Comparing Regorafenib Combined With Envafolimab to Physician's Choice in Patients With Metastatic Gastrointestinal Stromal Tumors Harboring KIT Exon 17 Mutations Refractory to Standard Treatment

NCT07559864 | Recruiting Phase 2 DMC

• 1 other identifier: GIST006
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Gastrointestinal stromal tumors (GISTs) are mostly driven by c-kit or PDGFRA mutations, and commonly occur in the stomach and small intestine. Targeted therapy is the mainstay for advanced metastatic GISTs, but there is a lack of effective regimens after drug resistance. Immune checkpoint inhibitors (ICIs) have limited efficacy as monotherapy, while tyrosine kinase inhibitor (TKI) drugs such as regorafenib can improve the immune microenvironment and exert a synergistic effect when combined with ICIs, with more significant efficacy especially in cases with kit exon 17 mutations. This study aims to explore the effectiveness of regorafenib combined with envafolimab in metastatic gastrointestinal stromal tumors with kit exon 17 mutations that have failed standard treatment.

Conditions

GIST - Gastrointestinal Stromal Tumor; KIT Gene Mutation

Keywords

Gastrointestinal Stromal Tumor; Treatment; kit gene

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival（PFS）

  Defined as the time from date of study treatment to disease progression radiological/clinical or death due to any cause, whichever occurs first.

  Up to 2 years

Study Arms (2)

control group（physician-selected）

ACTIVE COMPARATOR

Physicians will make selections based on previous drug tolerance, genetic types, etc.: 1) Maintenance treatment with the original dose of previously effective TKIs: during the previous treatment, the patient had achieved at least stable disease (SD) or partial response (PR), with progression-free survival (PFS) exceeding 6 months and tolerable adverse reactions; 2) Combination therapy with two TKI targeted drugs: according to different action targets indicated by genetic testing of the patient's tissue or peripheral blood, different drugs will be selected for maintenance, or a combination of previously effective and well-tolerated drugs will be chosen, or combination therapy will be selected with reference to previous tolerance.

Drug: physician-selected treatment

treatment group（Regorafenib + Envafolimab）

EXPERIMENTAL

Patients in the treatment group will receive regorafenib combined with envafolimab. Regorafenib: 120 mg, orally, once daily, administered for 3 weeks followed by 1 week of rest. Envafolimab: 200 mg, subcutaneously injected, once every 2 weeks.

Drug: Regorafenib + Envafolimab

Interventions

physician-selected treatment DRUG

physician-selected treatment

control group（physician-selected）

Regorafenib + Envafolimab DRUG

Regorafenib: 120mg, orally, qd, administered for 3 weeks followed by 1 week of rest. Envafolimab: 200mg, subcutaneously injected, q21d.

treatment group（Regorafenib + Envafolimab）

Eligibility Criteria

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

You may qualify if:

• Aged ≥ 18 years, regardless of gender;
• Confirmed as gastrointestinal stromal tumor by histopathological examination;
• Having at least one measurable target lesion meeting the criteria of mRECIST v1.1 (non-lymph node lesions with a long axis ≥ 1.0 cm or a long axis ≥ the thickness of 2 slides); imaging assessment should be performed within 14 days before the first medication;
• Disease progression or intolerance after treatment with imatinib, sunitinib, regorafenib, or ripretinib;
• Primary or secondary KIT exon 17 mutation detected by genetic testing;
• Sufficient organ and bone marrow function, defined as follows: Blood routine: Absolute neutrophil count (ANC) ≥ 1.5×10⁹/L; platelet count (PLT) ≥ 75×10⁹/L; hemoglobin (HGB) ≥ 9.0 g/dL. No use of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), red blood cell transfusion, or platelet transfusion within 14 days before the examination; Liver and kidney function: For subjects without liver metastasis, serum total bilirubin (TBIL) ≤ 1.5×upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN. For subjects with liver metastasis: TBIL ≤ 1.5×ULN; ALT and AST ≤ 5×ULN. Renal function: Serum creatinine (Scr) ≤ 1.5×ULN; Sufficient coagulation function, defined as international normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5×ULN; if the subject is receiving anticoagulant therapy, it is acceptable as long as PT is within the range specified for the anticoagulant drug;
• Provide 15 paraffin-embedded tissue sections before enrollment for immune microenvironment detection;
• ECOG PS score of 0-2;
• Signed informed consent form.

You may not qualify if:

• A history of intolerance to regorafenib treatment, or previous receipt of immune checkpoint inhibitor therapy;
• Being in pregnancy or lactation;
• Those with an expected survival period of less than 3 months;
• Those who have undergone major surgery or suffered significant trauma within 4 weeks before the first blood collection during the screening period, or are expected to require major surgery during the study period;
• Patients with current active ulcers or gastrointestinal bleeding;
• A history of interstitial lung disease or non-infectious pneumonia; a history of active tuberculosis;
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
• Patients with clinically confirmed autoimmune diseases; those with positive HIV or HCV; those with HBV-DNA exceeding the laboratory normal range; those with acute CMV infection;
• Patients with clinically confirmed central nervous system metastases;
• Patients with other malignant tumors within 5 years;
• Immunosuppressed subjects, including those with known immunodeficiency; those currently receiving systemic steroid medications (except those who have used inhaled steroids recently or currently);
• Uncontrolled hypertension: After active antihypertensive treatment, three consecutive blood pressure measurements indicate systolic blood pressure ≥ 160 mmHg and diastolic blood pressure ≥ 100 mmHg;
• Subjects who, in the investigator's assessment, are unable or unwilling to comply with the requirements of the study protocol.

Sponsors & Collaborators

• Jian Li: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100101, China

RECRUITING

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors; Piebaldism

Interventions

regorafenib; envafolimab

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; Albinism; Eye Diseases, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Skin Diseases, Genetic; Hypopigmentation; Pigmentation Disorders; Skin Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Jian Li, MD

  Peking University Cancer Hospital & Institute

  STUDY CHAIR

Central Study Contacts

Jian Li, MD

CONTACT

+86 010 88196561; oncogene@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: April 20, 2026
• First Posted: April 30, 2026
• Study Start: July 14, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

CN (1)