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

JRCT ID: jRCT2011220007

Registered date:28/05/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: metastatic HER2+ breast cancer
• Date of first enrollment: 30/04/2022
• Target sample size: 47
• Countries of recruitment: USA,Japan,Canada,Japan,Italy,Japan,Spain,Japan,Germany,Japan,Austria,Japan,Switzerland,Japan,France,Japan,Poland,Japan,Portugal,Japan,United Kingdom,Japan,Belgium,Japan,China,Japan,Taiwan,Japan,Korea,Japan,Australia,Japan,Brazil,Japan,Chile,Japan,Czech Republic,Japan,Finland,Japan,Greece,Japan,Netherlands,Japan
• Study type: Interventional

Intervention(s)

Subjects will be randomized in a 1:1 ratio to receive 1 of the following study treatments, either:
1. Control arm: Placebo tablets PO BID plus trastuzumab and pertuzumab every 21 days
2. Experimental arm: Tucatinib 300 mg PO BID plus trastuzumab and pertuzumab every
21 days
Trastuzumab and pertuzumab will be administered as:
- Trastuzumab will be given IV at a dose of 6 mg/kg or SC at a fixed dose of 600 mg, once every 21 days.
AND
- Pertuzumab will be given IV at 420 mg every 21 days.
OR
Study SGNTUC-028 Clinical Protocol Amendment 01, 09-Aug-2021
Tucatinib Seagen Inc. - Confidential Page 39 of 103
- Fixed dose combination of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase will be given SC, once every 21 days, in lieu of trastuzumab and pertuzumab individually.

Outcome(s)

• Primary Outcome: Progression-free survival (PFS) by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

-Centrally confirmed HER2+ breast carcinoma per 2018 American Society of Clinical Oncologists (ASCO) College of American Pathologists (CAP) guidelines.
-Have unresectable locally advanced or metastatic disease.
- If recurrent (after [neo]adjuvant therapy), must be at least 6 month treatment free from any trastuzumab or pertuzumab received in the early breast cancer setting to the diagnosis of advanced HER2+ disease..
-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
-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 brain magnetic resonance imaging (MRI), participants may have any of the following:
- No evidence of brain metastases
- 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
- Previously treated brain metastases which are asymptomatic
* Brain metastases previously treated with local therapy must not have progressed since treatment"

Exclude criteria

-Prior treatment 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 >= 12 months have elapsed since last neratinib dose prior to start of study drug)
-Unable to undergo contrast MRI of the brain
-CNS Exclusion - Based on screening brain MRI and clinical assessment
-Symptomatic brain metastasis
-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 symptoms"

Related Information

• Primary Sponsor: Nakamura Yoshinobu
• Secondary ID(s): NCT05132582