Gastric AdenocarcinomaPhase 2/3MOUNTAINEER-02NCT04499924
Tucatinib, Trastuzumab, Ramucirumab, and Paclitaxel Versus Paclitaxel and Ramucirumab in Previously Treated HER2+ Gastroesophageal Cancer
A Phase 2/3 study testing tucatinib, trastuzumab and ramucirumab in people with Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma, run by Seagen Inc. at 48 sites in 6 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma
- What is being tested?
- tucatinib, trastuzumab and ramucirumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 48 sitesin 6 countries
- Study dates
- 22 Mar 2021to 17 Apr 2024
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 15Show fewer
- 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
Who cannot join
- 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 locations and contacts
48 sites in 6 countries.
48 sites in 6 countries
United States30 sites
Rocky Mountain Cancer Centers - Aurora
Aurora, Colorado, 80012
University of Alabama at Birmingham
Birmingham, Alabama, 35249
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 14203
University of Chicago Medical Center
Chicago, Illinois, 60637
Cleveland Clinic - Taussig Cancer Institute
Cleveland, Ohio, 44195
Texas Oncology - Baylor Sammons Cancer Center
Dallas, Texas, 75246
Cancer Centers of Colorado - Denver
Denver, Colorado, 80218
City of Hope National Medical Center
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27710
Oncology Associates of Oregon
Eugene, Oregon, 97401
SCL Health - St. Mary's Hospital & Medical Center
Grand Junction, Colorado, 81501
Holden Comprehensive Cancer Center / University of Iowa
Iowa City, Iowa, 52242
University of Tennessee
Knoxville, Tennessee, 37920
SCL Health Good Samaritan Medical Center Cancer Centers of Colorado
Lafayette, Colorado, 80026
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169
Norton Cancer Institute
Louisville, Kentucky, 40217
Tennessee Oncology-Nashville/Sarah Cannon Research Institute
Nashville, Tennessee, 37203
University of Pennsylvania / Perelman Center for Advanced Medicine
Philadelphia, Pennsylvania, 19104
Mayo Clinic Arizona
Phoenix, Arizona, 85054
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
Minnesota Oncology Hematology P.A.
Saint Paul, Minnesota, 55102
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
Texas Oncology - San Antonio Medical Center
San Antonio, Texas, 78217
UCLA Medical Center / David Geffen School of Medicine
Santa Monica, California, 90404
Arizona Cancer Center / University of Arizona
Tucson, Arizona, 85724
Texas Oncology - Tyler
Tyler, Texas, 75702
Northwest Cancer Specialists, P.C.
Vancouver, Washington, 98684
Lombardi Cancer Center / Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
Lutheran Medical Center - Cancer Centers of Colorado
Wheat Ridge, Colorado, 80033
South Korea8 sites
Dong-A University Hospital
Busan, 49201
Kyungpook National University Chilgok Hospital
Daegu, 41404
Seoul National University Bundang Hospital
Seongnam-si, 13605
Seoul National University Hospital
Seoul, 03080
Severance Hospital, Yonsei University Health System
Seoul, 03722
Asan Medical Center - Oncology
Seoul, 05505
Samsung Medical Center
Seoul, 06351
Ajou University Hospital
Suwon, 16499
Canada3 sites
London Regional Cancer Program, London Health Sciences Centre
London, Ontario, N6A 5W9
Centre Hospitalier de l'Universite de Montreal
Montreal, Quebec, H2X 3E4
McGill University Department of Oncology / McGill University Health Centre
Montreal, Quebec, H4A 3J1
Taiwan3 sites
Kaohsiung Medical University Hospital
Kaohsiung City, 807
National Taiwan University Hospital
Taipei, 10002
Taipei Veterans General Hospital
Taipei, 11217
Australia2 sites
Central Coast Local Health District (Gosford and Wyong Hospitals)
Gosford, 2250
Austin Health
Heidelberg, 63V6 63
United Kingdom2 sites
Sarah Cannon Research Institute UK
London, W3 0ER
The Christie NHS Foundation Trust
Manchester, M20 4BX
About this study
Official 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)
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.
