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MOUNTAINEER-02: Phase II/III study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2+ gastric or gastroesophageal junction adenocarcinoma—Trial in Progress.

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Strickler, JH; Nakamura, Y; Yoshino, T; Catenacci, DVT; Janjigian, YY; Barzi, A; Bekaii-Saab, TS; Lenz, H-J; Lee, J; Van Cutsem, E; Chung, HC ...
Published in: Journal of Clinical Oncology
January 20, 2021

TPS252 Background: Tucatinib (TUC), a highly selective HER2-directed TKI recently approved for HER2+ metastatic breast cancer (MBC), is being developed as a novel therapy for patients (pts) with metastatic colorectal cancer (mCRC) and other GI tumors. While trastuzumab (Tras) with chemotherapy is standard in the 1st-line setting for metastatic HER2+ gastric or gastroesophageal junction adenocarcinoma (GEC), no anti-HER2 therapy has demonstrated an OS benefit over chemotherapy in 2nd-line, possibly due to loss of HER2 expression following Tras-based therapy. In GEC xenograft models, dual targeting of HER2 with TUC and Tras showed superior activity to either agent alone. Interim results from the MOUNTAINEER study have shown promising activity for TUC and Tras in HER2+ mCRC. The MOUNTAINEER-02 study is evaluating the efficacy and safety of TUC in combination with Tras, ramucirumab (Ram), and paclitaxel (Pac) in pts with HER2+ GEC. Methods: MOUNTAINEER-02 (NCT04499924) is a phase 2/3 study evaluating TUC and Tras with the 2nd-line standard of care, Ram and Pac. Pts receive TUC 300 mg or placebo PO BID, Tras (6 then 4 mg/kg) or placebo (IV on Days 1 and 15 of each 28-day cycle), Pac (IV on Days 1, 8, 15), and Ram (IV on Days 1 and 15). Eligible pts have locally-advanced unresectable or metastatic HER2+ GEC, have received a HER2-directed antibody, and 1 prior line of therapy for advanced disease. Pts must be ≥18 years of age, with an ECOG ≤1, and have had no prior exposure to Ram, anti-HER2 or anti-EGFR TKI, HER2-directed antibody-drug conjugates, or taxanes ≤12 months before enrollment. Due to the potential impact of TUC on Pac metabolism, the study will include an initial Pac dose finding stage. The open-label phase 2 part will determine the recommended dose of Pac (60 or 80 mg/m²) combined with TUC, Tras, and Ram in 6-12 patients, and evaluate the safety and activity of the regimen in Cohorts 2A and 2B (30 patients each). The randomized, double-blind, phase 3 part will compare the efficacy and safety of TUC and Tras (Arm 3A; ~235 patients) vs. placebo (Arm 3B; ~235 patients), both in combination with Ram and Pac, and also evaluate activity of TUC with Ram and Pac (Arm 3C; ~30 patients). The dual primary phase 3 endpoints are OS and PFS per investigator, with confirmed ORR as a key secondary endpoint. HER2 status is determined at baseline using a blood-based NGS assay, and IHC/ISH of fresh or archival tumor biopsies, if available. Pts must be HER2+ by blood-based NGS in Cohort 2A and phase 3; in Cohort 2B, pts must be HER2+ in a biopsy taken post-progression during/after 1st-line therapy, but HER2-negative by blood-based NGS. Disease assessments per RECISTv1.1 will occur q6 weeks for 36 weeks, then q9 weeks. The pharmacokinetics of TUC, Pac, and their metabolites will be evaluated in a subset of pts, including a cohort with gastrectomies. Enrollment is ongoing in the U.S. Clinical trial information: NCT04499924.

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Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

January 20, 2021

Volume

39

Issue

3_suppl

Start / End Page

TPS252 / TPS252

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., Nakamura, Y., Yoshino, T., Catenacci, D. V. T., Janjigian, Y. Y., Barzi, A., … Marshall, J. (2021). MOUNTAINEER-02: Phase II/III study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2+ gastric or gastroesophageal junction adenocarcinoma—Trial in Progress. In Journal of Clinical Oncology (Vol. 39, pp. TPS252–TPS252). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2021.39.3_suppl.tps252
Strickler, John H., Yoshiaki Nakamura, Takayuki Yoshino, Daniel V. T. Catenacci, Yelena Y. Janjigian, Afsaneh Barzi, Tanios S. Bekaii-Saab, et al. “MOUNTAINEER-02: Phase II/III study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2+ gastric or gastroesophageal junction adenocarcinoma—Trial in Progress.” In Journal of Clinical Oncology, 39:TPS252–TPS252. American Society of Clinical Oncology (ASCO), 2021. https://doi.org/10.1200/jco.2021.39.3_suppl.tps252.
Strickler JH, Nakamura Y, Yoshino T, Catenacci DVT, Janjigian YY, Barzi A, et al. MOUNTAINEER-02: Phase II/III study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2+ gastric or gastroesophageal junction adenocarcinoma—Trial in Progress. In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2021. p. TPS252–TPS252.
Strickler, John H., et al. “MOUNTAINEER-02: Phase II/III study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2+ gastric or gastroesophageal junction adenocarcinoma—Trial in Progress.Journal of Clinical Oncology, vol. 39, no. 3_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. TPS252–TPS252. Crossref, doi:10.1200/jco.2021.39.3_suppl.tps252.
Strickler JH, Nakamura Y, Yoshino T, Catenacci DVT, Janjigian YY, Barzi A, Bekaii-Saab TS, Lenz H-J, Lee J, Van Cutsem E, Chung HC, ALSINA M, Siena S, Mayor JG, Palanca-Wessels MC, Feng W, Marshall J. MOUNTAINEER-02: Phase II/III study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2+ gastric or gastroesophageal junction adenocarcinoma—Trial in Progress. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2021. p. TPS252–TPS252.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

January 20, 2021

Volume

39

Issue

3_suppl

Start / End Page

TPS252 / TPS252

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

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