Trial in Progress: Phase 3 HER2CLIMB-05 Study of Tucatinib or Placebo Plus Trastuzumab and Pertuzumab as Maintenance Therapy for HER2+ MBC

Trastuzumab plus pertuzumab and a taxane is the current standard-of-care induction therapy for HER2+ metastatic breast cancer (MBC); however, the majority of patients progress during maintenance therapy with trastuzumab plus pertuzumab. Results of the HER2CLIMB study demonstrated that the addition of the tyrosine kinase inhibitor (TKI) tucatinib to trastuzumab plus capecitabine significantly prolonged progression-free survival (PFS) and overall survival (OS) in patients with HER2+ MBC, including those with untreated and/or active brain metastasis.1,2 Based on these results, it was hypothesized that the addition of tucatinib to trastuzumab plus pertuzumab maintenance therapy may provide survival benefit without compromising quality of life. The HER2CLIMB-05 (NCT05132582) trial was initiated to evaluate the efficacy and safety of the addition of tucatinib to trastuzumab plus pertuzumab as maintenance therapy for HER2+ MBC.

The HER2CLIMB-05 trial will enroll patients with centrally confirmed advanced (unresectable locally advanced or metastatic disease) HER2+ breast carcinoma, no progression on 4 to 8 cycles of prior first-line standard of care, Eastern Cooperative Oncology Group performance status of 0 or 1, and no or asymptomatic brain metastasis. Exclusion criteria include prior treatment with anti-HER2 and/or anti-epidermal growth factor receptor TKI for metastatic disease or inability to undergo brain contrast magnetic resonance imaging. Eligible patients will be randomized 1:1 to receive either tucatinib (300 mg) or placebo twice daily with trastuzumab (6 mg/kg IV or 600 mg SC) plus pertuzumab (420 mg/kg IV) once every 21 days. Patients with HR+ tumors may receive endocrine therapy.

The primary end point is investigator-assessed PFS; secondary end points include OS, PFS by blinded independent committee review (BICR), central nervous system-PFS by investigator, time to deterioration of health-related quality of life, safety, and pharmacokinetic parameters.

Approximately 650 patients will be enrolled. Enrollment is ongoing in the US, Canada, LATAM, APAC, and European countries with additional sites planned.

Source:

Hamilton E, Tsurutani J, Curigliano G, et al. Phase 3 study of tucatinib or placebo in combination with trastuzumab and pertuzumab as maintenance therapy for HER2+ metastatic breast cancer (HER2CLIMB-05, Trial in Progress). Presented at the 46th San Antonio Breast Cancer Symposium Annual Meeting, December 5-9, 2023; San Antonio, TX: Abstract PO1-19-11.

1. Murthy RK, Loi S, Okines A, et al. tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382(7):597-609.
2. Curigliano G, Mueller V, Borges V, et al. Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis. Ann Oncol. 2022;33(3):321-329.