for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion:
Amy Chien



To assess the effect of tucatinib vs. placebo in combination with capecitabine and trastuzumab on progression-free survival (PFS) per RECIST 1.1 based on independent central radiology review.

Official Title

Phase 2 Randomized, Double-Blinded, Controlled Study of Tucatinib vs Placebo in Combination With Capecitabine and Trastuzumab in Patients With Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Carcinoma (HER2CLIMB)


A randomized, international, multi-center, double-blinded study in patients with progressive unresectable locally advanced or metastatic HER2+ breast cancer who have had prior treatment with trastuzumab, pertuzumab and T-DM1. Patients will be randomized in a 2:1 ratio to receive tucatinib or placebo in combination with capecitabine and trastuzumab.

Stratification factors include presence or history of treated or untreated brain metastases (yes/no), Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0 vs. 1), and region of world (US vs Canada vs Rest of World).

No crossover from placebo to tucatinib will be allowed.

Safety assessments will be performed at a minimum of once every three weeks throughout study treatment and 30 days after the last dose of study drugs. Laboratory assessments will be performed locally at sites. Left ventricular ejection fraction will be assessed by MUGA or ECHO at screening and once every 12 weeks thereafter.

Contrast brain MRI will be performed at baseline in all patients. Efficacy assessments (CT of chest, abdomen and pelvis at a minimum) utilize RECIST 1.1 and include patients with evaluable tumors defined as measurable target lesions and non-measurable non-target lesions. RECIST assessment is performed at baseline, every 6 weeks for the first 24 weeks, and then every 9 weeks thereafter. Repeat MRI of the brain will be required on this same schedule only in those patients with brain metastases identified at baseline. All treatment decisions are made based upon investigator assessment. All patients undergo a repeat MRI of the brain within 30 days of the end of treatment unless previously performed at time of disease progression. Patients in both arms of the study will be followed for OS after completion of study treatment.


HER2 Positive Breast Cancer Tucatinib Capecitabine Trastuzumab Xeloda Herceptin Breast Cancer ARRY-380 ONT-380 HER2 Positive Breast Carcinoma HER2 Positive Locally Advanced Breast Cancer HER-2 Positive Breast Cancer HER-2 Positive Breast Carcinoma HER-2 Positive Locally Advanced Breast Cancer Recurrent Breast Carcinoma Stage IV Breast Cancer Metastatic Breast Cancer Breast Carcinoma Metastatic Malignant Neoplasm in the Brain Brain Metastases in Breast Cancer Asymptomatic Brain Metastases in Breast Cancer Low Symptomatic Brain Metastases in Breast Cancer Breast Neoplasms


You can join if…

Open to people ages 18 years and up

Histologically confirmed HER2+ breast carcinoma, with HER2+ defined by in situ hybridization (ISH) or fluorescence in situ hybridization (FISH) methodology

Received previous treatment with trastuzumab, pertuzumab, and T-DM1

Progression of unresectable locally advanced or metastatic breast cancer after last systemic therapy (as confirmed by investigator), or be intolerant of last systemic therapy

Have measurable or non-measurable disease assessable by RECIST 1.1

At least 18 years of age at time of consent

Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1

Adequate hepatic and renal function

Left ventricular ejection fraction (LVEF) ≥ 50%

CNS Inclusion - Based on screening brain magnetic resonance imaging (MRI), patients must have one of the following:

  • No evidence of brain metastases
  • Untreated brain metastases not needing immediate local therapy
  • Previously treated brain metastases not needing immediate local therapy
  • Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy
  • Patients treated with CNS local therapy for newly identified lesions found on contrast brain MRI performed during screening for this study may be eligible to enroll if the following criteria are met:
  • Time since whole brain radiation therapy (WBRT) is ≥ 21 days prior to first dose of study treatment, time since stereotactic radiosurgery (SRS) is ≥ 7 days prior to first dose of study treatment, or time since surgical resection is ≥ 28 days.

ii. Other sites of evaluable disease are present

  1. Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions

You CAN'T join if...

Previously been treated with:

  1. lapatinib within 12 months of starting study treatment (except in cases where lapatinib was given for ≤ 21 days and was discontinued for reasons other than disease progression or toxicity)
  2. neratinib, afatinib, or other investigational HER2/epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor (TKI) at any time previously
  3. previously been treated with capecitabine for metastatic disease except in cases where capecitabine was given for < 21 days and was discontinued for reasons other than disease progression or toxicity. Patients who have received capecitabine for adjuvant or neoadjuvant treatment at least 12 months prior to starting study treatment are eligible.

Clinically significant cardiopulmonary disease

Carriers of Hepatitis B or Hepatitis C or have other known chronic liver disease

Positive for human immunodeficiency virus (HIV)

Unable for any reason to undergo MRI of the brain

CNS Exclusion - Based on screening brain MRI, patients must not have any of the following:

Any untreated brain lesions > 2.0 cm in size, unless discussed with medical monitor

Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of > 2 mg of dexamethasone (or equivalent)

Any brain lesion thought to require immediate local therapy. Patients who undergo local treatment for such lesions identified by screening contrast brain MRI may still be eligible for the study based on criteria described under CNS inclusion criteria

Known or concurrent leptomeningeal disease (LMD)

Poorly controlled seizures


  • UCSF Medical Center - Helen Diller Family Comprehensive Cancer Center accepting new patients
    San Francisco California 94115 United States
  • Kaiser Permanente accepting new patients
    Vallejo California 94589 United States


accepting new patients
Start Date
Completion Date
Cascadian Therapeutics Inc.
Phase 2
Lead Scientist
Amy Chien
Study Type
Last Updated