- Conditions
- Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma
- Being tested
- tucatinib, trastuzumab, ramucirumab, paclitaxel, tucatinib placebo
- Keywords
- HER2+, HER2-positive, GEA, GEC, GEJ, Seattle Genetics
- Medical subject headings
- Adenocarcinoma Of Esophagus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tucatinibDrug
Also called TUKYSA, ONT-380, ARRY-380
300 mg given twice daily orally
trastuzumabDrug
6 mg/kg loading dose will be administered intravenously (IV; into the vein) on Cycle 1 Day 1, followed by 4 mg/kg IV on Cycle 1 Day 15 and then Days 1 and 15 of each cycle thereafter
ramucirumabDrug
Also called CYRAMZA
8 mg/kg will be administered IV on Days 1 and 15 of each cycle
paclitaxelDrug
60 or 80 mg/m^2 IV on Days 1, 8, and 15 of each cycle
tucatinib placeboOther
Given twice daily orally
trastuzumab placeboOther
IV on Days 1 and 15 of each cycle
| Study group | Role | What they receive |
|---|---|---|
| Phase 2 Arm | Experimental | Tucatinib + trastuzumab + ramucirumab + paclitaxel Receives: Drug: tucatinib; Drug: trastuzumab; Drug: ramucirumab; Drug: paclitaxel |
| Arm 3A | Experimental | Tucatinib + trastuzumab + ramucirumab + paclitaxel Receives: Drug: tucatinib; Drug: trastuzumab; Drug: ramucirumab; Drug: paclitaxel |
| Arm 3B | Active comparator | Ramucirumab + paclitaxel + tucatinib placebo + trastuzumab placebo Receives: Drug: ramucirumab; Drug: paclitaxel; Other: tucatinib placebo; Other: trastuzumab placebo |
| Arm 3C | Experimental | Tucatinib + ramucirumab + paclitaxel + trastuzumab placebo Receives: Drug: tucatinib; Drug: ramucirumab; Drug: paclitaxel; Other: trastuzumab placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose-limiting Toxicities (DLT) During the First Cycle of Treatment
DLTs were adverse events (AEs), laboratory abnormalities, or treatment modifications that occurred during the first cycle of treatment in the Phase 2 paclitaxel dose optimization stage that were related to paclitaxel, to tucatinib, or to the combination of tucatinib, trastuzumab, ramucirumab and paclitaxel and that met any of the study protocol specified criteria. The relationship of AEs to study drugs was determined by the investigator. AEs that were attributed only to trastuzumab and/or ramucirumab, but not tucatinib or paclitaxel were not considered DLTs.
Measured: Cycle 1 (28 days)
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An AE was any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. AEs were defined as treatment emergent if they were newly occurring or worsened following study treatment. A TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, ramucirumab, or paclitaxel) and up to 30 days after the last dose of study treatment (tucatinib, trastuzumab, ramucirumab, or paclitaxel, whichever was later).
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum treatment duration= 19.8 months, maximum follow-up duration up to 20.8 months)
Number of Participants With Treatment-emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities were defined as abnormalities that are new or worsened on or after receiving the first dose of study treatment up to 30 days after the last dose of study treatment. Laboratory abnormalities included: 1) Blood chemistry: alanine aminotransferase increased, albumin decreased, alkaline phosphatase increased, aspartate aminotransferase increased, calcium corrected for albumin decreased, calcium corrected for albumin increased, creatinine increased, glomerular filtration rate estimated decreased, glucose decreased, lactate dehydrogenase increased, magnesium decreased, magnesium increased, potassium decreased, potassium increased, sodium decreased, sodium increased, and total bilirubin increased; 2) Hematological: hemoglobin decreased, leukocytes decreased, lymphocytes decreased, neutrophils decreased, and platelets decreased.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum treatment duration= 19.8 months, maximum follow-up duration up to 20.8 months)
Number of Participants With Clinically Significant Vital Signs Values
Vital sign examinations included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate. Criteria: SBP greater than or equal to (>=) 120 millimeters of mercury (mm Hg) or DBP >= 80 mm Hg; SBP >= 140 mm Hg or DBP >= 90 mm Hg; SBP >= 160 mm Hg or DBP >= 100 mm Hg), heart rate greater than (>) 100 beats per minute (min). Clinical significance in vital signs abnormalities was judged by investigator. In this outcome measure number of participants with at least 1 clinically significant abnormality in any vital sign are reported.
