous trastuzumab deruxtecan demonstrated prolonged progression-free survival compared with trastuzumab emtansine (previously the recommended second-line therapy in this indication). Trastuzumab deruxtecan had a generally manageable safety and tolerability profile. Common treatment-related adverse events included haematological and gastrointestinal disorders. Interstitial lung disease (ILD)/pneumonitis is associated with a regulatory warning and requires careful monitoring. In conclusion, trastuzumab deruxtecan is a valuable new treatment option for HER2-positive breast cancer, having been shown to be effective with a generally manageable safety and tolerability profile in adults with unresectable or metastatic disease who have received one or more prior anti-HER2-based regimens.
Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. [2021]Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate composed of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor. In a phase 1 dose-finding study, a majority of the patients with advanced HER2-positive breast cancer had a response to trastuzumab deruxtecan (median response duration, 20.7 months). The efficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab emtansine requires confirmation.
Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. [2020]Trastuzumab deruxtecan (DS-8201a) is a novel HER2-targeted antibody-drug conjugate with a humanised anti-HER2 antibody, cleavable peptide-based linker, and potent topoisomerase I inhibitor payload. A phase 1, non-randomised, open-label, multiple-dose study was done to assess the safety, tolerability, and activity of trastuzumab deruxtecan in HER2-expressing, advanced solid tumours. The dose escalation (part 1) has previously been reported and the recommended doses for expansion of 5·4 mg/kg or 6·4 mg/kg were established. In this Article, we report the safety and preliminary activity results from this phase 1 trial in all patients with HER2-positive advanced-stage breast cancer with previous trastuzumab emtansine treatment who received trastuzumab deruxtecan at the recommended doses for expansion.
Trastuzumab Deruxtecan (DS-8201a): The Latest Research and Advances in Breast Cancer. [2021]The development of antibody-drug conjugates composed of a cytotoxic agent and a monoclonal antibody carrier offers an important alternative to classic chemotherapy strategies. Trastuzumab deruxtecan (DS-8201a) is a next-generation antibody-drug conjugate composed of a monoclonal anti-HER2 antibody and a topoisomerase I inhibitor, an exatecan derivative (DX-8951f). DS-8201a resulted in favorable outcomes in HER2-positive heavily pretreated breast cancer patients and also had a promising efficacy in patients with HER2-negative/low-expressing disease, whose options are limited. Interestingly, a recently published phase 2 trial (NCT03248492) reported 60% overall response and 97% disease control in patients with HER2-positive disease previously treated with multiple regimens, including trastuzumab emtansine. On the basis of recent clinical trials, the US Food and Drug Administration granted accelerated approval to DS-8201a in advanced or unresectable HER2-positive breast cancer pretreated with at least two HER2-targeting treatment lines. We review all preclinical and clinical data of DS-8201a regarding breast cancer.
Trastuzumab Deruxtecan: A Review in Gastric or Gastro-Oesophageal Junction Adenocarcinoma. [2023]Trastuzumab deruxtecan (Enhertu®) is a human epidermal growth factor receptor type 2 (HER2)-directed antibody-drug conjugate that is approved in several countries globally for adults with advanced HER2-positive gastric or gastro-oesophageal junction (GOJ) adenocarcinoma who have received a prior trastuzumab-based regime. In the phase II DESTINY-Gastric01 trial, intravenous trastuzumab deruxtecan was significantly more effective than standard chemotherapy (physician's choice of intravenous irinotecan or paclitaxel) in achieving objective response and improving overall survival in Japanese or South Korean adults with advanced HER2-positive gastric or GOJ adenocarcinoma who had received two or more previous therapies. In the phase II DESTINY-Gastric02 trial, trastuzumab deruxtecan was able to induce durable response in adults from the USA or Europe with unresectable or metastatic HER2-positive gastric or GOJ adenocarcinoma. Trastuzumab deruxtecan was generally tolerable in these patients; the most common adverse events included nausea, neutropenia, fatigue and decreased appetite. Trastuzumab deruxtecan carries regulatory warnings (including boxed warnings in the USA) for interstitial lung disease/pneumonitis and embryo-foetal toxicity. Current evidence indicates that trastuzumab deruxtecan is an effective treatment option, and is generally tolerable, in previously treated adults with advanced HER2-positive gastric or GOJ adenocarcinoma.
Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. [2020]Trastuzumab deruxtecan (DS-8201a) is a novel HER2-targeted antibody-drug conjugate with a humanised anti-HER2 antibody, cleavable peptide-based linker, and topoisomerase I inhibitor payload. A phase 1, non-randomised, open-label, multiple-dose study was done to assess the safety, tolerability, and activity of trastuzumab deruxtecan in HER2-expressing advanced solid tumours. The dose escalation (part 1) has previously been reported and the recommended doses for expansion of 5·4 mg/kg or 6·4 mg/kg were established. In this Article, we report the safety and preliminary activity results from this phase 1 trial in all patients with HER2-positive gastric or gastro-oesophageal junction cancer who received trastuzumab deruxtecan at the recommended doses for expansion.