Combining regorafenib and envafolimab for advanced gastrointestinal tumors with specific mutations

A Phase II, Open Controlled, Clinical Study of Regorafenib Combined with Envafolimab for Metastatic Gastrointestinal Stromal Tumors with Kit Gene Exon 17 Mutation That Failed Standard Treatment

This study is testing if a combination of two drugs, regorafenib and envafolimab, can help people with advanced gastrointestinal tumors that have a specific mutation and haven’t responded to other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 82 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Peking University (Academic / other)
• Drugs / interventions: imatinib, sunitinib, ripretinib, envafolimab, immunotherapy
• Locations: 1 site (Beijing, Beijing)
• Trial ID: NCT06772233 on ClinicalTrials.gov

What this trial studies

This multicenter, prospective, randomized controlled Phase II clinical trial evaluates the efficacy and safety of regorafenib combined with envafolimab in patients with metastatic gastrointestinal stromal tumors (GIST) that have a KIT exon 17 mutation and have failed standard treatments. The study aims to compare this combination therapy against previously effective maintenance regimens. Patients will be randomly assigned to either the treatment group or the control group, with imaging assessments conducted every two months to monitor progress. A total of 82 patients are expected to be enrolled in this trial.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with pathologically confirmed metastatic GIST harboring a KIT exon 17 mutation who have experienced progression or intolerance after standard treatments.

Not a fit: Patients with GIST that do not have a KIT exon 17 mutation or those who have not failed standard treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced GIST who have limited treatment alternatives.

How similar studies have performed: While this approach is novel in combining regorafenib and envafolimab for this specific mutation, similar studies have shown promise in targeting GIST with other therapies.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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);
* Subjects deemed by the investigator to be unable or unwilling to comply with the study protocol requirements.

Where this trial is running

Beijing, Beijing

• Beijing Cancer Hospital, 52 Fucheng Road — Beijing, Beijing, China (Recruiting)

Study contacts

• Principal investigator: Jian Li, Dr. — Peking University Cancer Hospital & Institute
• Study coordinator: Jian Li, Dr.

Conditions Metastatic Gastrointestinal Stromal Tumors; gastrointestinal stromal tumors, KIT exon 17 mutations