HER2CLIMB-05: Phase 3 Study of Tucatinib or Placebo in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy for HER2-Positive LA/MBC

Dual HER2 inhibition with trastuzumab plus pertuzumab (TP) combined with a taxane is the current first-line (1L) standard of care (SOC) in patients with HER2-positive metastatic breast cancer (MBC); however, the majority of patients progress during TP maintenance therapy. The tyrosine kinase inhibitor (TKI) tucatinib, in combination with trastuzumab and capecitabine, previously demonstrated clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS), with a tolerable safety profile, in patients with HER2-positive MBC. The ongoing HER2CLIMB-05 (NCT05132582) trial investigates whether the addition of tucatinib to TP as maintenance therapy will provide a survival advantage while maintaining quality of life (QOL) in patients with HER2-positive unresectable locally advanced or MBC (LA/MBC) following SOC induction therapy.

Inclusion criteria include patients with HER2-positive unresectable LA/MBC, no progression on 4 to 8 cycles of prior 1L SOC, known hormone receptor status, Eastern Cooperative Oncology Group Performance Status of 0 or 1, and absence of or asymptomatic brain metastasis. Exclusion criteria include prior treatment with any HER2- and/or epidermal growth factor receptor–targeting TKIs; however, prior treatment with neratinib in the extended adjuvant setting (with ≥12 months elapsing since the last dose) is permitted.

Eligible patients will be randomly assigned 1:1 to receive either tucatinib or placebo twice daily and TP once every 21 days. Patients with hormone receptor–positive disease may receive endocrine therapy according to institutional SOC. The primary end point is investigator-assessed PFS. Secondary end points include OS, PFS by blinded independent central review, time to deterioration of health-related QOL, central nervous system PFS, safety, and pharmacokinetic parameters.

It is planned that the study will enroll approximately 650 patients. Enrollment is ongoing in the United States, Canada, Brazil, Asia-Pacific, and European Union countries with additional sites planned.

Source:

Hamilton EP, Martin M, O’Sullivan CC, et al. HER2CLIMB-05: phase 3 study of tucatinib or placebo in combination with trastuzumab and pertuzumab as maintenance therapy for HER2+ metastatic breast cancer. Abstract presented at: ASCO Annual Meeting, June 2-6, 2023; Chicago, IL. Abstract TPS1115.