–Phase 2 trial showed chemotherapy-free TUKYSA combination resulted in clinically meaningful and durable tumor responses–

–Results presented in late-breaking oral session at the ESMO World Congress on Gastrointestinal Cancer–

BOTHELL, WA, USA I July 02, 2022 I Seagen Inc. (Nasdaq:SGEN) today announced full results from the pivotal phase 2 MOUNTAINEER trial, which showed TUKYSA® (tucatinib) in combination with trastuzumab was well-tolerated with durable responses in patients with previously treated HER2-positive metastatic colorectal cancer (mCRC). These late-breaking data were presented in an oral session at the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer on July 2 in Barcelona, Spain.

“Patients with chemotherapy-refractory HER2-positive metastatic colorectal cancer receive limited clinical benefit with currently available therapies,” said John H. Strickler, M.D., Associate Professor of Medicine, Duke University School of Medicine and lead trial investigator. “With sustained responses and favorable tolerability in heavily pretreated patients, tucatinib in combination with trastuzumab has the potential to be a new treatment option for previously treated HER2-positive mCRC.”

“This study has shown the benefits of dual-HER2 inhibition with tucatinib and trastuzumab in patients with HER2-positive metastatic colorectal cancer, including many whose cancer had spread to the liver or lungs before joining the trial,” said Roger Dansey, M.D., interim CEO and Chief Medical Officer, Seagen. “We believe this chemotherapy-free combination may play an important role in addressing the unmet needs of patients with this disease.”

At a median duration of follow-up of 20.7 months (interquartile range: 11.7, 39.0), results of the MOUNTAINEER trial showed a 38.1% confirmed objective response rate (cORR) (95% Confidence Interval [CI]: 27.7, 49.3) per blinded independent central review (BICR) in the HER2-positive patients who were assigned to receive tucatinib in combination with trastuzumab (n=84 with a median age of 55.0 years [range 24 to 77]). In these patients, the median duration of response (DoR) per BICR was 12.4 months (95% CI: 8.5, 20.5). Median progression-free survival per BICR was 8.2 months (95% CI: 4.2, 10.3), and median overall survival was 24.1 months (95% CI: 20.3, 36.7). At study entry, 64.3% and 70.2% of these patients had liver or lung metastases, respectively, and had received a median of 3.0 (1, 6) prior lines of systemic therapy.

In a cohort of patients who received tucatinib monotherapy (n=30), the ORR per BICR by 12 weeks was 3.3% (95% CI: 0.1, 17.2) and the disease control rate was 80.0%. Participants who did not respond to tucatinib monotherapy by 12 weeks or progressed at any time had the option to receive the combination of tucatinib and trastuzumab.

The most common (greater than or equal to 20%) treatment-emergent adverse events (AEs) in patients assigned to receive tucatinib and trastuzumab (n=86) were diarrhea (Grade 1 or 2: 60.5%, Grade 3: 3.5%), fatigue (Grade 1 or 2: 41.9%, Grade 3: 2.3%), nausea (Grade 1 or 2: 34.9%) and infusion-related reaction (Grade 1 or 2: 20.9%). The most common Grade ≥3 AE was hypertension (Grade 3: 7.0%). AEs leading to discontinuation of any treatment occurred in 5.8% of patients. No deaths due to AEs were reported. Please see Important Safety Information at the end of this press release for further safety information regarding tucatinib.

Data from this trial will form the basis of a planned supplemental New Drug Application to the U.S. Food and Drug Administration under the Accelerated Approval Program. Merck, known as MSD outside the U.S. and Canada, has exclusive rights to commercialize TUKYSA in regions outside of the U.S., Canada and Europe and plans to discuss these results with certain global health authorities.


MOUNTAINEER: Open-label, phase 2 study of tucatinib in combination with trastuzumab for HER2-positive metastatic colorectal cancer (SGNTUC-017)


LBA-2 Saturday, July 2, 2022, 12:35-12:47 CEST in Session XXII: Colorectal Cancer: Metastatic Disease J. Strickler


MOUNTAINEER is a U.S. and European multicenter, open-label, randomized phase 2 clinical trial of tucatinib in combination with trastuzumab or as a single agent that enrolled 117 patients with HER2-positive metastatic or unresectable colorectal cancer following previous standard-of-care therapies. MOUNTAINEER began as a U.S. investigator-sponsored trial and initially consisted of a single cohort (Cohort A) of patients who received tucatinib (300 mg) twice per day orally in combination with trastuzumab intravenously (8 mg/kg loading dose, then 6 mg/kg every three weeks thereafter). The trial was then expanded globally to include patients who were randomized to receive tucatinib plus trastuzumab (Cohort B) or tucatinib monotherapy (Cohort C).

The primary endpoint of the trial is confirmed objective response rate by RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1 criteria per blinded independent central review in patients receiving the combination of tucatinib and trastuzumab (Cohorts A and B). Duration of response, progression-free survival, overall survival and safety and tolerability of the combination regimen are secondary objectives.

About Colorectal Cancer

Globally, more than 1.9 million new colorectal cancer cases and 935,000 deaths were estimated to occur in 2020, representing about one in 10 cancer cases and deaths.1 Colorectal cancer is the third leading cause of cancer-related deaths in the U.S. and is anticipated to lead to about 52,580 deaths in 2022.2 Approximately 22% of U.S. patients with colorectal cancer are diagnosed at the advanced stage.3 Human epidermal growth factor receptor 2 (HER2) is overexpressed in 3-5% of patients with metastatic colorectal cancer.4,5 There are currently no FDA-approved therapies that specifically target HER2 in colorectal cancer.


TUKYSA is an oral medicine that is a tyrosine kinase inhibitor of the HER2 protein. In vitro (in lab studies), TUKYSA inhibited phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell growth (proliferation), and showed anti-tumor activity in HER2-expressing tumor cells. In vivo (in living organisms), TUKYSA inhibited the growth of HER2-expressing tumors. The combination of TUKYSA and the anti-HER2 antibody trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either medicine alone.

TUKYSA is approved in 36 countries. It was approved by the U.S. FDA in April 2020 and by the European Medicines Agency and the UK Medicines and Healthcare Products Regulatory Agency in February 2021. Merck, known as MSD outside the U.S. and Canada, has exclusive rights to commercialize TUKYSA in Asia, the Middle East and Latin America and other regions outside of the U.S., Canada and Europe.

U.S. Indication and Important Safety Information

TUKYSA is indicated in combination with trastuzumab and capecitabine for treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.

For more information, please see the full Prescribing Information for TUKYSA here.

About Seagen

Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people’s lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company’s marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

1 American Cancer Society Journal: Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21660. Accessed June 2022.

2 American Cancer Society: Key Statistics for Colorectal Cancer-2022. https://www.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html. Accessed March 2022.

3 Wang J., et al. Metastatic patterns and survival outcomes in patients with stage IV colon cancer: A population-based analysis. Cancer Med. 2020 Jan; 9(1): 361–373.

4 Takegawa N and Yonesaka K (2017). HER2 as an emerging oncotarget for colorectal cancer treatment after failure of anti-epidermal growth factor receptor therapy. Clin Colorectal Cancer 16: 247-51.

5 Valtorta E., et al. Assessment of a HER2 scoring system for colorectal cancer: results from a validation study. Mod Pathol 28: 1481-91 2015.