A Phase 3b, Multicenter, Global, Interventional, Open-label Study of Trastuzumab Deruxtecan (T-DXd), an Anti-HER2-Antibody Drug Conjugate (ADC), in Subjects Who Have Unresectable and/or Metastatic HER2-low or HER2 Immunohistochemistry (IHC) 0 Breast Cancer (DESTINY-Breast15)
New Trial Tests Targeted Therapy for Advanced HER2-Low Breast Cancer
Plain English Summary
Trastuzumab Deruxtecan (T-DXd) in Patients Who Have Hormone Receptor-negative and Hormone Receptor-positive HER2-low or HER2 IHC 0 Metastatic Breast Cancer is a Phase 3 clinical trial sponsored by Daiichi Sankyo studying Breast Cancer. This trial is testing a drug called trastuzumab deruxtecan (T-DXd) to see how well it works and how safe it is for advanced breast cancer. It is for patients with breast cancer that is considered HER2-low or HER2-negative, and has spread or cannot be removed by surgery. Participants will receive T-DXd through an IV drip every three weeks until their cancer progresses, they experience unacceptable side effects, or for up to two years. There are no specific alternative treatments mentioned in this trial description, but standard care options may exist outside of this study. The trial aims to enroll 250 participants.
Official Summary
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.
Who Can Participate
Here is what you need to know about eligibility for this trial. Patients with breast cancer that has spread or cannot be removed by surgery. The cancer must be classified as HER2-low (IHC 1+ or 2+/ISH-) or HER2-negative (IHC 0). Patients must not have had prior treatment with anti-HER2 therapy in the metastatic setting. Patients must have had one or two previous treatments for their metastatic breast cancer. This trial is studying Breast Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.
What They're Measuring
The primary outcome measures how long patients live without their cancer getting worse or needing new treatment, which is important for understanding how effective the drug is in controlling the disea The specific primary outcome measures are: Time From the Start of T-DXd to Initiation of Subsequent Anticancer Treatment (TTNT) (Until subsequent therapy or death, assessed up to 24 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.
About This Phase
This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.
Why This Trial Matters
This trial addresses a significant unmet need by investigating a promising targeted therapy for a large subgroup of breast cancer patients with limited treatment options. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Breast Cancer, where improved treatment options are needed.
Investor Insight
This trial targets a large and growing market for HER2-low breast cancer treatments, with T-DXd showing significant promise and potentially capturing a substantial market share. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.
Is This Trial Right for Me?
Ask your doctor if this trial is a good fit for you, considering your specific cancer type and treatment history. Participation involves regular clinic visits for IV infusions, scans to monitor your cancer, and blood tests to check your overall health. You will need to provide a recent tumor biopsy and potentially an archival sample for testing. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.
AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.
Study Design
- Study Type: INTERVENTIONAL
- Allocation: NON_RANDOMIZED
- Model: PARALLEL
- Masking: NONE
- Enrollment: 250 participants
Interventions
- DRUG: Trastuzumab Deruxtecan — Intravenous administration, 5.4 mg/kg on Day 1 of each 21-day cycle until radiographic disease progression as assessed by the investigator, unacceptable toxicity, other discontinuation criteria are met, or 2 years after first dose of study drug
Primary Outcomes
- Time From the Start of T-DXd to Initiation of Subsequent Anticancer Treatment (TTNT) (Until subsequent therapy or death, assessed up to 24 months)
Secondary Outcomes
- Real-World Progression Free Survival (PFS) (Until progression or death, assessed up to 24 months)
- Time From Start of T-DXd to Discontinuation of T-DXd or Death (TTD) (Until treatment discontinuation or death, up to 24 months)
- Objective Response Rate (ORR) (Until progression, assessed up to 24 months)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Up to follow up period, up to 24 months)
- Mean Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ)-C30 Score (Assessed up to 24 months)
Full Eligibility Criteria
Inclusion Criteria:
* Sign and date the main informed consent form
* Must agree to provide a newly obtained or archival baseline biopsy from primary and/or metastatic lesion.
