|Seattle Genetics Announces Publication of Results from Two Tucatinib Phase 1b Clinical Trials in HER2-Positive Metastatic Breast Cancer|
Results of Combination “Triplet” of Tucatinib with Trastuzumab and Capecitabine Published in The Lancet Oncology
Results of Tucatinib in Combination with Ado-trastuzumab Emtansine Published in JAMA Oncology
“There remains a need for a well-tolerated, oral targeted therapy to
treat patients with HER2+ metastatic breast cancer whose disease
progresses on conventional anti-HER2 treatments, particularly for those
whose cancer has metastasized to the brain, which occurs in up to 50
percent of these patients,” said
“The results of the combination tucatinib with trastuzumab and
capecitabine triplet study support the development of this regimen in
the ongoing pivotal HER2CLIMB trial to provide a meaningful advancement
in the use of targeted therapies to treat this disease,” said
The manuscript entitled “Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomized, open-label, phase 1b study” was published in the July print edition of The Lancet Oncology.
The phase 1b triplet study was an open-label dose-escalation and expansion cohort study of tucatinib in combination with capecitabine and/or trastuzumab in patients with HER2+ metastatic breast cancer, including those with or without brain metastases. The objective of the study was to assess the safety, tolerability, pharmacokinetics and antitumor activity, and to determine the recommended phase 2 dose of tucatinib in combination with these agents. Once a recommended phase 2 dose of 300 mg BID was established in the triplet combination, an expansion cohort using that regimen was opened. The trial enrolled 60 patients with HER2+ metastatic breast cancer who had previously received a median of three HER2-targeted agents, such as trastuzumab, pertuzumab (Perjeta®), lapatinib (Tykerb®) or T-DM1.
Data from patients treated with the triplet combination at 300 mg BID (n=27) included:
An ongoing randomized, double-blind, placebo-controlled pivotal trial called HER2CLIMB is comparing tucatinib vs. placebo, each in combination with capecitabine and trastuzumab in patients with pretreated, unresectable, locally advanced or metastatic HER2+ breast cancer, including patients with or without brain metastases.
“The combination of tucatinib and T-DM1 in the phase 1b clinical
trial was tolerable and appeared to show antitumor activity among
heavily pretreated patients with HER2+ metastatic breast cancer with and
without brain metastases,” said
The manuscript entitled “Tucatinib combined with ado-trastuzumab emtansine in advanced HER2-positive metastatic breast cancer: A phase 1b open-label clinical trial” was published in the July print edition of JAMA Oncology.
This phase 1b, open-label dose escalation and expansion cohort study of tucatinib in combination with T-DM1 enrolled 57 patients with HER2+ breast cancer. The objective of the study was to assess the safety, tolerability, pharmacokinetics and antitumor activity, and to determine the recommended phase 2 dose of tucatinib in combination with T-DM1. Participants in the study previously received a median of two prior HER2-directed therapies.
Data from the phase 1b study of tucatinib and T-DM1 (n=57) included:
Tucatinib is an investigational, orally bioavailable, potent tyrosine
kinase inhibitor that is highly selective for HER2 without significant
inhibition of EGFR. Inhibition of EGFR has been associated with
significant toxicities, including skin rash and diarrhea. Tucatinib has
shown activity as a single agent and in combination with both
chemotherapy and other HER2 directed agents such as trastuzumab.1,2
Studies of tucatinib in these combinations have shown activity both
systemically and in brain metastases. HER2 is a growth factor receptor
that is overexpressed in multiple cancers, including breast, ovarian and
gastric cancers. HER2 mediates cell growth, differentiation and
survival. Tumors that overexpress HER2 are more aggressive and
historically have been associated with poor overall survival, compared
with HER2-negative cancers. Tucatinib has been granted orphan drug
designation by the
About HER2-Positive Metastatic Breast Cancer
Patients with HER2-positive breast cancer have tumors with high levels
of a protein called human epidermal growth factor receptor 2 (HER2),
which promotes the aggressive spread of cancer cells.
Certain of the statements made in this press release are forward
looking, such as those, among others, relating to therapeutic potential
of tucatinib, its possible safety, efficacy, and therapeutic uses and
anticipated development activities including the continued enrollment of
patients in HER2CLIMB, development of tucatinib for breast and other
cancers, future clinical trials and intended regulatory actions. 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 the difficulty and uncertainty of pharmaceutical
product development, including the inability to show sufficient activity
in the clinical trials, the risk of adverse events or safety signals,
and the possibility of adverse regulatory actions as tucatinib advances
in clinical trials even after promising results in earlier clinical
trials. More information about the risks and uncertainties faced by
1. Moulder, S. et al., Phase 1 Trial of ONT-380, a HER2 Inhibitor, in
Patients with HER2+ Advanced Solid Tumors, with an Expansion Cohort in
HER2+ Metastatic Breast Cancer.
3. ASCO Cancer.Net, Treatment of Metastatic HER2-Positive Breast Cancer.
4. Metro, et al., Clinical outcome of patients with brain metastases from HER2-positive breast cancer treated with lapatinib and capecitabine. Annals of Oncology, vol. 212, no. 3, pp. 625-630, 2011.
5. Ramakrishna N., et al.,