Background of the MOUNTAINEER-03 Study in HER2+ Metastatic Colorectal Cancer

Tanios Bekaii-Saab, MD, FACP, discusses background that led to the start of the MOUNTAINEER-03 trial.

Tanios Bekaii-Saab, MD, FACP, medical oncologist, medical director, Cancer Clinical Research Office, vice chair and section chief, medical oncology, Department of Internal Medicine, Mayo Clinic, Phoenix, Arizona, discusses background that led to the start of the MOUNTAINEER-03 trial (NCT05253651).

The phase 3 MOUNTAINEER-03 study is ongoing and evaluating the combination of tucatinib (Tukysa), trastuzumab (Herceptin), and 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) in the first-line setting for patients with HER2-positive metastatic colorectal cancer (mCRC).

However, this study is a follow-up from the positive phase 2 MOUNTAINEER trial (NCT03043313). In this study, investigators assessed the combination of tucatinib and trastuzumab in this patient population.


0:08 | The data that led to the MOUNTAINEER-03 trial were from a study called MOUNTAINEER, led by John Strickler, MD and myself, which looked at the role of tucatinib added to trastuzumab in patients with HER2-amplified metastatic colorectal cancer. To go through the background, HER2 is present and amplified in about 3%-4% of all [patients] with metastatic colorectal cancer.

1:00 | HER2 seems to be 1 of the major drivers of carcinogenesis in colorectal cancer. Of interest to us are mostly those RAS wild-type HER2-amplified tumors, which represent about 70% of all the HER2-amplified tumors. There was some early clinical data suggesting that the dual targeting of HER2-targeting agents have yielded responses in the 30% or so range.

1:57 | Essentially, that led to the development of the idea of taking tucatinib, which is a highly potent oral agent for HER2 and does not have some of the [negative] aspects of lapatinib [Tykerb], and it is more specific. You would imagine less off-target toxicities, which was of interest to us. Then combining that with trastuzumab. There was some preclinical data suggesting that you would see nice trends with the combination of the tucatinib and trastuzumab in HER2-positive preclinical models. That led to MOUNTAINEER essentially.

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