On July 2, 2022, Seagen announced the full results of the pivotal Phase 2 MOUNTAINEER trial, demonstrating that tucatinib (trademark: TUKYSA) in combination with trastuzumab was well-tolerated and showed durable responses in patients with previously treated HER2-positive metastatic colorectal cancer (mCRC). These latest data were presented orally at the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer in Barcelona, Spain on July 2.
Tucatinib (Tukysa) is an oral TKI for the HER2 protein. In vitro, this drug has been shown to inhibit the phosphorylation of HER2 and HER3, thereby inhibiting downstream MAPK and AKT signaling and cell growth. The drug has also shown antitumor activity in tumor cells expressing HER2.
“This study demonstrates the benefit of dual inhibition of HER2 by tucatinib and trastuzumab in patients with HER2-positive metastatic colorectal cancer, including many who had cancer that had spread to the liver or lungs before enrolling in the trial,” said Roger Dansey, CEO and Chief Medical Officer of Seagen. “We believe this chemotherapy-free combination may play a significant role in addressing an unmet need in patients with this disease.”
At a median follow-up duration of 20.7 months (interquartile range: 11.7, 39.0), results from the MOUNTAINEER trial showed a confirmed objective response rate (cORR) of 38.1% per blinded independent central review (BICR) in HER2-positive patients (n=84, median age 55.0 years [range: 24–77]) (95% confidence interval [CI]: 27.7, 49.3).
In these patients, the median duration of response (DoR) per BICR was 12.4 months (95% CI: 8.5, 20.5). The median progression-free survival (PFS) for each BICR was 8.2 months (95% CI: 4.2, 10.3), and the median overall survival (OS) was 24.1 months (95% CI: 20.3, 36.7).
At the start of the study, 64.3% and 70.2% of these patients, respectively, had liver or lung metastases and had received a median of 3.0 (1, 6) prior systemic therapy.
In the group receiving tucardinib monotherapy (n=30), the objective response rate (ORR) at 12 weeks per BICR was 3.3% (95% CI: 0.1, 17.2), and the disease control rate was 80.0%. Participants who did not respond to tucardinib monotherapy within 12 weeks or who progressed at any time could choose to receive combination therapy with tucardinib and trastuzumab.
The most common adverse events (AEs) occurring in patients assigned to receive tucatinib and trastuzumab (n=86) were in ≥20% of cases: 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 reactions (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.
Data from this trial will form the basis for a planned supplemental New Drug Application (PDA) to be submitted to the FDA under the Accelerated Approval Program.
