Randomized, Double-blind, Phase 3 Study of Tucatinib or Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Subjects With Unresectable Locally-advanced or Metastatic HER2+ Breast Cancer (HER2CLIMB-02)

Plain English Summary

A Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or 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 tests if adding tucatinib to a standard treatment (T-DM1) helps patients with advanced HER2-positive breast cancer live longer without their cancer getting worse. It is for patients with HER2-positive breast cancer that has spread or cannot be fully removed by surgery, and who have already received certain prior treatments. Participants will receive either tucatinib or a placebo (inactive pill) along with T-DM1, and will not know which they are receiving. Treatment involves daily pills and regular IV infusions. Alternative treatments may include other chemotherapy, targeted therapies, or immunotherapy, depending on the patient's specific situation and prior treatments. The trial aims to enroll 466 participants.

Official Summary

This study is being done to see if tucatinib with ado-trastuzumab emtansine (T-DM1) works better than T-DM1 alone to help patients who have a specific type of breast cancer called HER2 positive breast carcinoma. The breast cancer in this study is either metastatic (spread into other parts of the body) or cannot be removed completely with surgery. Patients in this study will be randomly assigned to get either tucatinib or placebo (a pill with no medicine). This is a blinded study, so neither patients nor their doctors will know whether a patient gets tucatinib or placebo. All patients in the study will get T-DM1, a drug that is often used to treat this cancer. Each treatment cycle lasts 21 days. Patients will swallow tucatinib pills or placebo pills two times every day. Patients will get T-DM1 injections from the study site staff on the first day of every cycle.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with HER2-positive breast cancer that has spread or cannot be removed by surgery. Must have received prior treatment with a taxane and trastuzumab. Must have cancer progression or intolerance to their last treatment. Patients with brain metastases may be eligible if they have been treated and are stable or have other measurable disease. This trial is studying HER2-positive Breast Cancer, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how long patients live without their cancer getting worse, which means it aims to extend the time patients can live without their disease progressing. The specific primary outcome measures are: Progression-Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 Based on Investigator Assessment (From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 43 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 critical need for more effective treatments for advanced HER2-positive breast cancer, particularly for patients whose cancer has spread or returned after initial therapies. 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 is sponsored by Seagen (Pfizer), a major player in oncology, indicating a strong commercial interest in developing new treatments for a significant market of HER2+ breast cancer patients, w 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 and treatment history. Be prepared for daily oral medication (tucatinib or placebo) and regular IV infusions of T-DM1 at a study site. Understand that you and your doctor will not know if you are receiving the active drug (tucatinib) or a placebo. 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: 466 participants

Interventions

• DRUG: tucatinib — 300mg given twice per day by mouth (orally)
• DRUG: placebo — Given twice per day orally
• DRUG: T-DM1 — 3.6 mg/kg given into the vein (IV; intravenously) every 21 days

Primary Outcomes

• Progression-Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 Based on Investigator Assessment (From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 43 months))

Secondary Outcomes

• Overall Survival (OS) (Up to approximately 5 years)
• Progression-Free Survival as Per RECIST v1.1 in Participants With Brain Metastases at Baseline Based on Investigator Assessment (From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 45 months))
• Objective Response Rate (ORR) as Per RECIST v1.1 Based on Investigator Assessment (From the date of first CR or PR until the date of the first documentation of PD or death, whichever occurred first (maximum up to 43 months))
• Overall Survival in Participants With Brain Metastases at Baseline (Up to approximately 5 years)
• Progression-Free Survival as Per RECIST v1.1 Determined by Blinded Independent Committee Review (BICR) (From the date of randomization to the date of PD or death from any cause or censoring date, whichever occurred first (maximum up to 43 months))

Full Eligibility Criteria

* Inclusion Criteria:

  * Histologically confirmed HER2+ breast carcinoma as determined by a sponsor-designated central laboratory
  * History of prior treatment with a taxane and trastuzumab in any setting, separately or in combination
  * Have progression of unresectable locally advanced/metastatic breast cancer after last systemic therapy, or be intolerant of last systemic therapy
  * Measurable or non-measurable disease assessable by RECIST v1.1
  * ECOG performance status score of 0 or 1
  * CNS Inclusion - Based on screening contrast brain magnetic resonance imaging (MRI), participants must have at least one of the following:

    (a) No evidence of brain metastases

    (b) Untreated brain metastases not needing immediate local therapy

    (c) Previously treated brain metastases
    1. Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy
    2. Participants treated with CNS local therapy for newly identified lesions or previously treated and progressing lesions may be eligible to enroll if all of the following criteria are met:

       (i) Time since SRS is at least 7 days prior to first dose of study treatment, time since WBRT is at least 14 days prior to first dose, or time since surgical resection is at least 28 days.

       (ii) Other sites of evaluable disease are present
    3. Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions
* Exclusion Criteria:

  * Prior treatment with tucatinib, afatinib, trastuzumab deruxtecan (DS-8201a), or any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent. Prior treatment with lapatinib or neratinib within 12 months of starting study treatment (except in cases where they were given for ≤21 days and was discontinued for reasons other than disease progression or severe toxicity). Prior treatment with pyrotinib for recurrent of mBC (except in cases where pyrotinib was given for ≤21 days and was discontinued for reasons other than disease progression or severe toxicity).
  * CNS Exclusion - Based on screening contrast brain magnetic resonance imaging (MRI), participants must not have any of the following:

    1. Any untreated brain lesions \>2 cm in size
    2. Ongoing use of corticosteroids for control of symptoms of brain metastases at a total daily dose of \>2 mg of dexamethasone (or equivalent).
    3. Any brain lesion thought to require immediate local therapy
    4. Known or concurrent leptomeningeal disease as documented by the investigator
    5. Poorly controlled generalized or complex partial seizures

Trial Locations

• University of South Alabama Health Children's and Women's Hospital, Mobile, Alabama, United States
• University of South Alabama Mitchell Cancer Institute, Mobile, Alabama, United States
• University of South Alabama Health University Hospital, Mobile, Alabama, United States
• Banner Gateway Medical Center, Gilbert, Arizona, United States
• Banner MD Anderson Cancer Center, Gilbert, Arizona, United States
• Western Regional Medical Center, LLC, Goodyear, Arizona, United States
• Arizona Oncology Associates, PC - HOPE., Tucson, Arizona, United States
• Arizona Oncology Associates, PC - HOPE, Tucson, Arizona, United States
• Arizona Oncology Associates, PC - HOPE, Tucson, Arizona, United States
• UCLA Hematology/Oncology - Alhambra, Alhambra, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Breast Cancer
• HER2-positive Breast Cancer
• Metastatic Breast Cancer
• Locally Advanced Breast Cancer
• HER2-positive Solid Tumors
• Oncology
• Targeted Therapy
• Chemotherapy
• Cancer
• Malignant Neoplasm

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