Tucatinib, Trastuzumab, Ramucirumab, and Paclitaxel Versus Paclitaxel and Ramucirumab in Previously Treated HER2+ Gastroesophageal Cancer (MOUNTAINEER-02)

Seagen

Status and phase: Completed; Phase 3; Phase 2

Conditions: Esophageal Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Gastric Adenocarcinoma

Treatments: Drug: paclitaxel; Other: tucatinib placebo; Other: trastuzumab placebo; Drug: tucatinib; Drug: trastuzumab; Drug: ramucirumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04499924

SGNTUC-022

Details and patient eligibility

About

This study is being done to see if tucatinib with trastuzumab, ramucirumab and paclitaxel works better than ramucirumab and paclitaxel to treat HER2-positive (HER2+) cancer of the gut (stomach or gastroesophageal cancer). This study will also look at what side effects happen when participants take this combination of drugs. A side effect is anything the drug does other than treating cancer.

Study treatment will be given in 28-day cycles.

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.

Enrollment: 17 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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 criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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17 participants in 4 patient groups

Phase 2 Arm

Experimental group

Description:

Tucatinib + trastuzumab + ramucirumab + paclitaxel

Treatment:

Drug: ramucirumab

Drug: trastuzumab

Drug: tucatinib

Drug: paclitaxel

Arm 3A

Experimental group

Description:

Tucatinib + trastuzumab + ramucirumab + paclitaxel

Treatment:

Drug: ramucirumab

Drug: trastuzumab

Drug: tucatinib

Drug: paclitaxel

Arm 3B

Active Comparator group

Description:

Ramucirumab + paclitaxel + tucatinib placebo + trastuzumab placebo

Treatment:

Drug: ramucirumab

Other: trastuzumab placebo

Other: tucatinib placebo

Drug: paclitaxel

Arm 3C

Experimental group

Description:

Tucatinib + ramucirumab + paclitaxel + trastuzumab placebo

Treatment:

Drug: ramucirumab

Drug: tucatinib

Other: trastuzumab placebo

Drug: paclitaxel