In the phase 2 MOUNTAINEER study, the investigational combination of tucatinib and trastuzumab achieved durable response in patients with metastatic colorectal cancer.
Breaking data, presented at the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer, revealed durable responses in patients diagnosed with HER2-positive metastatic colorectal cancer (mCRC) treated with tucatinib (Tukysa) in combination with trastuzumab (Herceptin). These full results from the phase 2 MOUNTAINEER study (NCT03043313) were announced by Seagen Inc., in a press release.1
With a median duration of follow-up of 20.7 months (interquartile range, 11.7-39.0), patients with HER2-positive mCRC receiving tucatinib and trastuzumab (n = 84) had a confirmed objective response rate (cORR) of 38.1% (95% CI, 27.7%-49.3%) per blinded independent central review (BICR). The median duration of response (DOR) in these patients per BICR was 12.4 months (95% CI, 8.5-20.5).
“Patients with chemotherapy-refractory HER2-positive metastatic colorectal cancer receive limited clinical benefit with currently available therapies,” John H. Strickler, MD, associate professor of medicine, Duke University School of Medicine and lead trial investigator said, in the 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.”
“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, MD, interim chief executive officer and chief medical officer at Seagen Inc. “We believe this chemotherapy-free combination may play an important role in addressing the unmet needs of patients with this disease.”
The US and European multicenter, open-label, randomized MOUNTAINEER trial compared tucatinib in combination with trastuzumab or as a single agent in 117 patients with HER2-positive mCRC or unresectable colorectal cancer following previous standard-of-care therapies. This trial initially studied a one cohort (Cohort A) of patients who received tucatinib at 300 mg doses twice per day in combination with intravenous trastuzumab at an 8 mg/kg loading dose followed by 6 mg/kg doses every 3 weeks after. The trial expanded globally and included Cohort B, where patients received tucatinib plus trastuzumab, and Cohort C, where patients received tucatinib monotherapy.
The primary end point of the study is cORR by RECIST version 1.1 criteria per BICR in cohorts A and B. Secondary end points included DOR progression-free survival (PFS), overall survival (OS), and safety and tolerability of the treatment combination.
Patients receiving combination therapy had a PFS per BICR of 8.2 months (95% CI, 4.2-10.3), and median OS was 24.1 months (95% CI, 20.3-36.7).
The median age of patients receiving combination therapy was 55.0 years (range, 24-77). At baseline, 64.3% of these patients had liver metastases and 70.2% had lung metastases. Median prior lines of systemic therapy received by these patients was 3.0 (range, 1-6).
Patients who received tucatinib monotherapy (n = 30) had an ORR per BICR of 3.3% (5% CI, 0.1%-17.2%) by 12 weeks. The disease control rate was 80.0%. Patients had the option to receive combination therapy if they did not respond to tucatinib monotherapy by 12 weeks or progressed at any time.
Patients who were assigned to receive tucatinib and trastuzumab therapy mostly reported grades 1 or 2 diarrhea (60.5%), grades 1 or 2 fatigue (41.9%) and grades or 2 nausea (34.9%), and grades 1 or 2 infusion-related reaction (20.9%) as treatment-emergent adverse events (TRAEs). Grade 3 TRAEs in this group included diarrhea (3.5%) and fatigue (2.3%). The most common grade 3 AE was hypertension (7.0%). AEs led to treatment discontinuation in 5.8% of all patients across all treatments. No deaths were due to AEs.
This trial’s data will form the basis for a supplemental new drug application that will be submitted to the FDA under an accelerated approval program.
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. Press release. Seagen; July 2, 2022. Accessed July 7, 2022. https://bit.ly/3nMuXcs