Unresectable locally-advanced or metastatic HER2+ breast cancer MedDRA version: 23.0 Level: PT Classification code 10065430 Term: HER2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10072740 Term: Locally advanced breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classificat
Conditions
Interventions
Trade Name: TUKYSA
Product Name: Tucatinib
Product Code: ONT-380
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Tucatinib
CAS Number: 1429755-56-5
Concentration unit: mg milligram(s)
Con
Sponsors
Seagen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have centrally confirmed HER2+ breast carcinoma per 2018 American Society of Clinical Oncologists (ASCO)-College of American Pathologists (CAP) guidelines. 2. Have unresectable locally advanced or metastatic (hereafter referred to as “advanced”) disease; if recurrent (after [neo]adjuvant therapy), there must be a minimum 6-month treatment-free interval from any trastuzumab or pertuzumab received in the early breast cancer setting to the diagnosis of advanced HER2+ disease. Prior standard of care therapy for early breast cancer is permitted (eg, prior T-DM1); however, Exclusion Criterion 1 should be noted. 3. Have received 4-8 cycles (21-day cycles) of previous treatment with trastuzumab, pertuzumab, and taxane as first-line therapy for advanced HER2+ breast cancer with no evidence of disease progression (per investigator judgement) a. Subjects receiving <6 cycles (ie, 4-5 cycles) of taxane are only eligible if the taxane was stopped early due to intolerable toxicity (eg, documented neuropathy impacting function). b. Subjects are permitted to receive trastuzumab and pertuzumab for 1 additional cycle (after completion of chemotherapy) during screening to allow completion of screening procedures. Study treatment should begin within 6 weeks (± 3 days) from the start of the last cycle of trastuzumab and pertuzumab. c. Subjects newly found to have asymptomatic brain metastasis during screening and treated with local CNS-directed therapy are permitted to receive trastuzumab and pertuzumab for up to 2 additional cycles (after completion of chemotherapy) to allow for the mandatory washout period. Study treatment should begin within 9 weeks (± 3 days) from the start of the last cycle of trastuzumab and pertuzumab. 4. Known hormone receptor status (per local guidelines; may be hormone receptor positive [HR+] or negative [HR-]) 5. Be at least 18 years of age, and legally an adult at time of consent and = the age of majority per regional requirements 6. Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 7. Have adequate hepatic function as defined in the protocol 8. Have adequate baseline hematologic parameters as defined in the protocol 9. Have a serum or plasma creatinine =1.5 X institutional ULN. 10. Have left ventricular ejection fraction (LVEF) =50% as assessed by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) documented within 4 weeks prior to first dose of study treatment. 11. Subjects of childbearing potential must meet the conditions as per protocol 12. Male subjects must meet the conditions as per protocol 13. Provide signed informed consent per a consent document that has been approved by an institutional review board or independent ethics committee (IRB/IEC) prior to initiation of any study-related tests or procedures that are not part of standard-of-care for the subject’s disease 14. Be willing and able to comply with study procedures 15. CNS Inclusion – Based on screening contrast brain magnetic resonance imaging (MRI), subjects may have any of the following: a. No evidence of brain metastases b. Untreated brain metastases which are asymptomatic and, if identified on prior brain imaging, without evidence of progression since starting first-line induction therapy with trastuzumab, pertuzumab, and taxane c. Previously treated brain metastases which are asymptomatic i. Brain metastases previously treated with local therapy must not have progressed since treatment a. Time since whole brain r
Exclusion criteria
Exclusion criteria: 1. Have previously been treated with any anti-HER2 and/or anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor including pyrotinib, lapatinib, tucatinib, neratinib, and afatinib (except neratinib if given in extended adjuvant setting and at least 12 months have elapsed from the last neratinib dose to the start of study drug) or are currently participating in another interventional clinical trial 2. Unable for any reason to undergo contrast MRI of the brain 3. History of allergic reactions to trastuzumab, pertuzumab, or compounds chemically or biologically similar to tucatinib, except for Grade 1 or 2 infusion-related reactions (IRRs) to trastuzumab that were successfully managed, known allergy to one of the excipients in the study drugs, or hypersensitivity to murine proteins 4. Are positive for Hepatitis B by surface antigen expression, positive for Hepatitis C infection, or the presence of known chronic liver disease. Subjects who have been treated for Hepatitis C infection are permitted if they have documented sustained virologic response of at least 12 weeks. The latest local guidelines should be followed regarding the testing of Hepatitis B DNA levels by polymerase chain reaction (PCR). Subjects with Hepatitis B DNA levels by PCR that require nucleoside analogue or other therapies are not eligible for the trial. 5. Subjects known to be positive for human immunodeficiency virus (HIV) are excluded if they meet any of the following criteria: a. CD4+ T-cell count of 2 mg of dexamethasone (or equivalent). For subjects requiring systemic steroids for control of comorbidities (eg, asthma or autoimmune diseases), daily dose must not exceed 2 mg dexamethasone (or equivalent). d. Any untreated brain lesion in an anatomic site which may pose risk to subject (eg, brain stem lesions). Subjects who successfully undergo l
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Compare progression-free survival (PFS) by investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 between treatment arms;Secondary Objective: - Compare overall survival (OS) between treatment arms - Evaluate PFS by blinded independent central review (BICR) per RECIST v1.1 - Assess the change in health-related quality of life (HRQoL) - Evaluate PFS in the brain - Evaluate the safety and tolerability of tucatinib in combination with trastuzumab and pertuzumab - Evaluate the pharmacokinetics (PK) of tucatinib;Primary end point(s): PFS per RECIST v1.1 according to investigator assessment, or death from any cause, whichever occurs first;Timepoint(s) of evaluation of this end point: Once approximately 331 PFS events per investigator assessment have been observed | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - OS - PFS per RECIST v1.1, as determined by BICR, or death from any cause, whichever occurs first - Time to deterioration of HRQoL - CNS-PFS per RECIST v1.1 according to investigator assessment, or death from any cause, whichever occurs first - AEs, clinical laboratory assessments, incidence of dose holding and discontinuation of study treatment, incidence of dose reductions of tucatinib - Plasma concentrations of tucatinib;Timepoint(s) of evaluation of this end point: - OS: final analysis will occur when approximately 252 OS events are observed - PFS by BICR: once approx. 331 PFS events have occurred - HRQoL: to be assessed on Day 1 of each 21-day cycle, at the end of treatment visit, and first follow-up visit - CNS-PFS: once approx. 331 PFS events have occurred - Safety assessments will be collected throughout the study. The safety reporting period for all AEs and SAEs is from study Cycle 1 Day 1 (predose) through 30 days after the last study treatment. - samples for PK assessment of tucatinib drug levels will be collected on Day 1 of Cycles 2 to 6 | — |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, Italy, Japan, Korea, Republic of, Poland, Portugal, Russian Federation, Spain, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactSeagen Clinical Trial Information
Seagen Inc.
Outcome results
None listed