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

C4251004 (Other Identifier)

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