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No longer recruiting (closed or complete)Last updated: 11 April 2024

MOUNTAINEER-02: This phase II/III study is trying to understand whether a combined treatment of three targeted therapies (tucatinib, trastuzumab and ramucirumab) and chemotherapy (paclitaxel), works better than one targeted therapy (ramucirumab) and chemotherapy (paclitaxel) to treat HER-2 positive cancers of the stomach and oesophagusA Randomized, Double-blind, Placebo-controlled, Active Comparator Phase 2/3 Study of Tucatinib in Combination With Trastuzumab, Ramucirumab, and Paclitaxel in Subjects With Previously Treated, Locally-advanced Unresectable or Metastatic HER2+ Gastric or Gastroesophageal Junction Adenocarcinoma (GEC)

Trial purpose

Medical clipboardCancer treatment

Tumor type

Upper gastrointestinal tract Cancers Upper gastrointestinal tract

Age

People18+

Trial acronym

MOUNTAINEER-02

Clinical summary

Summary

In the Phase 2 part of the trial, participants and their doctors will know what drugs are being given (open-label). In the Phase 3 part, the study is "blinded." This means that participants, their doctor, and the study sponsor will not know which drugs are being given. Participants will be randomised into one of four arms. In the Phase 2 Arm (experimental), participants will receive tucatinib + trastuzumab + ramucirumab + paclitaxel. Tucatinib will be administered orally, twice daily at a dose of 300mg. Trastuzumab will be administered intravenously (via IV) at a dose of 6mg/kg on Cycle 1 Day 1, followed by 4mg/kg on Cycle 1 Day 15 and then Days 1 and 15 of each cycle thereafter. Ramucirumab will be administered via IV at a dose of 8mg/kg on Days 1 and 15 of each cycle. Paclitaxel will be administered via IV at a dose of 60 or 80mg/m^2 on Days 1, 8 and 15 of each cycle. In Phase 3 Arm A (experimental), participants will also receive tucatinib + trastuzumab + ramucirumab + paclitaxel, all administered the same as the Phase 2 Arm. In Phase 3 Arm B (active comparator), participants will receive Ramucirumab + paclitaxel + tucatinib placebo + trastuzumab placebo. Ramucirumab will be administered via IV at a dose of 8mg/kg on Days 1 and 15 of each cycle. Paclitaxel will be administered at a dose of 60 or 80mg/m^2 via IV on days 1, 8 and 15 of each cycle. The tucatinib placebo will be given twice daily, orally, and the trastuzumab placebo will be given via IV on Days 1 and 15 of each cycle. In Phase 3 Arm C (experimental), participants will receive Tucatinib + ramucirumab + paclitaxel + trastuzumab placebo. Tucatinib will be given twice daily, orally, at a dose of 300mg. Ramucirumab will be administered via IV at a dose of 8mg/kg on Days 1 and 15 of each cycle. Paclitaxel will be administered via IV at a dose of 60 or 80 on Days 1, 8 and 15 of each cycle. The Trastuzumab placebo will be given via IV on Days 1 and 15 of each cycle.

Conditions

This trial is treating people with locally advanced or metastatic cancers of the stomach and oesophagus

Eligibility

Inclusion

  • Histologically or cytologically confirmed diagnosis of locally-advanced unresectable or metastatic HER2+ gastric or gastroesophageal junction adenocarcinoma (GEC)
  • HER2+ disease documented since progression of the most recent line of systemic therapy, as follows:

    • Phase 2 paclitaxel dose optimization stage:

      • HER2 amplification in a blood-based NGS assay performed at a central laboratory, or
      • HER2 overexpression/amplification immunohistochemistry (IHC) and in situ hybridization (ISH) (IHC3+ or IHC2+/ISH+) assay of a tumor tissue sample
    • Phase 2 dose expansion stage:

      • Cohort 2A: HER2 amplification in a blood-based NGS assay performed at a central laboratory
      • Cohort 2B: No HER2 amplification by blood-based NGS assay, but HER2 overexpression/amplification by IHC and ISH (IHC3+ or IHC2+/ISH+) assay of a tumor tissue sample
    • Phase 3: HER2 amplification in a blood-based NGS assay performed at a central laboratory
  • History of prior treatment with a HER2-directed antibody
  • Progressive disease during or after first-line therapy for locally-advanced unresectable or metastatic GEC
  • Phase 2: Measurable disease according to RECIST version 1.1
  • Phase 3: Measurable or non-measurable disease according to RECIST version 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
  • Life expectancy of at least 3 months, in the opinion of the investigator

Exclusion

  • Subjects with squamous cell or undifferentiated GEC
  • Having received more than 1 line of prior systemic therapy for locally-advanced unresectable or metastatic disease
  • Having received taxanes ≤12 months prior to enrollment, prior treatment with ramucirumab, or prior treatment with tucatinib, lapatinib, neratinib, afatinib, or any other investigational anti-HER2 and/or anti-EGFR tyrosine kinase inhibitor, or with T-DM1, T-Dxd, or any other HER2-directed antibody-drug conjugate
  • Phase 2 paclitaxel dose optimization stage only: history of prior partial or total gastrectomy
  • Unable to swallow pills

Inclusion

  • You are able to swallow medication by mouth.
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • Your cancer has not spread to other parts of the body (localised).
  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

Participating hospitals

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:

Trial sponsor

Seagen Inc.

Scientific Title

A Randomized, Double-blind, Placebo-controlled, Active Comparator Phase 2/3 Study of Tucatinib in Combination With Trastuzumab, Ramucirumab, and Paclitaxel in Subjects With Previously Treated, Locally-advanced Unresectable or Metastatic HER2+ Gastric or Gastroesophageal Junction Adenocarcinoma (GEC)

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