A Study to Investigate Velzatinib Compared With Imatinib in Adult Participants With Previously Untreated Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (StrateGIST Frontline)

NCT07585266 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: 3062932025-524934-24
• Study Type: interventional
• Target: 800
• Locations: 0 countries
• Sites: N/A

Brief Summary

Gastrointestinal Stromal Tumour (GIST) is a soft tissue tumour that develops in the digestive system, most often in the stomach or small intestine. It is caused by changes in certain proteins that cause the cells to grow uncontrollably. Although current treatments may be effective, tumours may stop responding over time, highlighting the need for newer options. This study is evaluating velzatinib (GSK6042981) in participants with newly diagnosed GIST that has spread or cannot be surgically removed. Velzatinib will be compared with imatinib, the standard treatment, to assess whether it can delay disease worsening and is safe and well tolerated.

Conditions

Gastrointestinal Stromal Neoplasms

Keywords

Velzatinib; Imatinib; GIST; Gastrointestinal stromal tumor

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) as assessed by Blinded independent central review (BICR)

  PFS is defined as time from the date of randomization to the date of disease progression or death due to any cause, whichever occurs first.

  Up to approximately 74 months

Secondary Outcomes (16)

• Confirmed Objective Response Rate (ORR) as assessed by BICR

  Up to approximately 75 months

• Overall survival (OS)

  Up to approximately 75 months

• Confirmed ORR as assessed by Investigator assessment

  Up to approximately 75 months

• Time from initial study randomization to second disease progression or death (PFS2)

  Up to approximately 75 months

• PFS as assessed by Investigator assessment

  Up to approximately 75 months

Study Arms (2)

Velzatinib

EXPERIMENTAL

Drug: Velzatinib

Imatinib

EXPERIMENTAL

Drug: Imatinib

Interventions

Imatinib DRUG

Imatinib will be administered

Also known as: GLIVEC / GLEEVEC

Imatinib

Velzatinib DRUG

Velzatinib will be administered

Also known as: GSK6042981

Velzatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the Informed consent form (ICF).
• Has histologically or cytologically confirmed GIST that is metastatic and/or surgically unresectable.
• Has not received prior systemic therapy for their metastatic and/or surgically unresectable GIST.
• Tumor tissue must be provided to the central laboratory. Tumor tissues may be archival (preferred) or obtained from a fresh biopsy acquired for standard of care (biopsies must be collected before randomization).
• Participants must have ≥1 target lesion (TL).
• All participants must use adequate contraception according to local regulations throughout the study and for a specified period after the last dose of study medication (at least 30 days for velzatinib/imatinib, or 15 days for imatinib only, as applicable, or longer if local regulations specify).
• Male participants must either be abstinent or use a male condom (with a recommendation for their female partner to use highly effective contraception). They must also refrain from donating semen.
• Female participants must not be pregnant or breastfeeding.
• Those of non-childbearing potential are eligible without additional contraception.
• Those of childbearing potential must use an acceptable, highly effective contraceptive method and have a negative pregnancy test before starting the study. The investigator will assess their pregnancy risk.
• Is capable of giving signed informed consent as described in the protocol, including compliance with the requirements and restrictions listed in the ICF and in this protocol.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
• Has adequate organ function.

You may not qualify if:

• 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.
• Has any clinically significant gastrointestinal abnormalities that may alter absorption, e.g., malabsorption syndrome or major resection of the stomach and/or bowels.
• Has had any major surgery (minor surgical procedures such as central venous catheter placement and tumor needle biopsy are not considered major surgical procedures) within 14 days of the first dose of study treatment or participants who have not fully recovered from surgery.
• Has any history of prior allogenic or autologous bone marrow transplant or other solid organ transplant. Participants with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met: a) transplant was \[\>100 days\] prior to screening, and b) the participant has no active infection(s) at the time of screening.
• Has known allergy or hypersensitivity to velzatinib or imatinib, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
• Has a history within 6 months prior of clinically significant or uncontrolled cardiac disease, unstable angina, acute myocardial infarction, New York Heart Association Class III or IV congestive heart failure \[New York Heart Association,1994\], or clinically significant arrhythmia not controlled by standard of care therapy, ventricular arrhythmia, cerebrovascular accident or transient ischemic attack and uncontrolled hypertension.
• Has untreated brain or Central nervous system (CNS) metastases or brain/CNS metastases that have progressed \[e.g., evidence of new or enlarging brain metastasis or new neurologic symptoms attributable to brain/CNS metastases\]. Participants with previously treated and clinically stable brain/CNS metastases and who have completed all corticosteroid therapy for ≥2 weeks before randomization are not excluded from participation
• Has ongoing adverse reaction(s) from prior therapy that has (have) not recovered to ≤Grade 1 or to the baseline status preceding prior therapy, (excluding e.g., alopecia, hearing loss, vitiligo, endocrinopathy managed with replacement therapy, and Grade 2 neuropathy) or that the investigator, with the agreement of the sponsor, considers to be not clinically relevant for the tolerability of study intervention in the current clinical study.
• Has any active renal condition (e.g., infection, requirement for dialysis, or any other significant renal condition that could affect the participant's safety).
• Has any serious and/or unstable medical or psychiatric disorder or other condition(s) (including laboratory assessment abnormalities) that could interfere with the participant's safety, obtainment of informed consent, or compliance to the study procedures.
• Has received radiotherapy within 14 days prior to first dose of study treatment.
• Has received any transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including Granulocyte colony-stimulating factor \[G-CSF\], granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 14 days before randomization.
• Is currently enrolled or has participated in any other clinical study involving an investigational study intervention or any other type of medical research before signing ICF.
• Has a positive drug/alcohol screening assessment.
• Has a known Human immunodeficiency virus (HIV) infection and meets at least one of the following criteria:

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Central Study Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718; GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2026
• First Posted: May 13, 2026
• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): August 30, 2032
• Study Completion (Estimated): September 28, 2032
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share