Trastuzumab Deruxtecan + Anastrozole for Breast Cancer
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Jonsson Comprehensive Cancer Center
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This phase II trial investigates how well trastuzumab deruxtecan works alone or in combination with anastrozole in treating patients with HER2 low, hormone receptor positive breast cancer. Trastuzumab deruxtecan is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug called deruxtecan. Trastuzumab attaches to HER2 expressed at low levels on cancer cells in a targeted way and delivers deruxtecan to kill them. Anastrozole works by decreasing estrogen production and suppressing the growth of tumors that need estrogen to grow. This study is evaluating how effective trastuzumab deruxtecan is at treating hormone receptor positive cancer cells that have low levels of HER2 expressed on them when given alone or in combination with anastrozole.
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 studies indicating prolonged progression-free survival and a generally manageable safety profile. It has been approved for use in patients who have previously received other anti-HER2 treatments.
13468How is the drug Trastuzumab Deruxtecan + Anastrozole unique for breast cancer treatment?
Trastuzumab Deruxtecan is a novel drug that combines a HER2-targeted antibody with a powerful cancer-killing agent, making it effective for patients with HER2-positive breast cancer who have already tried other treatments. It is unique because it targets cancer cells more precisely, potentially leading to better outcomes for those with advanced or metastatic breast cancer.
12346Is Trastuzumab Deruxtecan + Anastrozole 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 HER2-positive breast cancer. Common side effects include nausea, fatigue, and hair loss, with some risk of lung-related issues like interstitial lung disease or pneumonitis, which require careful monitoring.
14567Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, there is a required washout period for certain treatments, like major surgery and chloroquine/hydroxychloroquine, before joining the trial.
Eligibility Criteria
This trial is for postmenopausal women or those willing to undergo ovarian suppression, with early-stage HER2 low, hormone receptor-positive breast cancer. They should have good physical function and no severe medical conditions that could interfere with the study. Participants must not have had certain prior treatments or conditions like active infections, recent heart issues, or a history of severe allergies to similar drugs.Inclusion Criteria
I haven't had major surgery in the last 4 weeks or taken Chloroquine/hydroxychloroquine in the last 14 days.
My tumor is hormone receptor positive for estrogen and progesterone.
My white blood cell count is healthy without recent medication to increase it.
I am fully active or restricted in physically strenuous activity but can do light work.
My cancer has not spread beyond nearby lymph nodes according to my latest scans.
My breast cancer is larger than 2 cm and has not been treated yet.
My estradiol levels are in the post-menopausal range.
Exclusion Criteria
I have inflammatory breast cancer.
I have had treatment that goes through my whole body for cancer.
I have had a stem-cell transplant.
I have severe lung problems or lung-related autoimmune diseases.
I have taken tamoxifen for DCIS but no other breast cancer treatments.
I have had radiation therapy on the same side of my chest before.
I have a blood clotting disorder and am on blood thinners.
I do not have any active infections requiring IV antibiotics or known viral infections like HIV or active hepatitis B or C.
I cannot swallow pills.
I haven't had a heart attack or severe heart failure in the last 6 months.
I don't have severe gut issues that affect how I absorb pills.
My breast cancer has returned or spread to other parts.
Participant Groups
The effectiveness of Trastuzumab Deruxtecan alone or combined with Anastrozole is being tested in patients with specific breast cancer types. Trastuzumab Deruxtecan targets and delivers chemotherapy directly to cancer cells while Anastrozole suppresses tumor growth by reducing estrogen production.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm B (trastuzumab deruxtecan, anastrozole)Experimental Treatment3 Interventions
Patients receive trastuzumab deruxtecan IV over 90 minutes on cycle 1 day 1 and 30 minutes on day 1 of each subsequent cycle and anastrozole PO QD on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery.
Group II: Arm A (trastuzumab deruxtecan)Active Control2 Interventions
Patients receive trastuzumab deruxtecan IV over 90 minutes on cycle 1 day 1 and 30 minutes on day 1 of each subsequent cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery.
Anastrozole is already approved in European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Arimidex for:
- Breast cancer
- Early breast cancer in postmenopausal women
🇺🇸 Approved in United States as Arimidex for:
- Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
- First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer
🇨🇦 Approved in Canada as Arimidex for:
- Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
- Treatment of postmenopausal women with hormone receptor-positive advanced breast cancer
🇯🇵 Approved in Japan as Arimidex for:
- Breast cancer
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
PIH HealthWhittier, CA
UCLA / Jonsson Comprehensive Cancer CenterLos Angeles, CA
St. Joseph Heritage HealthcareFullerton, CA
Torrance Memorial Physician Network / Cancer CareTorrance, CA
More Trial Locations
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Who is running the clinical trial?
Jonsson Comprehensive Cancer CenterLead Sponsor
Translational Research in Oncology-U.SCollaborator
Daiichi Sankyo Co., Ltd.Industry Sponsor
References
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) 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.
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: 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.
Safety of trastuzumab deruxtecan: A meta-analysis and pharmacovigilance study. [2023]This study aimed to explore the safety profile of trastuzumab deruxtecan (T-DXd, formerly DS-8201a) using multi-source medical data.
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.
Efficacy and safety of trastuzumab deruxtecan in the treatment of HER2-low/positive advanced breast cancer: a single-arm meta-analysis. [2023]Background: Clinical trials have shown that the use of trastuzumab deruxtecan (DS-8201) alone is expected to provide novel therapeutic options for HER2-low/positive patients. Nevertheless, there are some variations in the efficacy of trial results, with potential risks at the safety level. Most DS-8201 trials in HER2 advanced breast cancer (ABC) have been conducted in the form of small-sample nonrandomized controlled studies, resulting in a lack of validated indicators to evaluate the efficacy and safety of DS-8201. Thus, this meta-analysis aimed to pool the results of various trials of DS-8201 alone to explore the efficacy and safety of DS-8201 in patients with HER2-low/positive advanced breast cancer. Methods: Relevant studies were searched in seven databases, including Embase, PubMed, Web of Science, Cochrane Library, CNKI, VIP database and WanFang data, to collect single-arm studies on DS-8201 for HER2-low/positive ABC. MINORS was adopted for quality assessment and STATA 16.0 for data analysis. Results: Ten studies involving 1,108 patients were included in this meta-analysis. As for the tumor response rate, the pooled ORR and DCR of all studies reached 57% (95% CI: 47%-67%) and 92% (95% CI: 89%-96%) respectively, and the pooled ORRs of the HER2-low expression group and the HER2-positive expression group were 46% (95% CI: 35%-56%) and 64% (95% CI: 54%-74%). Only the low expression group achieved median survival time, with a pooled median PFS and median OS of 9.24 (95% CI: 7.54-10.94) months and 23.87 (95% CI: 21.56-26.17) months, respectively. The most common treatment-related adverse events from DS-8201 were nausea (all grades: 62%; ≥ grade III: 5%), fatigue (all grade: 44%; ≥ grade III: 6%), and alopecia (all grades: 38%; ≥ grade III: 0.5%). Drug-related interstitial lung disease or pneumonitis occurred in 13% of the 1,108 patients, with only a 1% incidence of AE ≥ grade III. Conclusion: The present study suggests that DS-8201 is effective and safe in the treatment of ABC with low or positive HER2 expression, providing additional relevant information for its clinical application. However, further strengthening of the pairs is needed, as well as more clinical studies to support individualized treatment. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023390316.
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.