Measured: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum treatment duration= 19.8 months, maximum follow-up duration up to 20.8 months)
Maximum Percentage Change From Baseline in Weight
Maximum percentage decrease from baseline in weight is reported in this outcome measure.
Measured: From Baseline (Day 1) up to 30 days after the last dose of study treatment (maximum treatment duration= 19.8 months, maximum follow-up duration up to 20.8 months)
Number of Participants With Any Dose Modifications
Dose modification included dose hold, dose reduction, dose error and unplanned dose adjustments. Number of participants with any dose treatment modifications for paclitaxel, ramucirumab, trastuzumab, and tucatinib are reported in this outcome measure.
Measured: From first dose of the study treatment (Day 1) up to the last dose of study treatment (maximum treatment duration up to 19.8 months)
Secondary outcomes (10)
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 By Investigator Assessment
ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) according to RECIST v 1.1 by investigator assessment. As per RECIST v1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR was defined as at least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. As per RECIST v1.1, disease progression (PD) was defined as one of the following: at least a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) with an absolute increase of at least 5mm, unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.
Measured: From the first dose of study treatment until the first documented CR or PR on or before the first documented PD or new anti-cancer therapies or death, whichever occurred first (up to 19.8 months)
Confirmed ORR Per RECIST v1.1 By Investigator Assessment
Confirmed ORR was defined as the percentage of participants with best overall response of confirmed CR or PR according to RECIST v1.1 by investigator assessment. For a response to be confirmed, the subsequent response needs to be at least 4 weeks after the initial response. As per RECIST v1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as at least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. As per RECIST v1.1, disease progression (PD) was defined as one of the following: at least a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) with an absolute increase of at least 5mm, unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.
Measured: From the first dose of study treatment until the first documented confirmed CR or PR or before the first documented PD or new anti-cancer therapies or death, whichever occurred first (up to 19.8 months)
Progression-Free Survival (PFS) Per RECIST v1.1 By Investigator Assessment
PFS was defined as the time from the date of treatment initiation to the date of documented PD or death from any cause, whichever occurred first per RECIST version 1.1 by investigator assessment. As per RECIST v1.1, disease progression (PD) was defined as one of the following: at least a 20% increase in the sum of diameters (SOD) of target lesions (taking as reference the smallest sum on study) with an absolute increase of at least 5mm, unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions. Participants without documentation of PD or death at the time of analysis were censored at the date of the last tumor assessment. Kaplan-Meier method was used for evaluation.
Measured: From the date of first dose until the first documentation of PD or death or censoring date, whichever occurred first (up to 19.8 months)
Duration of Response (DOR) Per RECIST v1.1 By Investigator Assessment
DOR: time from first documentation of objective response of CR or PR to first documentation of PD or death from any cause, whichever occurred first according to RECIST v1.1 by investigator assessment. As per RECIST v1.1, CR: disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. PD was defined as one of the following: at least a 20% increase in sum of diameters of target lesions (taking as reference the smallest sum on study) with an absolute increase of at least 5mm, unequivocal progression of existing non-target lesions, or appearance of one or more new lesions. Participants without documentation of PD or death at time of analysis were censored at the date of last tumor assessment. Kaplan-Meier method was used for evaluation.
