Tucatinib monotherapy and tucatinib plus trastuzumab for HER2-positive (HER2+) were well-tolerated in the crossover population of the MOUNTAINEER trial. Further analyses also showed disease stabilization in most patients on tucatinib monotherapy and increased radiographic responses after the addition of trastuzumab. Additionally, the data show that concurrent initiation of dual HER2 blockade with tucatinib and trastuzumab achieves optimal clinical benefit.

Data from these additional analyses were presented on Monday, September 12, 2022, at the European Society for Medical Oncology Congress in Paris, France, by first author, John Strickler, MD, Duke Cancer Center, Durham, United States.

In the open-label, phase 2 MOUNTAINEER, patients with HER2+ metastatic colorectal cancer were initially enrolled into Cohort A and received treatment with tucatinib orally twice daily on Days 1 through 22 and trastuzumab intravenously on Day 1. Following that stage, patients were randomized to receive either the same treatment regimen as Cohort A (Cohort B) or tucatinib twice per day orally with the option to crossover to the tucatinib plus trastuzumab regimen if they do not respond (Cohort C). Results of the primary analysis in cohorts A and B were previously reported and showed that tolerability and a confirmed objective response rate (ORR) of 38.1%. The current data reflects additional results from Cohort C.

As of the data cutoff date of March 28, 2022, 86 patients in Cohorts A+B and 30 patients in Cohort C received at least 1 dose of study treatment. At week 12, the ORR of Cohort C was 3.3% (95% confidence interval [CI], 0.1 to 17.2) and the disease control rate (DCR) was 80%. Of those 30 patients in cohort C, 93% crossed over to the combination therapy, with a confirmed ORR of 17.9% (95% CI, 6.1 to 36.9).

The most common adverse events in Cohort C were diarrhea, abdominal pain, and faigue which were all grade 1/2. The most common grade ≥3 events were ALT-ASP increase. After crossover, the most common adverse event was grade 1/2 diarrhea while the most common grade ≥3 adverse events were ALT/AST increase. There were no fatal adverse events on either regimen

Source:

Strickler J, Cercek A, Siena S, et al. “Additional analyses of MOUNTAINEER: A phase II study of tucatinib and trastuzumab for HER2-positive mCRC.” Presented at European Society for Medical Oncology Congress; September 9-13, 2022. Paris, France.