Data from HER2CLIMB-02 will be presented at an upcoming medical meeting and the results will be shared with the FDA.
The combination of tucatinib (Tukysa) and ado-trastuzumab emtansine (T-DM1; Kadcyla) has demonstrated improvement in progression-free survival (PFS) in patients with HER2-positive metastatic breast cancer (mBC), meeting the primary end point of the phase 3 HER2CLIMB-02 trial (NCT03975647).1
“We are encouraged by these results for Tukysa in combination with Kadcyla in metastatic HER2-positive breast cancer, including in patients with brain metastases,” said Roger Dansey, president of Research and Development and chief medical officer at Seagen, in a press release. “We plan to present the HER2CLIMB-02 data at an upcoming medical meeting and discuss the results with the FDA.”
Seagen, Inc also reported that overall survival (OS) data from HER2CLIMB-02 were immature at the time that PFS data were evaluated. Treatment discontinuations resulting from adverse events were more common with tucatinib plus T-DM1, but there were no new safety signals observed.
The rationale for the exploration of tucatinib plus T-DM1 in HER2CLIMB-02 comes for HER2CLIMB (NCT02614794), which led to the 2020 FDA approval of tucatinib in combination with trastuzumab and capecitabine for adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti–HER2-based regimens in the metastatic setting. In the study, the combination showed clinically meaningful survival benefit with a median overall survival (OS) of 24.7 months for the tucatinib combination compared with 19.2 months for placebo trastuzumab and capecitabine, according to final OS analysis results.2
The median PFS in HER2CLIMB was 7.6 months (95% CI, 6.9-8.3 months) with tucatinib vs 4.9 months (95% CI, 4.1-5.6 months) with placebo (HR, 0.57, 95% CI, 0.47-0.70, P <.00001). The tucatinib combination was also well-tolerated in the study.2 HER2CLIMB investigators deemed the combination to be an important treatment option for HER2-positive mBC, but HER2CLIMB-02 investigators believe more is needed for this population, including for those with brain metastases.2,3
HER2CLIMB-02 is a randomized, double-blind, phase 3 study comparing tucatinib plus T-DM1 to placebo plus T-DM1 in 565 patients. Patients will be randomized 1:1 to receive tucatinib 300 mg twice daily with T-DM1 at 3.6 mg/kg intravenously every 21 days or matching placebo plus T-DM1. Patients in the study will be evaluated every 6 weeks for the first 24 weeks of treatment to monitor disease progression followed by every 9 weeks. All patients will continue treatment until unacceptable toxicity, disease progression, withdrawal of consent, or closure of the study.
In addition to PFS, the study is investigating overall survival, objective responses, duration of response, clinical benefit rate, and the number of patients with adverse event (AEs) as secondary end points.
Patients eligible for treatment in the study are those with histologically confirmed HER2-positive mBC, history of prior treatment with a taxane, and trastuzumab in any setting, measurable or non-measurable disease per RECIST v1.1, an ECOG performance status or 0 or 1, and for central nervous system inclusion, patient must have no evidence of brain metastases, untreated brain metastases, or brain metastases that were previously treated.
The study excludes patients who have been previously treated with tucatinib, afatinib (Gilotrif) trastuzumab deruxtecan (DS-8201a), or another investigational anti-HER2 therapy, anti-EGFR therapy, or HER2 tyrosine kinase inhibitor, and those with certain CNS conditions.
1. Seagen phase 3 trial of Tukysa® (tucatinib) in combination with antibody-drug conjugate ado-trastuzumab emtansine meets primary endpoint of progression-free survival in patients with previously treated HER2-positive metastatic breast cancer. News release. Seagen Inc. August 16, 2023. Accessed August 16, 2023. https://tinyurl.com/4eaf9964
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. doi: 10.1016/j.annonc.2021.12.005
3. Hurvitz SA, Vahdat LT, Harbeck N, et al. 353TiP HER2CLIMB-02: A randomized, double-blind, phase III study of tucatinib or placebo with T-DM1 for unresectable locally advanced or metastatic HER2+ breast cancer. Ann Oncol. 2020; 31(4): S390. doi: 10.1016/j.annonc.2020.08.455