Measured: From the first documented CR or PR until the first documentation of PD or death or censoring date, whichever occurred first (up to 19.8 months)
Disease Control Rate (DCR) Per RECIST v1.1 By Investigator Assessment
DCR was defined as percentage of participants with CR, PR, or stable disease (SD or non-CR/non-progressive disease) according to RECIST v1.1 by investigator assessment. As per RECIST v1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as at least a 30 % decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as one of following: at least a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) with an absolute increase of at least 5mm, unequivocal progression of existing non-target lesions, or appearance of one or more new lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum of diameters.
Measured: From the first dose study treatment until PD or death, whichever occurred first (up to 19.8 months)
Area Under the Plasma Concentration-time Curve to the Time of the Last Quantifiable Concentration (AUClast) of Paclitaxel, Tucatinib and Their Metabolites
AUClast was reported for tucatinib, tucatinib metabolite (ONT-993), paclitaxel and paclitaxel metabolites (6 alpha-hydroxy-paclitaxel, 3'-p-hydroxy-paclitaxel and 6 alpha-3'-p-Dihydroxy-paclitaxel).
Measured: Tucatinib and ONT-993- Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 2, 4, 6, 8 hours post-dose; Paclitaxel and its metabolites- Cycle 1 Days 1 and 8, Cycle 2 Day 1: Pre-dose, 2, 4, 6, 8 hours post-dose (each cycle length=28 days)
Maximum Observed Plasma Concentration (Cmax)
Cmax was reported for tucatinib and tucatinib metabolite ONT-993.
Measured: Tucatinib and ONT-993- Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 2, 4, 6, 8 hours post-dose (each cycle length=28 days)
Time to Maximum Observed Plasma Concentration (Tmax)
Tmax was reported for tucatinib and tucatinib metabolite ONT-993.
Measured: Tucatinib and ONT-993- Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 2, 4, 6, 8 hours post-dose (each cycle length=28 days)
Trough Concentration (Ctrough)
Ctrough was calculated for tucatinib and tucatinib metabolite ONT-993.
Measured: Tucatinib and ONT-993- Cycle 1 Day 8, Cycle 2 Day 1: Predose (each cycle length=28 days)
Metabolite Ratio Based on AUClast (MRAUClast)
MRAUClast was defined as metabolic ratio, that is, ratio of the AUClast of a given paclitaxel metabolite over the AUClast of paclitaxel. MRAUClast for 6 alpha-hydroxypaclitaxel, 3-p-hydroxy-paclitaxel and 6 alpha-3-p-dihydroxy-paclitaxel was reported in this outcome measure.
Measured: Paclitaxel and its metabolites- Cycle 1 Days 1 and 8, Cycle 2 Day 1: Pre-dose, 2, 4, 6, 8 hours post-dose (each cycle length=28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2020
- Study start22 Mar 2021
- Primary completion17 Apr 2024
- Study completion17 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Gastric AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seagen Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- JoAl Mayor, PharmD, BCOP, Study director, Seagen Inc.Michelle Ubowski, PharmD, Study director, Seagen Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04499924
- Sponsor's protocol ID
- SGNTUC-022
- Other IDs
- C4251004
- Acronym
- MOUNTAINEER-02
- Status last verified
- Dec 2024
- First submitted
- 31 Jul 2020
- Last updated
- 22 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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)
- ClinicalTrials.gov ID
- NCT04499924
- Acronym / sponsor ID
- MOUNTAINEER-02 / SGNTUC-022
- Conditions
- Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma
- Keywords
- HER2+, HER2-positive, GEA, GEC, GEJ, Seattle Genetics
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Seagen Inc.Industry (pharma, biotech, devices)
- Study start
- 22 Mar 2021 (actual)
- Primary completion
- 17 Apr 2024 (actual)
- Study completion
- 17 Apr 2024 (actual)
- First posted
- 5 Aug 2020 (actual)
- Results
