Strickler John H, Bekaii-Saab Tanios, Cercek Andrea, Heinemann Volker, Nakamura Yoshiaki, Raghav Kanwal, Siena Salvatore, Tabernero Josep, Van Cutsem Eric, Yoshino Takayuki, Ramos Jorge, Guan Xuesong, Andre Thierry
Division of Medical Oncology, Duke University Medical Center, Durham, NC, USA.
Division of Hematology and Medical Oncology, Mayo Clinic, Phoenix, AZ, USA.
Future Oncol. 2025 Feb;21(3):303-311. doi: 10.1080/14796694.2024.2441101. Epub 2024 Dec 26.
Patients diagnosed with metastatic colorectal cancer (mCRC) have a poor prognosis with survival ranging 2-3 years. The prevalence of human epidermal growth factor receptor 2 (HER2) amplification is approximately 3-4% in mCRC and increases up to 8% in patients with // wild-type (WT) CRC tumors. Tucatinib is a highly selective HER2-directed tyrosine kinase inhibitor that, in combination with trastuzumab, has demonstrated clinically meaningful activity in patients with chemotherapy-refractory, HER2-positive (HER2+), WT mCRC in the MOUNTAINEER trial. The MOUNTAINEER-03 phase III trial is designed to investigate the efficacy and safety of first-line tucatinib in combination with trastuzumab and modified FOLFOX6 (mFOLFOX6) versus standard of care (mFOLFOX6 plus bevacizumab or cetuximab) in patients with untreated HER2+, WT locally advanced unresectable or mCRC. MOUNTAINEER-03 will include two arms of approximately 400 patients randomized 1:1 to either treatment arm. The primary endpoint is progression-free survival per RECIST v1.1 by blinded independent central review (BICR). Key secondary endpoints are overall survival and confirmed objective response rate (according to RECIST v1.1 per BICR). Safety assessments will include surveillance and recording of adverse events, physical examination findings, vital signs, cardiac assessments, Eastern Cooperative Oncology Group performance status, concomitant medications, and laboratory tests. NCT05253651 (ClinicalTrials.gov).
被诊断为转移性结直肠癌（mCRC）的患者预后较差，生存期为2至3年。在mCRC中，人表皮生长因子受体2（HER2）扩增的发生率约为3%-4%，在野生型（WT）结直肠癌肿瘤患者中这一比例增至8%。图卡替尼是一种高度选择性的HER2靶向酪氨酸激酶抑制剂，在MOUNTAINEER试验中，它与曲妥珠单抗联合使用，已在化疗难治性、HER2阳性（HER2+）、WT mCRC患者中显示出具有临床意义的活性。MOUNTAINEER-03 III期试验旨在研究一线图卡替尼联合曲妥珠单抗和改良FOLFOX6（mFOLFOX6）与标准治疗（mFOLFOX6加贝伐单抗或西妥昔单抗）相比，在未经治疗的HER2+、WT局部晚期不可切除或mCRC患者中的疗效和安全性。MOUNTAINEER-03将包括两个治疗组，每组约400名患者，按1:1随机分配至任一治疗组。主要终点是由盲态独立中央审查（BICR）根据RECIST v1.1标准评估的无进展生存期。关键次要终点是总生存期和确认的客观缓解率（根据BICR的RECIST v1.1标准）。安全性评估将包括不良事件的监测和记录、体格检查结果、生命体征、心脏评估、东部肿瘤协作组体能状态、伴随用药以及实验室检查。NCT05253651（ClinicalTrials.gov）
