ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Phase Ib Trial of the Combination of Imatinib and Binimetinib in Patients with Advanced Gastrointestinal Stromal Tumors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 14 citations in OpenAlex.
- Fibroblast growth factor receptor inhibition for succinate dehydrogenase-deficient gastrointestinal stromal tumors: a phase 2 trial.Nature medicine · 2026Trial
- ctDNA as a Molecular Biomarker in the Phase II Trial of Imatinib plus Binimetinib in Patients with Advanced Gastrointestinal Stromal Tumor.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Precision therapeutic strategies for advanced gastrointestinal stromal tumors.Cancer metastasis reviews · 2026Review
- Article
- Molecular classification identifies aggressive gastrointestinal stromal tumor subtype targetable by PARP inhibitors.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Gastrointestinal Stromal Tumor: History, Molecular Subtypes, and Risk Stratification.Journal of gastric cancer · 2026Review
- Targeted Therapy for Advanced Gastrointestinal Stromal Tumors: Evolution and Future Directions.Drug design, development and therapy · 2026Review
- The Mechanisms of Imatinib Resistance in Gastrointestinal Stromal Tumours: Theoretical Basis and Therapeutic Aspect.Journal of cellular and molecular medicine · 2025Review
- Regulatory roles of non-coding RNAs in programmed cell death pathways and drug resistance in gastrointestinal stromal tumors.Clinical and experimental medicine · 2025Review
- Dropped head syndrome suspected due to oxaliplatin used in adjuvant chemotherapy for gastric cancer: a case report.Surgical case reports · 2024Article
- Molecular characteristics and immune microenvironment of gastrointestinal stromal tumours: targets for therapeutic strategies.Frontiers in oncology · 2024Review
- Microwave ablation for painful chest wall metastases from gastrointestinal stromal tumor: a case report.Frontiers in oncology · 2024Article
- Molecular Advances in the Treatment of Advanced Gastrointestinal Stromal Tumor.The oncologist · 2023Review
- Current status of and future prospects for the treatment of unresectable or metastatic gastrointestinal stromal tumours.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2023Review
- New treatment strategies for advanced-stage gastrointestinal stromal tumours.Nature reviews. Clinical oncology · 2022Review
Corrections and comments
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Authors and funding
24 authors at 1 institution in 1 country.
Funding
Abstract
purposeThis phase Ib trial was designed to evaluate the safety and early efficacy signal of the combination of imatinib and binimetinib in patients with imatinib-resistant advanced gastrointestinal stromal tumors (GISTs). PATIENTS AND
methodsThis trial used a standard 3 + 3 design to determine the recommended phase II dose (RP2D). Additional patients were enrolled on an expansion cohort at the RP2D enriching for succinate dehydrogenase (SDH)-deficient GISTs to explore potential efficacy.
resultsThe trial enrolled nine patients in the dose-escalation cohort and 14 in the dose-expansion cohort including six with SDH-deficient GISTs. Imatinib 400 mg daily with binimetinib 45 mg twice daily was established as the RP2D. Dose-limiting toxicity (DLT) was asymptomatic grade 4 creatinine phosphokinase (CPK) elevation. The most common non-DLT grade 3/4 toxicity was asymptomatic CPK elevation (69.6%). Other common ≥grade 2 toxicities included peripheral edema (17.4%), acneiform rash (21.7%), anemia (30.4%), hypophosphatemia (39.1%), and aspartate aminotransferase (AST) increase (17.4%). Two serious adverse events occurred (grade 2 dropped head syndrome and grade 3 central retinal vein occlusion). No unexpected toxicities were observed. Limited clinical activity was observed in KIT-mutant GIST. For SDH-deficient GISTs, one of five had confirmed RECIST1.1 partial response (PR). The median progression-free survival (mPFS) in patients with SDH-deficient GIST was 45.1 months [95% confidence interval (CI), 15.8-not estimable (NE)]; the median overall survival (mOS) was not reached (95% CI, 31.6 months-NE). One patient with a refractory metastatic SDH-deficient GIST had an exceptional pathologic response and durable clinical benefit.
conclusionsThe combination of imatinib and binimetinib is safe with manageable toxicity and has encouraging activity in SDH-deficient but not imatinib-refractory KIT/PDGFRA-mutant GISTs. The observed clinical benefits provide a motivation for a larger trial of the combination strategy in SDH-deficient GISTs.
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