Results from pivotal MOUNTAINEER trial demonstrating clinically meaningful antitumor activity of Tukysa + Trastuzumab in previously treated HER2-positive metastatic colorectal cancer.-Seagen Inc. + Merck Inc.

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.”

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 greater than 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.

Data from this trial will form the basis of a planned supplemental New Drug Application to the FDA under the Accelerated Approval Program. Merck Inc., 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.