A Randomized, Double-blind, Phase 3 Study of Tucatinib or Placebo in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy for Metastatic HER2+ Breast Cancer (HER2CLIMB-05)
Study tests tucatinib with standard drugs for advanced HER2+ breast cancer
Plain English Summary
A Study of Tucatinib or Placebo With Trastuzumab and Pertuzumab for Metastatic HER2+ Breast Cancer is a Phase 3 clinical trial sponsored by Seagen, a wholly owned subsidiary of Pfizer studying HER2 Positive Breast Cancer. This trial is testing if adding tucatinib to trastuzumab and pertuzumab is more effective than a placebo (inactive pill) for treating HER2-positive breast cancer that has spread. It is for patients with HER2-positive breast cancer that has spread and cannot be removed, and who have already received a specific initial treatment. Participants will receive either tucatinib or a placebo, along with trastuzumab and pertuzumab, in a blinded manner, meaning neither patients nor doctors will know who is receiving the active drug. Alternative treatments for this condition include other chemotherapy drugs, targeted therapies, and hormone therapy, depending on the specific characteristics of the cancer. The trial aims to enroll 654 participants.
Official Summary
This study is being done to see if tucatinib works better than placebo when given with other drugs to treat participants with HER2-positive breast cancer. A placebo is a pill that looks the same as tucatinib but has no medicine in it. This study will also test what side effects happen when participants take this combination of drugs. A side effect is anything a drug does to the body besides treating your disease. Participants will have cancer that has spread in the body near where it started (locally advanced) and cannot be removed (unresectable) or has spread through the body (metastatic). In this study, all participants will get either tucatinib or placebo. Participants will be assigned randomly to a group. This is a blinded study, so patients and their doctors will not know which group a participant is in. All participants will also get trastuzumab and pertuzumab. These are 2 drugs used to treat this type of cancer.
Who Can Participate
Here is what you need to know about eligibility for this trial. Patients with HER2-positive breast cancer that has spread (locally advanced or metastatic) and cannot be surgically removed can join. Patients must have completed a specific first-line treatment (trastuzumab, pertuzumab, and taxane) and have not had their cancer progress. Patients must be between 18 and 75 years old and have a good general health status (ECOG 0 or 1). Patients with brain metastases are eligible if they are asymptomatic and stable, or have been previously treated and are asymptomatic. This trial is studying HER2 Positive Breast Cancer, so participants generally need a confirmed diagnosis.
What They're Measuring
Progression-free survival means the study will measure how long patients live without their cancer getting worse, which is a key indicator of treatment effectiveness. The specific primary outcome measures are: Progression-free survival (PFS) by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Up to approximately 3 years). 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 need for more effective maintenance therapies in HER2-positive metastatic breast cancer, aiming to improve outcomes for patients whose cancer has spread. 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 HER2 Positive Breast Cancer, where improved treatment options are needed.
Investor Insight
This trial, sponsored by Seagen (a Pfizer subsidiary), targets a significant market for HER2+ breast cancer treatments, with a strong competitive landscape and a potentially high probability of approv Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 654 participants suggests significant investment in this program.
Is This Trial Right for Me?
Ask your doctor about the specific eligibility requirements and what it means to be in a blinded study. Understand that participation involves regular clinic visits for drug administration, monitoring, and tests. Be prepared for potential side effects and the need for regular imaging to check for cancer progression. 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: RANDOMIZED
- Model: PARALLEL
- Masking: QUADRUPLE
- Enrollment: 654 participants
Interventions
- DRUG: Tucatinib — 300mg given by mouth (orally) twice daily
- DRUG: Trastuzumab — 6mg/kg given into the vein (IV; intravenously) or 600mg injected under the skin (SC; subcutaneous) every 21 days
- DRUG: Pertuzumab — 420mg given by IV every 21 days
- DRUG: Combination product: Trastuzumab + Pertuzumab — 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase will be given by subcutaneous injection every 21 days. May be given in place of trastuzumab and pertuzumab individually.
- DRUG: Placebo — Given orally twice daily
Primary Outcomes
- Progression-free survival (PFS) by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Up to approximately 3 years)
Secondary Outcomes
- Overall survival (OS) (Up to approximately 5 years)
- PFS by blinded independent central review (BICR) per RECIST v1.1 (Up to approximately 3 years)
- Time to deterioration of health-related quality of life (HRQoL) (Up to approximately 3 years)
- Central nervous system (CNS) PFS (Up to approximately 3 years)
- Incidence of adverse events (AEs) (Through 30 days after last study treatment, approximately 18 months)
Full Eligibility Criteria
Inclusion Criteria:
* Centrally confirmed HER2+ breast carcinoma according to the 2018 American Society of Clinical Oncologists (ASCO) College of American Pathologists (CAP) guidelines prior to randomization (defined as a 3+ score on immunohistochemistry (IHC) and/or 2+ IHC and concurrent positive by ISH).
* Have unresectable locally advanced or metastatic disease.
* If recurrent (after \[neo\]adjuvant therapy), must be at least 6 month treatment free from any trastuzumab and pertuzumab received in the early breast cancer setting for advanced HER2+ disease.
* Have received 4-8 cycles of pre-study induction therapy including only trastuzumab, pertuzumab, and taxane as first-line of therapy for the treatment of advanced breast cancer prior to study enrollment. Participants are eligible provided they are without evidence of disease progression following completion of induction therapy.
