Seattle Genetics Announces Initial Results from MOUNTAINEER Trial Showing Antitumor Activity of Tucatinib Combination in HER2-Positive Metastatic Colorectal Cancer

Seattle Genetics announced initial data from the phase 2 MOUNTAINEER trial, evaluating tucatinib in combination with trastuzumab (Herceptin) in patients with HER2-positive (HER2+), RAS wild-type metastatic colorectal cancer (mCRC) after treatment with first- and second-line standard-of-care therapies. The regimen demonstrated encouraging antitumor activity and was well tolerated. The results were presented during a poster discussion session at the European Society for Medical Oncology (ESMO) 2019 Congress in Barcelona, Spain.

MOUNTAINEER is a multi-center, open-label, single-arm phase 2 clinical trial of tucatinib in combination with trastuzumab in patients with HER2-positive, RAS wild-type metastatic or unresectable colorectal cancer. The primary endpoint of the trial is the objective response rate by RECIST (Response Evaluation Criteria in Solid Tumors) v1.1 criteria. Progression-free survival, duration of response, overall survival and safety and tolerability of the combination regimen are secondary objectives. 

Initial results from 23 patients evaluable for clinical/radiographic response are as follows: 

  • Objective response rate (ORR) was 52.2% with a median duration of response of 10.4 months 
  • Median progression-free survival (PFS) was 8.1 months 
  • Median overall survival (OS) was 18.7 months 
  • The combination of tucatinib and trastuzumab was well tolerated. The most common treatment-related adverse events were Grade 1 in severity and included increased aspartate aminotransferase, increased alanine aminotransferase, and diarrhea. There were no Grade 4 or 5 treatment-related adverse events. 

About Colorectal Cancer

Colorectal cancer is the second leading cause of cancer death in the United States (U.S.). In 2019, it is estimated there will be 145,600 new cases and 51,020 deaths in the U.S.5 Approximately 21 percent of U.S. patients with colorectal cancer are diagnosed at the advanced stage.  According to the U.S. Centers for Disease Control and Prevention, the most effective way to reduce the risk of colorectal cancer is routine screening beginning at age 50. In colorectal cancer, human epidermal growth factor receptor 2 (HER2) is overexpressed in three-to-five percent of patients. There are currently no therapies approved that specifically target HER2 in colorectal cancer.

About Tucatinib

Tucatinib is an 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. 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, colorectal 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 FDA for the treatment of HER2-positive metastatic colorectal cancer and breast cancer patients with brain metastases.