The US Food and Drug Administration (FDA) has accepted for priority review the supplemental new drug application (sNDA) for tucatinib in combination with trastuzumab for adults with HER2-positive colorectal cancer who have received at least 1 prior treatment regimen for unresectable or metastatic disease.
The sNDA is based on data from the multicenter, open-label phase 2 MOUNTAINEER trial (ClinialTrials.gov Identifier: NCT03043313), which evaluated tucatinib alone or in combination with trastuzumab in 117 patients with HER2-positive unresectable or metastatic colorectal cancer following previous standard of care therapies. Patients received tucatinib at 300 mg orally twice daily in combination with trastuzumab intravenously (8 mg/kg loading dose, then 6 mg/kg every 3 weeks thereafter).
The primary endpoint was confirmed objective response rate (ORR). Key secondary endpoints included duration of response (DoR), progression-free survival (PFS), and overall survival (OS).
At a median follow-up of 20.7 months, the ORR was 38.1% (95% CI, 27.7-49.3) among the 84 patients who received tucatinib plus trastuzumab. The median DoR was 12.4 months (95% CI, 8.5-20.5), the median PFS was 8.2 months (95% CI, 4.2-10.3), and the median OS was 24.1 months (95% CI, 20.3-36.7).
The most common treatment-emergent adverse events were diarrhea, fatigue, nausea, and infusion-related reactions. The most common grade 3 or higher adverse event was hypertension.
“There are currently no FDA-approved therapies for metastatic colorectal cancer that specifically target HER2,” said Marjorie Green, MD, senior vice president and head of late-stage development at Seagen. “The FDA’s prioritization of our application for tucatinib in combination with trastuzumab supports our belief in its significant potential to benefit people with previously treated HER2-positive metastatic colorectal cancer.”
A Prescription Drug User Fee Act target action date of January 19, 2023 has been set for the application.
Tucatinib, a tyrosine kinase inhibitor of the HER2 protein, is currently marketed under the brand name Tukysa®, for use in combination with trastuzumab and capecitabine, for the treatment of patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received 1 or more prior anti-HER2-based regimens in the metastatic setting.
- Seagen announces Tukysa® (tucatinib) in combination with trastuzumab granted Priority Review by FDA for previously treated HER2-positive metastatic colorectal cancer. News release. Seagen. Accessed September 19, 2022. https://www.businesswire.com/news/home/20220919005223/en/Seagen-Announces-TUKYSA%C2%AE-tucatinib-in-Combination-with-Trastuzumab-Granted-Priority-Review-by-FDA-for-Previously-Treated-HER2-Positive-Metastatic-Colorectal-Cancer
- 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 September 19, 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
This article originally appeared on MPR