There are currently no FDA-approved targeted therapies for HER2-positive colorectal cancer, and the available treatments for chemotherapy-resistant HER2-positive metastatic colorectal cancer patients offer limited clinical benefit.
At the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer, Seagen presented oral results from the MOUNTAINEER trial (LBA-2) of tucatinib in combination with trastuzumab for the treatment of previously treated HER2-positive metastatic colorectal cancer. Data showed that the chemotherapy-free tucatinib combination produced a clinically meaningful and durable tumor response. The median follow-up was 20.7 months, and the objective response rate (cORR) was 38.1%.
On September 19th, Seagen The company announces FDA I have received second-line treatment with the combination of tocatinib and trastuzumab HER2 Priority review application for accelerated approval of supplementary new drug application (sNDA) for adult patients with positive colorectal cancer (mCRC). According to the Prescription Drug User Fee Act (PDUFA), an approval decision is expected to be made on January 19, 2023.
In 2022, approximately 151,000 people in the United States were diagnosed with colorectal cancer, with about 22% diagnosed at an advanced stage, and the disease is increasingly affecting younger people. Colorectal cancer is projected to cause approximately 52,500 deaths in the United States in 2022, ranking third among cancer-related deaths. HER2 is overexpressed in 3% to 5% of patients with metastatic colorectal cancer.
Tacotinib is an oral small-molecule HER2 kinase inhibitor that inhibits HER2 and HER3 phosphorylation, thereby suppressing downstream MAPK and AkT signaling pathways and cell growth (proliferation), and exhibits antitumor activity in HER2-expressing tumor cells. In vivo (in living organisms), tacotinib inhibits the growth of tumors that overexpress HER2. The combination of tacotinib and trastuzumab shows superior antitumor activity both in vitro and in vivo compared to either drug alone.
Tacitinib was first approved by the FDA in 2020 and has since been approved in 38 countries. It is used in combination with trastuzumab and capecitabine for unresectable locally advanced or metastatic HER2-positive breast cancer that has failed prior anti-HER2 therapy. Global sales reached $334 million in 2021. This sNDA for adult patients with HER2-positive colorectal cancer is based on the results of the pivotal Phase II MOUNTAINEER trial, with specific data presented at the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer in July 2022.
MOUNTAINEER is an open-label, multicenter phase II clinical trial in the United States and Europe that enrolled 117 patients with HER2-positive unresectable or metastatic colorectal cancer who had previously received standard treatment, using tucatinib in combination with trastuzumab or as monotherapy.
Patients evaluated in the MOUNTAINEER trial had not previously received anti-HER2 therapy. Patients received oral tacotinib (300 mg) twice daily followed by intravenous trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks). The primary endpoint of this trial was objective response rate confirmed by blinded independent central review according to RECIST (Responsive Criteria for Solid Tumor Response) version 1.1 criteria; secondary endpoints included duration of response, progression-free survival, overall survival, safety, and tolerability.
“The FDA has not yet approved a therapy for HER2-positive metastatic colorectal cancer,” said Dr. Marjorie Green, Senior Vice President and Head of Late-Stage Development at Seagen. “The FDA's priority review of tucatinib in combination with trastuzumab indicates its significant potential to benefit patients with previously treated HER2-positive metastatic colorectal cancer.”
