Phase 3
N=17
Tucatinib, Trastuzumab, Ramucirumab, and Paclitaxel Versus Paclitaxel and Ramucirumab in Previously Treated HER2+ Gastroesophageal Cancer
Gastric Adenocarcinoma · Gastroesophageal Junction Adenocarcinoma · Esophageal Adenocarcinoma
Bottom Line
View on ClinicalTrials.gov: NCT04499924 ↗Enrolled (actual)
17
Serious AEs
52.9%
Results posted
Jan 2025
Primary outcome: Primary: Number of Participants With Dose-limiting Toxicities (DLT) During the First Cycle of Treatment — 0; 2 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- tucatinib (Drug); trastuzumab (Drug); ramucirumab (Drug); paclitaxel (Drug); tucatinib placebo (Other); trastuzumab placebo (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Seagen Inc.
- Primary completion
- Apr 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose-limiting Toxicities (DLT) During the First Cycle of Treatment |
0; 2 | — |
| PRIMARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
8; 9 | — |
| PRIMARY Number of Participants With Treatment-emergent Laboratory Abnormalities |
3; 7; 4; 9; 2; 8 | — |
| PRIMARY Number of Participants With Clinically Significant Vital Signs Values |
8; 9; 7; 9; 2; 3 | — |
| PRIMARY Maximum Percentage Change From Baseline in Weight |
0.34; 6.21 | — |
| PRIMARY Number of Participants With Any Dose Modifications |
7; 9; 7; 8; 7; 8 | — |
| SECONDARY Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 By Investigator Assessment |
50.0; 100.0 | — |
| SECONDARY Confirmed ORR Per RECIST v1.1 By Investigator Assessment |
37.5; 100.0 | — |
| SECONDARY Progression-Free Survival (PFS) Per RECIST v1.1 By Investigator Assessment |
4.1; 12.2 | — |
| SECONDARY Duration of Response (DOR) Per RECIST v1.1 By Investigator Assessment |
10.6; 11.0 | — |
| SECONDARY Disease Control Rate (DCR) Per RECIST v1.1 By Investigator Assessment |
87.5; 100.0 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve to the Time of the Last Quantifiable Concentration (AUClast) of Paclitaxel, Tucatinib and Their Metabolites |
4210; 3210; 550; 521; 2810; 3130 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) |
769; 615; 482; 553; 112; 130 | — |
| SECONDARY Time to Maximum Observed Plasma Concentration (Tmax) |
3.5; 3.9; 3.0; 3.9; 1.2; 1.9 | — |
| SECONDARY Trough Concentration (Ctrough) |
71.0; 156; 67.4; 62.0; 9.64; 17.4 | — |
| SECONDARY Metabolite Ratio Based on AUClast (MRAUClast) |
0.0532; 0.0373; 0.0224; 0.0218; 0.0172; 0.0115 | — |
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). 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.
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT04499924). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.