- Posted 22 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase 2 Arm | Experimental | Drug: tucatinib, Drug: trastuzumab, Drug: ramucirumab, Drug: paclitaxelTucatinib + trastuzumab + ramucirumab + paclitaxel |
| Arm 3A | Experimental | Drug: tucatinib, Drug: trastuzumab, Drug: ramucirumab, Drug: paclitaxelTucatinib + trastuzumab + ramucirumab + paclitaxel |
| Arm 3B | Active comparator | Drug: ramucirumab, Drug: paclitaxel, Other: tucatinib placebo, Other: trastuzumab placeboRamucirumab + paclitaxel + tucatinib placebo + trastuzumab placebo |
| Arm 3C | Experimental | Drug: tucatinib, Drug: ramucirumab, Drug: paclitaxel, Other: trastuzumab placeboTucatinib + ramucirumab + paclitaxel + trastuzumab placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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:
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tucatinibAlso: TUKYSA, ONT-380, ARRY-380300 mg given twice daily orally | Drug | Arm 3A, Arm 3C, Phase 2 Arm |
| trastuzumab6 mg/kg loading dose will be administered intravenously (IV; into the vein) on Cycle 1 Day 1, followed by 4 mg/kg IV on Cycle 1 Day 15 and then Days 1 and 15 of each cycle thereafter | Drug | Arm 3A, Phase 2 Arm |
| ramucirumabAlso: CYRAMZA8 mg/kg will be administered IV on Days 1 and 15 of each cycle | Drug | Arm 3A, Arm 3B, Arm 3C, Phase 2 Arm |
| paclitaxel60 or 80 mg/m^2 IV on Days 1, 8, and 15 of each cycle | Drug | Arm 3A, Arm 3B, Arm 3C, Phase 2 Arm |
| tucatinib placeboGiven twice daily orally | Other | Arm 3B |
| trastuzumab placeboIV on Days 1 and 15 of each cycle | Other | Arm 3B, Arm 3C |
Primary outcome
Number of Participants With Dose-limiting Toxicities (DLT) During the First Cycle of Treatment
Time frame: Cycle 1 (28 days)
DLTs were adverse events (AEs), laboratory abnormalities, or treatment modifications that occurred during the first cycle of treatment in the Phase 2 paclitaxel dose optimization stage that were related to paclitaxel, to tucatinib, or to the combination of tucatinib, trastuzumab, ramucirumab and paclitaxel and that met any of the study protocol specified criteria. The relationship of AEs to study drugs was determined by the investigator. AEs that were attributed only to trastuzumab and/or ramucirumab, but not tucatinib or paclitaxel were not considered DLTs.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum treatment duration= 19.8 months, maximum follow-up duration up to 20.8 months)
An AE was any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. AEs were defined as treatment emergent if they were newly occurring or worsened following study treatment. A TEAE was defined as a newly occurring or worsening AE after the first dose of study treatment (tucatinib, trastuzumab, ramucirumab, or paclitaxel) and up to 30 days after the last dose of study treatment (tucatinib, trastuzumab, ramucirumab, or paclitaxel, whichever was later).
Number of Participants With Treatment-emergent Laboratory Abnormalities
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum treatment duration= 19.8 months, maximum follow-up duration up to 20.8 months)
Treatment-emergent laboratory abnormalities were defined as abnormalities that are new or worsened on or after receiving the first dose of study treatment up to 30 days after the last dose of study treatment. Laboratory abnormalities included: 1) Blood chemistry: alanine aminotransferase increased, albumin decreased, alkaline phosphatase increased, aspartate aminotransferase increased, calcium corrected for albumin decreased, calcium corrected for albumin increased, creatinine increased, glomerular filtration rate estimated decreased, glucose decreased, lactate dehydrogenase increased, magnesium decreased, magnesium increased, potassium decreased, potassium increased, sodium decreased, sodium increased, and total bilirubin increased; 2) Hematological: hemoglobin decreased, leukocytes decreased, lymphocytes decreased, neutrophils decreased, and platelets decreased.
