SEAGEN INC. The combination showed a statistically significant improvement in progression-free survival (PFS), the study's primary endpoint, in patients with unresectable locally advanced or metastatic human epidermal growth factor receptor 2-positive (HER2-positive) breast cancer who had been previously treated with trastuzumab and a taxane, compared to those who received placebo plus ado-trastuzumab emtansine. Discontinuations due to adverse events were more common in the combination arm of the trial, but no new safety signals were observed for the combination.
'Combining HER2-directed therapies can improve outcomes for people with locally advanced or metastatic HER2-positive breast cancer,' said lead author
'The results from the HER2CLIMB-02 study reinforce the clinical activity of TUKYSA in patients with HER2-positive metastatic breast cancer,' said
Patients who received TUKYSA in combination with ado-trastuzumab emtansine experienced: Median PFS of 9.5 months (95% Confidence Interval [CI]: 7.4, 10.9) by investigator assessment per RECIST v1.1 compared to 7.4 months (95% CI: 5.6, 8.1) in the placebo plus ado-trastuzumab emtansine arm (Hazard Ratio [HR], 0.76 [95% CI: 0.61, 0.95); P=0.0163).
In patients with brain metastases, median PFS of 7.8 months (95% CI: 6.7, 10.0) compared to 5.7 months (95% CI: 4.6, 7.5) in the placebo arm (HR, 0.64 [95% CI: 0.46, 0.89]).
Confirmed objective response rate (cORR) of 42.0% versus 36.1% in the placebo arm.
Overall survival (OS) data, a secondary endpoint, are not yet mature.
The most common (5%) Grade 3 or higher adverse events (AEs) were alanine transferase (ALT) increase (16.5% versus 2.6%), aspartate transferase (AST) increase (16.5% versus 2.6%), anemia (8.2% versus 4.7%), thrombocytopenia (7.4% versus 2.1%), and fatigue (6.1% versus 3.0%).
TUKYSA in combination with trastuzumab and capecitabine is approved by the
About HER2CLIMB-02
HER2CLIMB-02 is a global, multicenter, randomized, double-blind, placebo-controlled, Phase 3 clinical trial of tucatinib in combination with ado-trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic or unresectable breast cancer (MBC) who have had prior treatment with a taxane and trastuzumab in any setting. Trial enrollment began in 2019. The primary endpoint of the trial is PFS per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator assessment. OS, PFS by blinded independent committee review (BICR), objective response rate, duration of response, PFS and OS in patients with brain metastases at baseline, and safety and tolerability of the combination regimen are secondary objectives.
About HER2CLIMB
HER2CLIMB was a multinational randomized (2:1), double-blind, placebo-controlled, active comparator, pivotal clinical trial comparing TUKYSA in combination with trastuzumab and capecitabine compared with trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer who were previously treated with trastuzumab, pertuzumab and T-DM1. The primary endpoint of the trial was PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by blinded independent central review (BICR) in the first 480 patients enrolled in the trial. HER2CLIMB enrolled a total of 612 patients to support the analyses of key secondary endpoints, including OS, PFS per BICR in patients with brain metastases at baseline and confirmed objective response rate. Safety data were evaluated throughout the study.
About the TUKYSA Breast Cancer Development Program
About HER2-Positive Breast Cancer
An estimated 300,590 people will be diagnosed with breast cancer in
About TUKYSA (tucatinib)
TUKYSA (tucatinib) is an oral medicine that is a tyrosine kinase inhibitor of the HER2 protein. It is approved in more than 40 countries. Merck, known as MSD outside the
TUKYSA is approved in the
In combination with trastuzumab for adult patients with RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
About
Founded 25 years ago,
Forward-Looking Statements
Certain statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of TUKYSA, its safety, efficacy and therapeutic uses, the clinical development program for TUKYSA, and planned or ongoing clinical trials. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include, without limitation, the risk of delays, setbacks or failures in clinical trial and product development activities for a variety of reasons, including, without limitation, the difficulty and uncertainty of pharmaceutical product development, the possibility that clinical results may not support continued development or regulatory approvals, the risk of adverse events or safety signals, and the possibility of adverse regulatory actions. More information about the risks and uncertainties faced by
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Email: dcaouette@seagen.com
Tel: (425) 527-4160
Email: dmaffei@seagen.com
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