A Study of Velzatinib in Participants With Metastatic and/or Unresectable GIST After Imatinib, Sunitinib, Regorafenib, and Pimitespib

A Phase 2, Single-arm, Multicenter, Open-Label Study of Velzatinib (GSK6042981) in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) After Imatinib, Sunitinib, Regorafenib, and Pimitespib Therapies (StrateGIST J)

The goal of this study is to evaluate the study drug velzatinib (GSK6042981 / IDRX-42) to see whether velzatinib can shrink or control tumors and is safe and tolerated in Japan participants with gastrointestinal tumors (GIST) who progressed or were intolerant to standard therapies.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastrointestinal Neoplasms
• Intervention / Treatment: Drug: Velzatinib

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed GIST that is metastatic and/or surgically unresectable.
• Documented disease progression on or intolerance to imatinib, sunitinib, regorafenib, and pimitespib.
• Documented mutation status of KIT and/or PDGFRA.
• Tumor tissue must be available for retrospective biomarker analysis. The sample may be from archival tissue or a new biopsy.
• Is willing to use adequate contraception male and/or female participants.

Exclusion Criteria:

• Known untreated or active central nervous system metastases.
• Has significant, uncontrolled, or active cardiovascular disease.
• Participants with a known allergy or hypersensitivity to any component of velzatinib. Participants with a history of Stevens-Johnson syndrome on a prior Tyrosine kinase inhibitor (TKI) are excluded.
• Has a malignancy (except disease under study) that has progressed or required active treatment within the past 24 months except for basal cell or squamous cell carcinomas of the skin or in-situ carcinomas [e.g., breast, cervix, bladder] that have been resected with no evidence of metastatic disease.
• Prior treatment with ripretinib or other investigational agents that are currently under clinical development for GIST.
• Is pregnant or breastfeeding.
• Any condition or illness that, in the opinion of the Investigator, might compromise participant safety or interfere with the evaluation of the safety of the study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Velzatinib	Drug: Velzatinib; Velzatinib will be administered.; Other Names: GSK6042981

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed objective response rate (ORR)	ORR is defined as the percent of participants reaching confirmed complete response (CR) or partial response (PR).	Up to 67 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR)	DOR is defined as the time from the date of first documented objective response (confirmed CR or PR) to the date of first documented disease progression (PD) or death due to any cause, whichever comes first.	Up to 156 weeks
Disease control rate for minimum 8-week period (DCR8)	DCR8 is defined as the percent of participants reaching confirmed CR or PR, or stable disease (SD) sustained for a minimum period of 8 weeks.	Up to 156 weeks
Progression free survival (PFS)	PFS is defined as the time from the date of first dose of study treatment to the date of first documented PD or death due to any cause, whichever comes first.	Up to 156 weeks
Overall survival (OS)	OS is defined as the time from the date of first dose of study treatment to the date of death due to any cause.	Up to 156 weeks
Confirmed ORR	ORR is defined as the percent of participants reaching confirmed CR or PR.	Up to 156 weeks
Change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-F17 (EORTC-QLQ-F17)	The EORTC QLQ-F17 is a shorter version of the EORTC QLQ-C30. QLQ-F17 includes the Physical (PF), Role (RF), Emotional (EF), Cognitive (CF) and Social Functioning (SF) scales as well as the Global Health Status/Quality of Life (QL) scale in their original wording. Scores for each scale are averaged and transformed linearly to a score ranging from 0-100. A high score for functional scales and for Global Health Status/QoL represents better functioning ability or HRQoL.	Baseline (Day 1) up to 156 weeks
Change from baseline in EQ-5D-5L score	The EQ-5D-5L is a validated standardised, self-reported instrument for assessing HRQoL across 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 response levels of severity, ranging from no problems to extreme problems. The questionnaire also includes a visual analog scale for self-rated overall health on a scale from 0 (worst imaginable health) to 100 (best imaginable health).	Baseline (Day 1) up to 156 weeks
Plasma concentrations of velzatinib		Up to 156 weeks
Number of participants with treatment emergent adverse events (TEAEs), serious adverse events (SAEs), dose reductions and interruptions and discontinuation of study treatment due to toxicity by severity		Up to 156 weeks

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Estimated): August 31, 2026
• Primary Completion (Estimated): December 13, 2027
• Study Completion (Estimated): August 31, 2029

Study Registration Dates

• First Submitted: July 1, 2026
• First Submitted That Met QC Criteria: July 1, 2026
• First Posted (Actual): July 8, 2026

Study Record Updates

• Last Update Posted (Actual): July 8, 2026
• Last Update Submitted That Met QC Criteria: July 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Gastrointestinal Stromal Tumors (GIST); IDRX-42; GSK6042981; Velzatinib
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors
• Other Study ID Numbers: 309344

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: GSK will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/gsk-patient-level-data-sharing-july2025.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No