Number of Participants With Clinically Significant Vital Signs Values
Time frame: From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (maximum treatment duration= 19.8 months, maximum follow-up duration up to 20.8 months)
Vital sign examinations included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate. Criteria: SBP greater than or equal to (>=) 120 millimeters of mercury (mm Hg) or DBP >= 80 mm Hg; SBP >= 140 mm Hg or DBP >= 90 mm Hg; SBP >= 160 mm Hg or DBP >= 100 mm Hg), heart rate greater than (>) 100 beats per minute (min). Clinical significance in vital signs abnormalities was judged by investigator. In this outcome measure number of participants with at least 1 clinically significant abnormality in any vital sign are reported.
Maximum Percentage Change From Baseline in Weight
Time frame: From Baseline (Day 1) up to 30 days after the last dose of study treatment (maximum treatment duration= 19.8 months, maximum follow-up duration up to 20.8 months)
Maximum percentage decrease from baseline in weight is reported in this outcome measure.
Number of Participants With Any Dose Modifications
Time frame: From first dose of the study treatment (Day 1) up to the last dose of study treatment (maximum treatment duration up to 19.8 months)
Dose modification included dose hold, dose reduction, dose error and unplanned dose adjustments. Number of participants with any dose treatment modifications for paclitaxel, ramucirumab, trastuzumab, and tucatinib are reported in this outcome measure.
10 secondary outcomes
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 By Investigator Assessment
Time frame: From the first dose of study treatment until the first documented CR or PR on or before the first documented PD or new anti-cancer therapies or death, whichever occurred first (up to 19.8 months)
Confirmed ORR Per RECIST v1.1 By Investigator Assessment
Time frame: From the first dose of study treatment until the first documented confirmed CR or PR or before the first documented PD or new anti-cancer therapies or death, whichever occurred first (up to 19.8 months)
Progression-Free Survival (PFS) Per RECIST v1.1 By Investigator Assessment
Time frame: From the date of first dose until the first documentation of PD or death or censoring date, whichever occurred first (up to 19.8 months)
Duration of Response (DOR) Per RECIST v1.1 By Investigator Assessment
Time frame: From the first documented CR or PR until the first documentation of PD or death or censoring date, whichever occurred first (up to 19.8 months)
Disease Control Rate (DCR) Per RECIST v1.1 By Investigator Assessment
Time frame: From the first dose study treatment until PD or death, whichever occurred first (up to 19.8 months)
Area Under the Plasma Concentration-time Curve to the Time of the Last Quantifiable Concentration (AUClast) of Paclitaxel, Tucatinib and Their Metabolites
Time frame: Tucatinib and ONT-993- Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 2, 4, 6, 8 hours post-dose; Paclitaxel and its metabolites- Cycle 1 Days 1 and 8, Cycle 2 Day 1: Pre-dose, 2, 4, 6, 8 hours post-dose (each cycle length=28 days)
Maximum Observed Plasma Concentration (Cmax)
Time frame: Tucatinib and ONT-993- Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 2, 4, 6, 8 hours post-dose (each cycle length=28 days)
Time to Maximum Observed Plasma Concentration (Tmax)
Time frame: Tucatinib and ONT-993- Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 2, 4, 6, 8 hours post-dose (each cycle length=28 days)
Trough Concentration (Ctrough)
Time frame: Tucatinib and ONT-993- Cycle 1 Day 8, Cycle 2 Day 1: Predose (each cycle length=28 days)
Metabolite Ratio Based on AUClast (MRAUClast)
Time frame: Paclitaxel and its metabolites- Cycle 1 Days 1 and 8, Cycle 2 Day 1: Pre-dose, 2, 4, 6, 8 hours post-dose (each cycle length=28 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
JoAl Mayor, PharmD, BCOP study director
Seagen Inc.
Michelle Ubowski, PharmD study director
Seagen Inc.
48 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing tucatinib, trastuzumab and ramucirumab in people with Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma, run by Seagen Inc. at 48 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 48 sites in United States, South Korea, Canada, Taiwan, Australia and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose-limiting Toxicities (DLT) During the First Cycle of Treatment (time frame: Cycle 1 (28 days)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2025.