* Known hormone receptor status (per local guidelines; may be hormone receptor positive \[HR+\] or negative \[HR-\])
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* CNS Inclusion - Based on screening contrast-enhanced brain magnetic resonance imaging (MRI), participants may have any of the following:
* No evidence of brain metastases
* Untreated brain metastases which are asymptomatic not needing immediate local treatment and, if identified on prior brain imaging, without evidence of progression since starting first-line induction therapy with trastuzumab, pertuzumab, and taxane
* Previously treated brain metastases which are asymptomatic
* Brain metastases previously treated with local therapy must not have progressed since treatment
Exclusion Criteria:
* Prior treatment with any tyrosine kinase inhibitor targeting HER2 and/or epidermal growth factor receptor (EGFR) including pyrotinib, lapatinib, tucatinib, neratinib, and afatinib (except neratinib if given in extended adjuvant setting and ≥ 12 months have elapsed since last neratinib dose prior to start of study drug)
* Unable to undergo contrast-enhanced MRI of the brain
* CNS Exclusion - Based on screening brain MRI and clinical assessment
* Symptomatic brain metastasis after CNS-directed local therapy
* Progression of brain metastases since starting first line trastuzumab, pertuzumab, and taxane
* Ongoing use of systemic corticosteroids at a total daily dose of \>2 mg of dexamethasone (or equivalent)
* Any untreated brain lesion in an anatomic site which may pose risk to participant
* Known or suspected leptomeningeal disease (LMD)
* Poorly controlled (\>1/week) seizures, or other persistent neurologic symptomsTrial Locations
- Mayo Clinic Hospital, Phoenix, Arizona, United States
- Mayo Clinic, Scottsdale, Arizona, United States
- Central Arkansas Radiation Therapy Institute Inc d.b.a CARTI, Little Rock, Arkansas, United States
- UCLA Hematology/Oncology - Beverly Hills, Beverly Hills, California, United States
- UCLA Hematology/Oncology - Burbank, Burbank, California, United States
- UCSD Medical Center - Encinitas, Encinitas, California, United States
- Sulpizio Cardiovascular Center at UC San Diego Health, La Jolla, California, United States
- UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion), La Jolla, California, United States
- UCSD Koman Family Outpatient Pavilion, La Jolla, California, United States
- UCSD Perlman Medical Offices, La Jolla, California, United States
- ...and 10 more locations
Frequently Asked Questions
What is clinical trial NCT05132582?
NCT05132582 is a Phase 3 INTERVENTIONAL study titled "A Study of Tucatinib or Placebo With Trastuzumab and Pertuzumab for Metastatic HER2+ Breast Cancer." It is currently active, not recruiting and is sponsored by Seagen, a wholly owned subsidiary of Pfizer. The trial targets enrollment of 654 participants.
What conditions does NCT05132582 study?
This trial investigates treatments for HER2 Positive Breast Cancer. The primary condition under study is HER2 Positive Breast Cancer.
What treatments are being tested in NCT05132582?
The interventions being studied include: Tucatinib (DRUG), Trastuzumab (DRUG), Pertuzumab (DRUG), Combination product: Trastuzumab + Pertuzumab (DRUG), Placebo (DRUG). 300mg given by mouth (orally) twice daily
What does Phase 3 mean for NCT05132582?
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 NCT05132582?
This trial is currently "Active, Not Recruiting." It started on 2022-03-07. The estimated completion date is 2027-09-28.
Who is sponsoring NCT05132582?
NCT05132582 is sponsored by Seagen, a wholly owned subsidiary of Pfizer. The sponsor is responsible for funding, designing, and overseeing the clinical trial.
How many people can participate in NCT05132582?
The trial aims to enroll 654 participants. The trial status is active, not recruiting.
How is NCT05132582 designed?
This is a interventional study, uses randomized allocation, follows a parallel design, employs quadruple masking. Masking means some participants and/or investigators do not know which treatment group a participant is in, which helps reduce bias.
What are the primary outcomes being measured in NCT05132582?
The primary outcome measures are: Progression-free survival (PFS) by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Up to approximately 3 years). These are the main endpoints researchers use to determine whether the treatment is effective.
Where is NCT05132582 being conducted?
This trial is being conducted at 20 sites, including Phoenix, Arizona; Scottsdale, Arizona; Little Rock, Arkansas; Beverly Hills, California and 16 more sites (United States).
Where can I find official information about NCT05132582?
The official record for NCT05132582 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT05132582. This government database provides the most up-to-date and detailed information about the trial.
What is NCT05132582 testing in simple terms?
This trial is testing if adding tucatinib to trastuzumab and pertuzumab is more effective than a placebo (inactive pill) for treating HER2-positive breast cancer that has spread. It is for patients with HER2-positive breast cancer that has spread and cannot be removed, and who have already received a specific initial treatment.
Why is this trial significant?
This trial addresses a significant need for more effective maintenance therapies in HER2-positive metastatic breast cancer, aiming to improve outcomes for patients whose cancer has spread. 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 NCT05132582?
Common side effects may include diarrhea, nausea, fatigue, and skin rash. There is a risk of liver problems, and for patients with brain metastases, there's a possibility of worsening neurological symptoms. Specific to tucatinib, potential side effects include increased liver enzymes and diarrhea. As with any clinical trial, participants are closely monitored and can withdraw at any time.
Should I consider participating in NCT05132582?
Ask your doctor about the specific eligibility requirements and what it means to be in a blinded study. Understand that participation involves regular clinic visits for drug administration, monitoring, and tests. Be prepared for potential side effects and the need for regular imaging to check for cancer progression. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.
What does NCT05132582 signal from an investment perspective?
This trial, sponsored by Seagen (a Pfizer subsidiary), targets a significant market for HER2+ breast cancer treatments, with a strong competitive landscape and a potentially high probability of approv 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 either tucatinib or a placebo, along with trastuzumab and pertuzumab, in a blinded manner, meaning neither patients nor doctors will know who is receiving the active drug. 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.