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A phase II, open label study of tucatinib (ONT-380) combined with trastuzumab in patients with HER2+ metastatic colorectal cancer (mCRC)(MOUNTAINEER).

Publication ,  Conference
Strickler, JH; Niedzwiecki, D; Zemla, T; Cercek, A; Fakih, M; Ng, K; Sanchez, FA; Wu, CS-Y; Peterson, S; Bandel, L; Grothey, A; Bekaii-Saab, TS
Published in: Journal of Clinical Oncology
May 20, 2017

TPS3624 Background: To improve survival for patients with mCRC, efforts are needed to identify and treat actionable genomic alterations. HER2 is amplified in approximately 5-8% of patients with KRAS and NRAS (RAS) wild-type mCRC. HER2 functions as an oncogenic driver and a mediator of EGFR antibody (Ab) resistance. Although prior studies have shown that anti-HER2 therapies are active in patients with HER2+ (HER2 IHC 3+ or HER2 amplified) mCRC, there are no HER2-directed therapies approved for these patients. Tucatinib is a potent and highly selective oral small molecule tyrosine kinase inhibitor of HER2, currently being developed to treat metastatic breast cancer. In HER2+ CRC patient derived xenograft models, tucatinib has substantial anti-tumor activity. The addition of the anti-HER2 monoclonal Ab trastuzumab augments tumor growth inhibition. Methods: This single-arm phase II study will test the combination of tucatinib and trastuzumab in patients with HER2+ mCRC. Eligible patients include those with RAS wild-type mCRC who have been previously treated with 5-FU, oxaliplatin, irinotecan, and an anti-VEGF monoclonal Ab. Patients must have HER2+ disease by IHC, FISH, or NGS. Prior treatment with anti-HER2 targeting therapy is excluded. The primary objective is to assess the objective response rate for the combination. Secondary objectives are to evaluate the efficacy (PFS, OS, clinical benefit rate), safety, and tolerability of the combination. Correlation between tissue and blood-based biomarkers and clinical outcomes will be explored. Blood will be collected at baseline and each restaging to determine if the combination eliminates HER2 amplified circulating tumor DNA. Subjects will receive tucatinib at a dose of 300mg by mouth daily, and trastuzumab will be administered every 3 weeks (8 mg/kg IV day 1 of cycle 1, then 6 mg/kg IV Q3 weeks). Response will be assessed every 3 cycles (9 weeks) per RECIST version 1.1. Both agents will be provided by the study. This study was initiated in February 2017. Recruitment is ongoing at 8 sites in the Academic and Community Cancer Research United (ACCRU) network. Clinical trial information: NCT03043313.

Duke Scholars

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

May 20, 2017

Volume

35

Issue

15_suppl

Start / End Page

TPS3624 / TPS3624

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Strickler, J. H., Niedzwiecki, D., Zemla, T., Cercek, A., Fakih, M., Ng, K., … Bekaii-Saab, T. S. (2017). A phase II, open label study of tucatinib (ONT-380) combined with trastuzumab in patients with HER2+ metastatic colorectal cancer (mCRC)(MOUNTAINEER). In Journal of Clinical Oncology (Vol. 35, pp. TPS3624–TPS3624). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2017.35.15_suppl.tps3624
Strickler, John H., Donna Niedzwiecki, Tyler Zemla, Andrea Cercek, Marwan Fakih, Kimmie Ng, Federico Augusto Sanchez, et al. “A phase II, open label study of tucatinib (ONT-380) combined with trastuzumab in patients with HER2+ metastatic colorectal cancer (mCRC)(MOUNTAINEER).” In Journal of Clinical Oncology, 35:TPS3624–TPS3624. American Society of Clinical Oncology (ASCO), 2017. https://doi.org/10.1200/jco.2017.35.15_suppl.tps3624.
Strickler JH, Niedzwiecki D, Zemla T, Cercek A, Fakih M, Ng K, et al. A phase II, open label study of tucatinib (ONT-380) combined with trastuzumab in patients with HER2+ metastatic colorectal cancer (mCRC)(MOUNTAINEER). In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2017. p. TPS3624–TPS3624.
Strickler, John H., et al. “A phase II, open label study of tucatinib (ONT-380) combined with trastuzumab in patients with HER2+ metastatic colorectal cancer (mCRC)(MOUNTAINEER).Journal of Clinical Oncology, vol. 35, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2017, pp. TPS3624–TPS3624. Crossref, doi:10.1200/jco.2017.35.15_suppl.tps3624.
Strickler JH, Niedzwiecki D, Zemla T, Cercek A, Fakih M, Ng K, Sanchez FA, Wu CS-Y, Peterson S, Bandel L, Grothey A, Bekaii-Saab TS. A phase II, open label study of tucatinib (ONT-380) combined with trastuzumab in patients with HER2+ metastatic colorectal cancer (mCRC)(MOUNTAINEER). Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2017. p. TPS3624–TPS3624.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

May 20, 2017

Volume

35

Issue

15_suppl

Start / End Page

TPS3624 / TPS3624

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences