Mektovi (binimetinib) / Ono Pharmaceutical, Pierre Fabre, Pfizer, Medison - LARVOL DELTA

BECOME-MB: Binimetinib Encorafenib Pembrolizumab +/- Stereotactic Radiosurgery in BRAFV600 Melanoma With Brain Metastasis (clinicaltrials.gov) - P2 | N=10 | Active, not recruiting | Sponsor: UNICANCER | Trial completion date: Apr 2029 ➔ Mar 2026 | Trial primary completion date: Apr 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF

A study to learn how well the combination of encorafenib and binimetinib works and how safe it is in adults with thyroid cancer: a plain language summary. (PubMed, Future Oncol) - "[Figure: see text]."

Journal • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma

Phase I Trial of Binimetinib Plus Hydroxychloroquine in Patients with Previously Treated Metastatic Pancreatic Cancer. (PubMed, Oncologist) - P1 | "The combination of BINI + HCQ demonstrated a challenging toxicity profile and limited clinical activity in patients with chemorefractory metastatic PDAC."

Journal • P1 data • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Renal Disease • Solid Tumor • KRAS

Network-based discovery of tumor-checkpoint inverter drugs targeting pancreatic ductal adenocarcinoma cell states and macrophage reprogramming (AACR 2026) - "Cross-model validation identified state-specific candidate drugs, including Leuprolide, Vinblastine, and Mercaptopurine for GLS; Vindesine, Gossypol, and Binimetinib for MOS; and AT9283, Crizotinib, and Afatinib for PLS. Predicted MR-inversion scores correlated with experimental dose-response profiles in cell lines selected via OncoMatch.Together, these results establish a mechanistic link between tumor-intrinsic transcriptional states and macrophage immunosuppression, while identifying mutation-agnostic, state-specific drugs capable of reprogramming both tumor and immune compartments. This work provides a generalizable framework for network-based drug repurposing to overcome transcriptional plasticity and immune resistance in PDAC."

Oncology • Pancreatic Ductal Adenocarcinoma • APOE

Updated overall survival analysis from the phase II PHAROS study of encorafenib plus binimetinib in patients with BRAF V600E-mutant metastatic NSCLC (mNSCLC) (ESMO 2025) - P2 | "Conclusions In this analysis after a median of approximately 4 years of follow-up, enco+bini showed prolonged mOS of approximately 4 years in treatment-naïve pts, which is the longest mOS reported to date with targeted therapies in this patient population from pivotal trials. Long-term safety was consistent with prior analyses, with no new safety signals observed."

Clinical • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF

Real-world outcomes of encorafenib, cetuximab ± binimetinib for BRAF‑mutated metastatic colorectal cancer: The BEETS (JACCRO CC‑18) study. (PubMed, Oncologist) - P=N/A | "In real-world clinical practice, triplet and doublet therapies showed comparable survival outcomes, consistent with the BEACON trial. Triplet therapy may provide potential clinical benefit in patients with poor PFs."

Journal • Real-world evidence • Colorectal Cancer • Oncology • Solid Tumor • BRAF • CRP

Population pharmacokinetics of encorafenib and binimetinib in real-world patients with BRAFV600E/K-mutant metastatic melanoma. (PubMed, Cancer Chemother Pharmacol) - No abstract available

Journal • PK/PD data • Real-world evidence • Melanoma • Oncology • Solid Tumor

Proteomic analysis of BRAF-V600E mutant metastatic colorectal cancer FFPE tissues reveals potential involvement of WEE1 expression in therapeutic resistance (AACR 2026) - "Although targeted therapies such as encorafenib plus cetuximab with or without binimetinib (BEACON regimen) have been developed for this subtype, clinical outcomes remain poor, and overcoming therapeutic resistance represents a critical unmet need. Our proteomic analysis identified WEE1 expression as a potential biomarker associated with poor clinical outcomes in patients with BRAF-V600E mutant mCRC treated with the BEACON regimen. These findings suggest a context-dependent resistance mechanism as a promising therapeutic target warranting further investigation in preclinical and clinical settings."

Metastases • Omic analysis • Colorectal Cancer • Oncology • Solid Tumor • BRAF • WEE1

Triple-targeted therapy with encorafenib, binimetinib and osimertinib in BRAF- and EGFR-co-mutated non-small cell lung cancer: A single-center experience (ELCC 2026) - "While case series reported activity with dabrafenib, trametinib, and osimertinib, there are no published data on the combination of encorafenib, binimetinib, and osimertinib (E+B+O) in this population. E+B+O may be considered in select patients following informed discussion, with close response assessment and monitoring for GI toxicity. Larger prospective studies are needed to validate these findings and optimize patient selection."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • EGFR

STARBOARD: A Clinical Trial of Three Study Medicines (Encorafenib, Binimetinib, and Pembrolizumab) in Patients With Advanced or Metastatic Melanoma (clinicaltrials.gov) - P3 | N=257 | Active, not recruiting | Sponsor: Pfizer | Trial completion date: Mar 2026 ➔ Aug 2026

Trial completion date • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF

PORTSIDE: A Study Comparing 3 Study Medicines (Encorafenib, Binimetinib, Pembrolizumab) to 2 Study Medicines (Ipilimumab and Nivolumab) in Patients With Advanced Melanoma (clinicaltrials.gov) - P2 | N=38 | Terminated | Sponsor: Pfizer | Active, not recruiting ➔ Terminated; Study terminated due to inability to recruit the target number of patients. There were no safety and/or efficacy concerns involved in the decision to stop enrollment.

IO biomarker • Trial termination • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF

Challenges and Outcomes of Immunotherapy in a Solid Organ Transplant Recipient with Metastatic Melanoma (AAD 2026) - "After multidisciplinary discussion, pembrolizumab, an ICI was initiated...Binimetinib, a targeted therapy was initiated due to the presence of an NRAS mutation, but this provided minimal disease control...ICIs remain vital to melanoma treatment, but their use in SOTRs requires extreme caution. Prospective trials and/or multicenter registries are deciding the best route of treatment for these patients is needed to guide management as current alternatives provide limited efficacy."

Clinical • IO biomarker • Metastases • Melanoma • Pneumonia • Solid Organ Transplantation • Solid Tumor • Transplant Rejection • Transplantation • NRAS

A randomized phase 2 trial of encorafenib + binimetinib + nivolumab vs ipilimumab + nivolumab in BRAFV600-mutant melanoma brain metastases: SWOG S2000 (NCT04511013). (ASCO 2025) - P2 | "Steroids up to 8 mg of dexamethasone/day (or equivalent), leptomeningeal spread, and prior local therapy (radiation or surgery) for MBM were permitted, if there was at least one measurable, progressing MBM ≥ 0.5 cm. S2000 is the first randomized trial in patients with symptomatic melanoma brain metastases. A first-line triplet regimen of enco/bini/nivo demonstrated a statistically significant improvement in PFS as compared to ipi/nivo, with a HR of 0.51. Both regimens also had toxicity rates consistent with their known profiles."

Clinical • IO biomarker • Late-breaking abstract • P2 data • Melanoma • Oncology • Solid Tumor

Cotargeting B-Raf and ACLY in Ras mutant cells leads to synergistic loss of cell viability and apoptosis (AACR 2026) - "B-Raf inhibitors Vemurafenib, Dabrafenib and Encorafenib are used clinically in combination with MEK inhibitors Trametinib, Cobimetinib and Binimetinib. All four Ras mutant cell lines showed increased expression of cleaved PARP and the activation of the ER stress pathway regulator ATF4. Finally, the apoptosis stimulated by the combination was shown to be dependent on Caspase-3 activity using Annexin V analysis of HCT116 cells treated with Vemurafenib plus NDI-091143."

Breast Cancer • Colon Cancer • Colorectal Cancer • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • ACLY • ANXA5 • ATF4 • BRAF • CASP3 • RAS

Severe Ileocolitis Associated with Encorafenib/Binimetinib Therapy (USCAP 2026) - "Multifocal ileal and colonic ulcerations with active ileitis/colitis pattern of injury can occur in patients treated with encorafenib/binimetinib. Although most patients had prior ICI treatment, crypt apoptosis and chronic injury were rare, suggesting the findings are specific to this therapy. Despite a low incidence, severe ileocolitis can lead to significant clinical consequences, highlighting the need for recognizing these histopathologic features for timely intervention and management."

IO biomarker • Crohn's disease • Cytomegalovirus Infection • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammatory Bowel Disease • Melanoma • Solid Tumor • BRAF

Patient-derived extracellular matrix scaffolds enable physiologically relevant ex vivo models of vulvar cancer (ESGO 2026) - "Proteomic analysis further revealed increased expression of laminins and matrix-remodelling enzymes in dhECM cultures. Treatment with gefitinib, afatinib, or binimetinib significantly reduced cancer cell invasion and viability in dhECM organotypics.Conclusion Decellularised human ECM hydrogels provide physiologically relevant, tissue-specific scaffolds for ex vivo modelling of vulvar cancer and enable effective preclinical evaluation of targeted therapies."

Preclinical • Gynecologic Cancers • Oncology • Solid Tumor • Squamous Cell Carcinoma • Vulvar Cancer • COL1A1 • COL1A2 • COL2A1 • COL3A1

Comparative Efficacy and Safety of Encorafenib and Binimetinib in First-Line Versus Post-Immunotherapy for BRAFV600-Mutant Metastatic Melanoma: A Systematic Review and Meta-Analysis (EADO 2026) - No abstract available

IO biomarker • Metastases • Retrospective data • Review • Melanoma • Solid Tumor

Population Pharmacokinetic Modeling of Encorafenib in Healthy Participants and Patients with BRAF V600-Mutant Solid Tumors: A Semi-mechanistic Autoinduction Model. (PubMed, Clin Pharmacokinet) - "This model successfully described the PK of encorafenib over time and across tumor types. No dose modifications are suggested on the basis of intrinsic or extrinsic factors evaluated."

Journal • PK/PD data • Colorectal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF

Pathway -targeted combination screening in 3D -spheroids reveals synergistic interactions with everolimus in pancreatic neuroendocrine tumors (ENETS 2026) - " The AKT inhibitor Tuvusertib showed the strongest mo - notherapy effect, although its synergy combined with everolimus was limited. Cytostatic synergy with everolimus was observed with JAK/STAT pathway inhibitors (Conteltinib, Pacritinib) in BON spheroids and with ERK1/2 and PI3K α inhibitors (ASTX029, Gil - melisib) in BON-R spheroids...Cytoto - xic synergy with everolimus was mainly associated with inhibition of the MAPK/ERK pathway, involving ERK inhibitors (Tizaterkib, Ulexertinib) in BON-R spheroids and MEK inhibitors (Binimetinib, Cobimetinib, Trametinib) in both models. High-content 3D spheroid screening integrating NOGR-based growth metrics identified multiple synergistic inter - actions between everolimus and inhibitors targeting interconnec - ted signaling cascades. These findings highlight the potential of rational pathway-targeted combinations to overcome resistance and enhance therapeutic efficacy in pNET, warranting further preclinical investigation to..."

