Tucatinib

Unassigned

New Medicines

Locally advanced unresectable or metastatic HER2-positive breast cancer in patients previously treated with trastuzumab, pertuzumab and T-DM1 - with capecitabine and trastuzumab

Information

New molecular entity
Astellas
Seattle-Genetics

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Pre-registration (Filed)
Yes
Feb 20 · The EMA has validated the MAA for tucatinib in combination with trastuzumab and capecitabine, for the treatment of adult patients with locally advanced unresectable or metastatic HER2-positive breast cancer [10].
Jan 20 · In its latest quarterly report, Seattle states that Astellas has commercialisation rights in rest of the world, including Europe. The agreement is intended to provide that Seattle and Astellas will effectively share equally in costs incurred and any profits realised in all of these markets. Cost and profit sharing in Canada, the United Kingdom, Germany, France, Spain and Italy will be based on product sales and costs of commercialisation [8].
Dec 19 · Seattle Genetics announces intention to submit MAA to European Medicines Agency (EMA) in Q1 20 [7].
Dec 19 · An NDA has been submitted to the FDA for tucatinib use in combination with trastuzumab and capecitabine for treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer who have received at least three prior HER2-directed agents separately or in combination, in the neoadjuvant, adjuvant or metastatic setting [6].
Oct 19 · Array Biopharma announce plans to submit NDA to FDA in Q1 2020.[3]
Jun 17 · US FDA grant orphan drug designation to tucatinib for treatment of breast cancer and brain metastasis. [4]

Category

Oral tyrosine kinase inhibitor selective for HER2 (ERBB-2 receptor) - prevents activation of ERBB-2 signal transduction pathways, and results in the growth inhibition and death of HER2/ERBB-2-expressing tumour cells.[3,4]
In the UK, it is estimated that there are ~55200 new cases of invasive breast cancer per year based on averages between 2014 and 2016.[1] Between 15-20% of cases are HER2+. [2,3]
Locally advanced unresectable or metastatic HER2-positive breast cancer in patients previously treated with trastuzumab, pertuzumab and T-DM1 - with capecitabine and trastuzumab
Oral

Trial or other data

Dec 19 · PII HER2CLIMB randomised 2:1, double-blind trial (NCT02614794) initiated to evaluate efficacy of oral tucatinib twice daily vs. placebo both with oral capecitabine (twice daily in the first 2 weeks of each cycle) and trastuzumab injection (once on the first day of each cycle). The trial enrolled ~480 pts globally with unresectable locally advanced or metastatic HER2+ breast cancer in pts with and without brain metastases, who have previously been treated with a taxane, trastuzumab, pertuzumab and trastuzumab-emtansine. The primary endpoint is progression-free survival (PFS) based upon independent radiologic review. The study expects to complete in H2 2021. [3-5]
Oct 19 · The HER2CLIMB trial enrolled 612 pts and met the primary endpoint of PFS showing that adding tucatinib was superior to trastuzumab and capecitabine alone. There was a 46% decrease in the risk of disease progression (HR=0.54, 95% CI: 0.42, 0.71, p<0.00001). and 52% decrease in pts with brain mets, p<0.00001). There was also improvement in overall survival (OS) with a 34% decrease in risk of death.(HR=0.66, 95% CI: 0.50, 0.88, p=0.0048). Tucatinib in combination with trastuzumab and capecitabine was generally well tolerated with a manageable safety profile. The most frequent adverse events in the tucatinib arm included diarrhea, increased AST and bilirubin levels, palmar-plantar erythrodysaesthesia syndrome (PPE), nausea, fatigue, and vomiting.[3]
Aug 19 · Pivotal PIII HER2CLIMB-02 randomised, double-blind trial (NCT03975647) initiated to assess the safety and efficacy of oral tucatinib or placebo pills twice daily with ado-trastuzumab emtansine injections on the first day of every 21 day cycle in ~460 pts with HER2+ breast cancer.[3-5]
Dec 15 · PII HER2CLIMB randomised 2:1, double-blind trial (NCT02614794) initiated to evaluate efficacy of oral tucatinib twice daily vs. placebo both with oral capecitabine (twice daily in the first 2 weeks of each cycle) and trastuzumab injection (once on the first day of each cycle). The trial enrolled ~480 pts globally with unresectable locally advanced or metastatic HER2+ breast cancer in pts with and without brain metastases, who have previously been treated with a taxane, trastuzumab, pertuzumab and trastuzumab-emtansine. The primary endpoint is progression-free survival (PFS) based upon independent radiologic review. The study expects to complete in H2 2021. [3-5]