* Pathologically documented Breast Cancer (BC) tumor
* Is unresectable and/or metastatic.
* Is hormone receptor-negative or hormone receptor-positive.
* Must include percentage of positively stained cells to characterize if hormone receptor-positive or -negative.
* Has confirmed HER2 IHC 1+ or IHC 2+/ISH- (HER2-low) status or HER2 IHC 0 status as determined according to ASCO CAP 2018 guidelines1 based on sample collected during Tissue Screening as described above.
* Was never previously HER2-positive (IHC 3+ or IHC 2+/ISH+) on prior pathology testing (per ASCO CAP guidelines).
* Was never previously treated with anti-HER2 therapy in the metastatic setting.
* Has had at least one and up to two prior lines of therapy in the metastatic setting.
* In participants with hormone receptor-positive HER2-low metastatic BC (Cohort 3):
* Has recurrent disease \<2 years from the initiation of adjuvant ET OR
* Has disease progression on CDK4/6 inhibitor-based regimen within 12 months of completion of adjuvant therapy with a CDK4/6 inhibitor OR
* Has disease progression within the first 12 months of CDK4/6 in the first line metastatic setting
* Presence of at least one measurable lesion based on computed tomography or magnetic resonance imaging.
* Participants with brain metastases are allowed in the study. The brain lesion(s) should be small (\<2 cm), untreated, asymptomatic, not requiring urgent medical intervention, and are asymptomatic and clinically stable.
* Has an Eastern Cooperative Oncology Group performance status of 0 or 1.
* Has a minimum life expectancy of 12 weeks at Screening.
* Has a left ventricular ejection fraction ≥50% within 28 days before enrollment.
* Has adequate organ and bone marrow function within 28 days before enrollment.
* Has adequate treatment washout period before enrollment.
* Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception.
Exclusion Criteria:
* Prior treatment with an antibody drug conjugate (ADC).
* Uncontrolled or significant cardiovascular disease.
* Has a corrected QT interval prolongation.
* Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
* Has spinal cord compression or clinically active central nervous system metastases.
* Has multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, other solid tumors curatively treated, or contralateral BC.
* Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product.
* Has a history of severe hypersensitivity reactions to other monoclonal antibodies.
* Has an uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals.
* Active primary immunodeficiency, known uncontrolled active human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.
* Has history of receiving a live, attenuated vaccine (messenger RNA and replication-deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to study drug.
* Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤1 or baseline.
* Is pregnant or breastfeeding or planning to become pregnant.
* Lung-specific intercurrent clinically significant illnesses.
* Any autoimmune, connective tissue, or inflammatory disorders.
* Prior complete pneumonectomy.Trial Locations
- Mount Sinai Medical Center, Miami Beach, Florida, United States
- USF College of Medicine, Tampa, Florida, United States
- Dana-Farber Cancer Institute, Boston, Massachusetts, United States
- Beth Israel Lahey Health, Burlington, Massachusetts, United States
- Overlook Medical Center, Summit, New Jersey, United States
- Mater Hospital Sydney, North Sydney, New South Wales, Australia
- Monash Medical Centre Moorabbin, East Bentleigh, Victoria, Australia
- GenesisCare St Andrews Hospital, Adelaide, Australia
- Fiona Stanley Hospital, Murdoch, Australia
- Institut Jules Bordet, Anderlecht, Belgium
- ...and 10 more locations
Frequently Asked Questions
What is clinical trial NCT05950945?
NCT05950945 is a Phase 3 INTERVENTIONAL study titled "Trastuzumab Deruxtecan (T-DXd) in Patients Who Have Hormone Receptor-negative and Hormone Receptor-positive HER2-low or HER2 IHC 0 Metastatic Breast Cancer." It is currently recruiting and is sponsored by Daiichi Sankyo. The trial targets enrollment of 250 participants.