Gastrointestinal Neuroendocrine Tumor • Neuroendocrine Tumor • Oncology • Solid Tumor • PIK3CA

EBIN: Immunotherapy With Ipilimumab and Nivolumab Preceded or Not by a Targeted Therapy With Encorafenib and Binimetinib (clinicaltrials.gov) - P2 | N=271 | Active, not recruiting | Sponsor: European Organisation for Research and Treatment of Cancer - EORTC | Recruiting ➔ Active, not recruiting | Trial primary completion date: Apr 2022 ➔ Nov 2023

Enrollment closed • IO biomarker • Trial primary completion date • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • BRAF

EBIN: Immunotherapy With Ipilimumab and Nivolumab Preceded or Not by a Targeted Therapy With Encorafenib and Binimetinib (clinicaltrials.gov) - P2 | N=270 | Not yet recruiting | Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

IO biomarker • New P2 trial • Melanoma • Mucosal Melanoma • BRAF

EBIN: Immunotherapy With Ipilimumab and Nivolumab Preceded or Not by a Targeted Therapy With Encorafenib and Binimetinib (clinicaltrials.gov) - P2 | N=270 | Not yet recruiting | Sponsor: European Organisation for Research and Treatment of Cancer - EORTC | Initiation date: Feb 2018 ➔ Jul 2018

IO biomarker • Trial initiation date • Melanoma • Mucosal Melanoma • BRAF

Targeting BRAF Fusions with Pan-RAF Inhibitors Highlights Fusion Type–Associated Heterogeneity in Drug Responses and the Need for Combination Therapy with MEK/ERK Inhibitors (IASLC-TTLC 2026) - P1 | "These cell lines were also resistant to the pan-RAS inhibitor RMC-6236 and showed differential sensitivity to pan-RAF inhibitors, with BRAF ex8/9 fusions being the most responsive compared to ex10/11: specifically, average IC50 values for growth inhibition by exarafenib were AGK::BRAFex8: 66nM; AGAP3::BRAFex9: 60nM; TRIM24::BRAFex10: 321nM; SND1::BRAFex11: 1921nM. Similar patterns of sensitivity were observed with other pan-RAF inhibitors (LY3009120, belvarefinib, encorafenib). All CRISPR lines were exquisitely sensitive to MEK1/2 (binimetinib, cobimetinib) and ERK1/2 (ulixertinib) inhibitors, compared to isogenic control cells...We also found that the combination of exarafenib and osimertinib is effective in vivo for EGFR-mutated NSCLC with acquired BRAF fusion. Exarafenib is currently in clinical trials for BRAF- and NRAS-mutant solid tumors (NCT04913285)."

Combination therapy • Heterogeneity • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • AGK • BRAF • EML4 • KIAA1549 • MAP2K1 • NRAS • TRIM24

SAFIR ABC10: Targeted maintenance therapy versus first-line standard of care in advanced biliary cancer. (BWG 2026) - "Introduction: The first-line standard of care (1L-SoC) for advanced biliary tract cancers (ABC), a heterogeneous group of malignancies of the bile ducts and gallbladder, is cisplatin and gemcitabine combined with anti-PD-(L)1...They were randomized to SoC (18 pts, 33%), Futibatinib (13 pts, 24%), Ivosidenib (13 pts, 24%), Zanidatamab (5 pts, 9%), Neratinib-Trastuzumab (1 pt, 2%), Binimetinib-Encorafenib (4 pts, 8%)... SAFIR ABC10 is recruiting at a high pace, with > 50% of the target sample screened, and 34.5% (55/159 pts) randomized. Targetable alterations were found in 104 pts (29%) of patients (including 1% MSI-High pts), of which 55 are randomized. Belgium centres are currently open(ing)."

Clinical • Metastases • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Oncology • Solid Tumor • BRAF • FGFR2 • HER-2 • IDH1

EBIN: Immunotherapy With Ipilimumab and Nivolumab Preceded or Not by a Targeted Therapy With Encorafenib and Binimetinib (clinicaltrials.gov) - P2 | N=270 | Recruiting | Sponsor: European Organisation for Research and Treatment of Cancer - EORTC | Not yet recruiting ➔ Recruiting | Initiation date: Aug 2018 ➔ Oct 2018

Enrollment open • IO biomarker • Trial initiation date • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • BRAF