ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Phase Ib/II Trial of Ribociclib in Combination with Binimetinib in Patients with NRAS-mutant Melanoma.
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. It is linked to trial NCT01781572 (A Phase Ib/II, Multicenter, Open Label, Study of LEE011 in Combination With MEK162 in Adult Patients With NRAS Mutant Melanoma), which is not on this map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
A Phase Ib/II, Multicenter, Open Label, Study of LEE011 in Combination With MEK162 in Adult Patients With NRAS Mutant Melanoma
Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Hematological Toxicities in the Modern Era of Melanoma Therapy.Journal of clinical medicine · 2026Review
- Review
- CDK4/6 Inhibitor-Induced Senescence in Cancer: Mechanisms and Therapeutic Implications.Cancers · 2026Review
- Co-targeting CDK4/6 and MEK reverses mesenchymal transition in therapy-refractory BRAF-altered pediatric high-grade glioma.Journal of experimental & clinical cancer research : CR · 2026Article
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- MEK5/ERK5 inhibition sensitizes NRAS-mutant melanoma to MAPK-targeted therapy by preventing Cyclin D/CDK4-mediated G1/S progression.Cell death & disease · 2025Article
- [New systemic treatment approaches for conjunctival melanoma].Die Ophthalmologie · 2025Review
- Genomic profiling and personalized treatment strategies for skin malignancies: findings from the center for cancer genomics and advanced therapeutics database.International journal of clinical oncology · 2025Review
- Review
- Review
- Exploring the pathway: clinical utility and open challenges of targeting BRAF alterations in biliary tract cancers and gastrointestinal malignancies.ESMO gastrointestinal oncology · 2025Review
- The Absorption, Distribution, Metabolism, and Excretion of Binimetinib Following a Single Oral Dose of [Pharmacology research & perspectives · 2025Article
- Case Report: Dupilumab therapy for immune checkpoint inhibitor-induced bullous pemphigoid enables dual immunotherapy initiation in progressive malignant melanoma.Frontiers in oncology · 2025Article
- Combined treatment with CDK4/6, CDK2, and CXCR1/2 inhibitors effectively halts the growth of BRAF wild-type melanoma tumors.Frontiers in oncology · 2025Article
- Genetic Characteristics of Cutaneous, Acral, and Mucosal Melanoma in Japan.Cancer medicine · 2024Article
- Molecularly matched targeted therapy: a promising approach for refractory metastatic melanoma.The oncologist · 2024Article
- Identification of novel disulfidptosis-related lncRNA signatures to predict the prognosis and immune microenvironment of skin cutaneous melanoma patients.Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) · 2024Article
- BRAF - a tumour-agnostic drug target with lineage-specific dependencies.Nature reviews. Clinical oncology · 2024Review
- A real-world study of adjuvant anti-PD -1 immunotherapy on stage III melanoma with BRAF, NRAS, and KIT mutations.Cancer medicine · 2023Article
- Pathology and Molecular Biology of Melanoma.Current issues in molecular biology · 2023Review
Corrections and comments
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Authors and funding
15 authors at 12 institutions in 5 countries.
Funding
Abstract
purposeEnhanced MAPK pathway signaling and cell-cycle checkpoint dysregulation are frequent in NRAS-mutant melanoma and, as such, the regimen of the MEK inhibitor binimetinib and the selective CDK4/6 inhibitor ribociclib is a rational combination. PATIENTS AND
methodsThis is a phase Ib/II, open-label study of ribociclib + binimetinib in patients with NRAS-mutant melanoma (NCT01781572). Primary objectives were to estimate the MTD/recommended phase II dose (RP2D) of the combination (phase Ib) and to characterize combination antitumor activity at the RP2D (phase II). Tumor genomic characterization and pharmacokinetics/pharmacodynamics were also evaluated.
resultsTen patients (16.4%) experienced dose-limiting toxicities in cycle 1 of phase Ib. Overall response rate in the phase II cohort (n = 41) for the selected RP2D (binimetinib 45 mg twice daily + ribociclib 200 mg once daily, 21 days on/7 days off) was 19.5% [8/41; 95% confidence interval (CI), 8.8-34.9]. The response rate was 32.5% (13/40; 95% CI, 20.1-48.0) in patients with NRAS mutation with concurrent alterations of CDKN2A, CDK4, or CCND1. Median progression-free survival was 3.7 months (95% CI, 3.5-5.6) and median overall survival was 11.3 months (95% CI, 9.3-14.2) for all patients. Common treatment-related toxicities included creatine phosphokinase elevation, rash, edema, anemia, nausea, diarrhea, and fatigue. Pharmacokinetics and safety were consistent with single-agent data, supporting a lack of drug-drug interaction.
conclusionsRibociclib + binimetinib can be safely administered and is clinically active in patients with NRAS-mutant melanoma. Co-mutations of cell-cycle genes may define a population with greater likelihood of treatment benefit. See related commentary by Moschos, p. 2977.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.