What conditions does NCT05950945 study?
This trial investigates treatments for Breast Cancer. The primary condition under study is Breast Cancer.
What treatments are being tested in NCT05950945?
The interventions being studied include: Trastuzumab Deruxtecan (DRUG). Intravenous administration, 5.4 mg/kg on Day 1 of each 21-day cycle until radiographic disease progression as assessed by the investigator, unacceptable toxicity, other discontinuation criteria are met, or 2 years after first dose of study drug
What does Phase 3 mean for NCT05950945?
Phase 3 trials are large-scale studies involving 300-3,000+ patients that compare the new treatment against existing standard treatments. Positive Phase 3 results are typically required for FDA approval.
What is the current status of NCT05950945?
This trial is currently "Recruiting." It started on 2023-12-30. The estimated completion date is 2027-10-01.
Who is sponsoring NCT05950945?
NCT05950945 is sponsored by Daiichi Sankyo. The sponsor is responsible for funding, designing, and overseeing the clinical trial.
How many people can participate in NCT05950945?
The trial aims to enroll 250 participants. The trial is currently recruiting and accepting new participants.
How is NCT05950945 designed?
This is a interventional study, uses non_randomized allocation, follows a parallel design, employs none masking.
What are the primary outcomes being measured in NCT05950945?
The primary outcome measures are: Time From the Start of T-DXd to Initiation of Subsequent Anticancer Treatment (TTNT) (Until subsequent therapy or death, assessed up to 24 months). These are the main endpoints researchers use to determine whether the treatment is effective.
Where is NCT05950945 being conducted?
This trial is being conducted at 20 sites, including Miami Beach, Florida; Tampa, Florida; Boston, Massachusetts; Burlington, Massachusetts and 16 more sites (United States, Australia, Belgium).
Where can I find official information about NCT05950945?
The official record for NCT05950945 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT05950945. This government database provides the most up-to-date and detailed information about the trial.
What is NCT05950945 testing in simple terms?
This trial is testing a drug called trastuzumab deruxtecan (T-DXd) to see how well it works and how safe it is for advanced breast cancer. It is for patients with breast cancer that is considered HER2-low or HER2-negative, and has spread or cannot be removed by surgery.
Why is this trial significant?
This trial addresses a significant unmet need by investigating a promising targeted therapy for a large subgroup of breast cancer patients with limited treatment options. As a Phase 3 trial, positive results could lead directly to regulatory approval and new treatment options for patients.
What are the potential risks of participating in NCT05950945?
Common side effects may include nausea, fatigue, hair loss, and mouth sores. A serious but rare risk is lung inflammation (pneumonitis), which requires immediate medical attention. The drug can also affect heart function, so regular monitoring of your heart will be necessary. As with any clinical trial, participants are closely monitored and can withdraw at any time.
Should I consider participating in NCT05950945?
Ask your doctor if this trial is a good fit for you, considering your specific cancer type and treatment history. Participation involves regular clinic visits for IV infusions, scans to monitor your cancer, and blood tests to check your overall health. You will need to provide a recent tumor biopsy and potentially an archival sample for testing. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.
What does NCT05950945 signal from an investment perspective?
This trial targets a large and growing market for HER2-low breast cancer treatments, with T-DXd showing significant promise and potentially capturing a substantial market share. This is a Phase 3 trial, which is the final pivotal stage before potential regulatory submission.
What happens if the treatment in this trial doesn't work?
Participants will receive T-DXd through an IV drip every three weeks until their cancer progresses, they experience unacceptable side effects, or for up to two years. Participants in clinical trials always have the right to withdraw and pursue alternative treatments. The study team will help transition patients to other available options.
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This analysis is AI-generated and does not constitute medical advice. Always consult your healthcare provider before making decisions about clinical trial participation.