Pivotal Trial Demonstrates Antitumor Activity With Tucatinib, Trastuzumab in Previously Treated HER2-Positive Metastatic Colorectal Cancer

Data from the pivotal phase 2 MOUNTAINEER trial has found that tucatinib (Tukysa, Seagen) in combination with trastuzumab resulted in clinically meaningful and durable tumor responses among patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive metastatic colorectal cancer (mCRC).

MOUNTAINEER is a multicenter, open-label, randomized phase 2 clinical trial investigating tucatinib as a single agent or in combination with trastuzumab. The trial enrolled 117 patients with HER2-positive metastatic or unresectable colorectal cancer following previous standard-of-care therapies.

The trial originally consisted of a single cohort of patients who received tucatinib (300 mg) twice per day orally in combination with trastuzumab intravenously (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks). The trial was then expanded globally to include patients who were randomized to receive tucatinib plus trastuzumab or tucatinib monotherapy.

The late-breaking data were presented in an oral session at the European Society for Medical Oncology World Congress. At a median duration of follow-up of 20.7 months, the results showed a 38.1% confirmed objective response rate (ORR) among the HER2-positive patients who received tucatinib in combination with trastuzumab.

“Patients with chemotherapy-refractory HER2-positive metastatic colorectal cancer receive limited clinical benefit with currently available therapies,” lead trial investigator John H. Strickler, MD, said in a press release. “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.”

Among the HER2-positive patients who received the combination treatment, the median duration of response per blinded independent central review was 12.4 months. Furthermore, median progression-free survival (PFS) was 8.2 months, and median overall survival (OS) was 24.1 months. At study entry, 64.3% and 70.2% of these patients had liver or lung metastases, respectively, and had received a median of 3 prior lines of systemic therapy.

In the cohort of patients who received tucatinib monotherapy, the ORR by 12 weeks was 3.3% and the disease control rate was 80%. Participants who did not respond to monotherapy by 12 weeks or who progressed at any time had the option to receive the combination of tucatinib and trastuzumab, according to the study.

The most common treatment-emergent adverse events (AEs) in patients assigned to the combination therapy were diarrhea, fatigue, nausea, and infusion-related reaction. The most common grade 3 or higher AE was hypertension (7% grade 3), and AEs leading to discontinuation of any treatment occurred in 5.8% of patients. No deaths due to AEs were reported.

Globally, more than 1.9 new colorectal cancer cases and 935,000 deaths were estimated to occur in 2020, representing approximately 1 in 10 cancer cases and deaths. Colorectal cancer is the third leading cause of cancer-related deaths in the United States and is anticipated to result in about 52,580 deaths in 2022.

“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,” Roger Dansey, MD, interim CEO and chief medical officer at Seagen, said in the press release. “We believe this chemotherapy-free combination may play an important role in addressing the unmet needs of patients with this disease.”

REFERENCE

Seagen Announces Results from Pivotal MOUNTAINEER Trial Demonstrating Clinically Meaningful Antitumor Activity of TUKYSA (tucatinib) in Combination with Trastuzumab in Previously Treated HER2-Positive Metastatic Colorectal Cancer. News release. Seagen; July 2, 2022. Accessed July 11, 2022. https://investor.seagen.com/press-releases/news-details/2022/Seagen-Announces-Results-from-Pivotal-MOUNTAINEER-Trial-Demonstrating-Clinically-Meaningful-Antitumor-Activity-of-TUKYSA-tucatinib-in-Combination-with-Trastuzumab-in-Previously-Treated-HER2-Positive-Metastatic-Colorectal-Cancer/default.aspx