A Study of Regorafenib Combined With Envafolimab for Metastatic Gastrointestinal Stromal Tumors With Kit Gene Exon 17 Mutation That Failed Standard Treatment

NCT06772233 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: GIST 006
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a multicenter, prospective, randomized controlled Phase II clinical trial. The primary endpoint is to evaluate the efficacy and safety of regorafenib combined with envafolimab compared to physician's choice in patients with metastatic gastrointestinal stromal tumors harboring KIT exon 17 mutations who have failed standard treatments.

Conditions

Metastatic Gastrointestinal Stromal Tumors (GIST)

Keywords

gastrointestinal stromal tumors, KIT exon 17 mutations

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Assessed by the investigator according to mRECIST 1.1 criteria

  From enrollment to disease progression or death, whichever came first, assessed up to 2 years

Secondary Outcomes (3)

• Overall Survival (OS)

  Overall Survival (OS): from enrollment to death, assessed up to 2 years

• Objective Response Rate (ORR)

  assessed up to 2 years

• Incidence of Treatment-Emergent Adverse Events (TEAEs)

  assessed up to 2 years

Other Outcomes (1)

• Exploratory Study Endpoints-Correlation between the immune microenvironment of GIST and the efficacy of immunotherapy.

  From enrollment to the end of the study, assessed up to 2 years

Study Arms (2)

regorafenib combined with envafolimab

EXPERIMENTAL

* Regorafenib: Specification: 40 mg/tablet Dosage: 120 mg, taken orally once daily for 3 weeks, followed by 1 week off, until disease progression or intolerable toxicity occurs. * Envafolimab: Specification: 200 mg/vial Dosage: 200 mg, administered via subcutaneous injection once every 2 weeks, until disease progression or intolerable toxicity occurs.

Drug: regorafenib combined with envafolimab

Physician's choice

ACTIVE COMPARATOR

The governing principle for physician decision-making in the control group was selection based on prior medication tolerability, genotype, etc.: 1. Continued maintenance therapy with the originally effective TKI at the same dose: The patient achieved at least stable disease (SD) or partial response (PR) during prior treatment, with progression-free survival (PFS) exceeding 6 months, and the adverse reactions were tolerable. 2. Combination therapy with two TKIs: Different drugs were selected for maintenance based on distinct actionable mutations identified in the patient's tissue or peripheral blood genetic testing, OR a combination of drugs previously effective and well-tolerated was used, OR the combination therapy was chosen by referencing past tolerability.

Drug: Control Group

Interventions

regorafenib combined with envafolimab DRUG

-Regorafenib: Specification: 40 mg/tablet Dosage: 120 mg, taken orally once daily for 3 weeks, followed by 1 week off, until disease progression or intolerable toxicity occurs. * Envafolimab: Specification: 200 mg/vial Dosage: 200 mg, administered via subcutaneous injection once every 2 weeks, until disease progression or intolerable toxicity occurs.

regorafenib combined with envafolimab

Control Group DRUG

The governing principle for physician decision-making in the control group was selection based on prior medication tolerability, genotype, etc.: a. Continued maintenance therapy with the originally effective TKI at the same dose: The patient achieved at least stable disease (SD) or partial response (PR) during prior treatment, with progression-free survival (PFS) exceeding 6 months, and the adverse reactions were tolerable. b. Combination therapy with two TKIs: Different drugs were selected for maintenance based on distinct actionable mutations identified in the patient's tissue or peripheral blood genetic testing, OR a combination of drugs previously effective and well-tolerated was used, OR the combination therapy was chosen by referencing past tolerability.

Physician's choice

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years, no gender restriction;
• Pathologically confirmed gastrointestinal stromal tumor (GIST);
• At least one measurable target lesion according to mRECIST v1.1 criteria (non-lymph node lesion with a long axis ≥ 1.0 cm or long axis ≥ 2 slide thicknesses); imaging assessment within 14 days before the first dose;
• Progression or intolerance after treatment with imatinib, sunitinib, regorafenib, or ripretinib;
• Genetic testing includes primary or secondary KIT exon 17 mutation;
• Adequate organ and bone marrow function, defined as follows:
• Hematology: Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L; platelet count (PLT) ≥ 75 × 10\^9/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 testing; Liver and kidney function: For patients without liver metastasis, total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN. For patients with liver metastasis: TBIL ≤ 1.5 × ULN; ALT and AST ≤ 5 × ULN. Kidney function: serum creatinine (Scr) ≤ 1.5 × ULN; Adequate coagulation function, defined as international normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5 × ULN; if the patient is on anticoagulant therapy, PT should be within the intended range of the anticoagulant;
• Provide 15 paraffin-embedded tissue sections before enrollment for immune microenvironment testing;
• ECOG PS score 0-2;
• Signed informed consent.

You may not qualify if:

• Unable to tolerate previous regorafenib treatment or previously received immune checkpoint inhibitors;
• Pregnant or breastfeeding;
• Expected survival less than 3 months;
• Underwent major surgery or experienced significant trauma within 4 weeks before the first blood draw during the screening period, or expected to need major surgery during the study;
• Currently have active ulcers or gastrointestinal bleeding;
• History of interstitial lung disease or non-infectious pneumonia; history of active tuberculosis;
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
• Clinically diagnosed autoimmune disease; HIV or HCV positive; HBV-DNA exceeding laboratory normal range; acute CMV infection;
• Patients with central nervous system metastasis;
• Patients with other malignancies within the past five years;
• Immunosuppressed subjects, including those with known immunodeficiency; currently using systemic steroids (except for recent or current use of inhaled steroids);
• Uncontrolled hypertension: Despite aggressive antihypertensive therapy, sequential measurements show systolic blood pressure ≥160 mmHg and diastolic blood pressure ≥100 mmHg on three consecutive occasions;
• Subjects deemed by the investigator to be unable or unwilling to comply with the study protocol requirements.

Sponsors & Collaborators

• Peking University: lead

Study Sites (1)

Beijing Cancer Hospital, 52 Fucheng Road

Beijing, Beijing Municipality, 100142, China

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

envafolimab; Control Groups

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)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Jian Li, Dr.

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jian Li, Dr.

CONTACT

+861088196088; 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

Study Record Dates

• First Submitted: December 30, 2024
• First Posted: January 13, 2025
• Study Start: July 30, 2025
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2028
• Last Updated: July 31, 2025

Record last verified: 2025-07

Locations

CN (1)