Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Medison, Nerviano Medical Sciences - LARVOL DELTA

Pharmacokinetics of Binimetinib in Participants with Hepatic Impairment. (PubMed, Clin Pharmacokinet) - P1 | "Based on these findings on total and unbound exposures, dose reductions are recommended for binimetinib in cancer patients with moderate and severe HI."

Journal • PK/PD data • Hepatology • Oncology

BRAF inhibitors in Melanoma: Structural Insights, Therapeutic Resistance, and Biological Evaluation of Quinazoline Derivatives. (PubMed, Eur J Med Chem) - "Recent studies found that FDA-approved BRAF inhibitors such as Dabrafenib, Vemurafenib, and Encorafenib acquired resistance towards the therapy (It could be either intrinsic resistance or acquired resistance), furthermore, these candidates are involved in RAS-dependent paradoxical activation of the MAPK pathway. So, in this review, we have analysed the BRAF structure, its activation process, downstream signalling pathway, mutation, the drugs capable of inhibiting the mutant BRAFV600E activity and the therapeutic adherence linked to the FDA-approved medications. We have particularly focused on the recent development of various quinazoline-based compounds with strong evidence covering structure-activity relationship, molecular docking and the key amino acid interactions that guide the researchers to design and synthesize novel Quinazoline analogues as potent BRAF inhibitors."

Journal • Review • Fibrosarcoma • Melanoma • Oncology • Sarcoma • Solid Tumor

Testing the Addition of Anti-cancer Drug, ZEN003694, to the Usual Chemotherapy Treatment, Cetuximab Plus Encorafenib, for Colorectal Cancer (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2025 ➔ Jan 2027 | Trial primary completion date: Jun 2025 ➔ Jan 2027

Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor • BRAF

Real-world use of encorafenib + cetuximab (EC) in patients with BRAFV600E-mutant metastatic colorectal cancer (mCRC): a pooled analysis of European observational studies (ESMO-GI 2025) - No abstract available

Metastases • Observational data • Real-world • Real-world evidence • Retrospective data • Colorectal Cancer • Oncology • Solid Tumor

BREAKWATER: Post-hoc subgroup efficacy analyses by chemotherapy _ bevacizumab regimens vs encorafenib plus cetuximab + mFOLFOX6 (ESMO-GI 2025) - No abstract available

Clinical • Retrospective data • Gastrointestinal Cancer

Switch from cetuximab (CET) to panitumumab (PANI) during encorafenib (ENCO)-based therapy in BRAF V600E mutated metastatic colorectal cancer (mCRC): an international multicenter analysis from the AGEO group. (ESMO-GI 2025) - No abstract available

Clinical • Metastases • Colorectal Cancer • Oncology • Solid Tumor • BRAF

A Canadian Real-World Evidence Study of Panitumumab with Encorafenib in BRAF V600E Mutated Metastatic Colorectal Cancer (mCRC) (ESMO-GI 2025) - No abstract available

Clinical • HEOR • Metastases • Real-world • Real-world evidence • Colorectal Cancer • Oncology • Solid Tumor • BRAF

Encorafenib plus cetuximab in patients with metastatic, BRAF V600E-mutated, colorectal carcinoma - effectiveness and treatment reality of the European multi-centric, multi-national, non-interventional study - BERING CRC (ESMO-GI 2025) - No abstract available

Clinical • Metastases • Observational data • Colorectal Cancer • Oncology • Solid Tumor • BRAF

UK-EnBiRiM: UK ENcorafenib and BInimetinib Real-world Study in Melanoma (clinicaltrials.gov) - P=N/A | N=50 | Not yet recruiting | Sponsor: Vitaccess Ltd

New trial • Real-world evidence • Melanoma • Oncology • Solid Tumor • BRAF

Cardiovascular Safety Profile of BRAF and MEK Inhibitors in Melanoma: FAERS Data Through a Retrospective Disproportionality Analysis (2014-2023). (PubMed, Cancers (Basel)) - " Descriptive and disproportionality analyses were conducted on reports listing dabrafenib (D), vemurafenib (V), encorafenib (E), trametinib (T), cobimetinib (C), or binimetinib (B) as suspects in monotherapy or combination therapy (D + T, V + C, E + B), with melanoma as the indication and at least one cAE. Among embolic and thrombotic events, clinically significant SDRs were observed for disseminated intravascular coagulation with D + T (38; 10.22, 7.42-14.06) and pulmonary embolism with V + C (22; 2.79, 1.83-4.24). Our findings underscore the need for comprehensive CV monitoring in patients receiving BRAF/MEKi therapy to prevent or detect cAEs early and reduce treatment-related risks, particularly in high-risk populations."

Journal • Retrospective data • Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Heart Failure • Melanoma • Oncology • Pulmonary Embolism • Respiratory Diseases • Solid Tumor

POLARIS: encorafenib plus binimetinib for people with BRAF V600-mutant melanoma with brain metastasis. (PubMed, Future Oncol) - "In the safety lead-in, many patients were unable to tolerate the high dose of encorafenib plus binimetinib. Despite recruitment challenges in POLARIS, in the 13 enrolled patients with unresectable metastatic BRAF V600-mutant melanoma with brain metastases, treatment with encorafenib plus binimetinib demonstrated intracranial activity, with a brain metastasis response rate of over 60%."

Journal • Melanoma • Oncology • Solid Tumor • BRAF

Strong Hsp90α/β Protein Expression in Advanced Primary CRC Indicates Short Survival and Predicts Response to the Hsp90α/β-Specific Inhibitor Pimitespib. (PubMed, Cells) - "Pimitespib (Pim, TAS-116), a Hsp90α/β-specific inhibitor, was tested in pCRC cell lines and patient-derived cancer spheroids (PDCS) and referenced to the pan-Hsp90 inhibitor ganetespib (Gan, STA-9090) and standard-of-care therapies...Pim efficacy was increased in combination with 5-FU, 5-FU + oxaliplatin, and 5-FU + irinotecan (all p 40% pCRCs. Protein profiling combined with functional drug testing stratifies Hsp90α/β > 40% pCRC patients diagnosed with UICC IIb-IV for effective Pim-based therapy."

Journal • Colorectal Cancer • Oncology • Solid Tumor • BRAF • CDC37 • HER-2 • HSP90AA1

Drug-Related Visual Blurring: Findings from the U.S. Food and Drug Administration Adverse Event Reporting System Database. (PubMed, Eur J Pharmacol) - "Preventing drug-related vision issues is vital. Early risk assessment and intervention with personalized medication can reduce side effects, ensure safety, and improve quality of life."

Adverse events • Journal • Oncology • Ophthalmology • Retinal Disorders

Testing Treatment With Encorafenib and Binimetinib Before Surgery for Melanoma With Lymph Node Involvement (clinicaltrials.gov) - P2 | N=3 | Terminated | Sponsor: ECOG-ACRIN Cancer Research Group | Active, not recruiting ➔ Terminated | Trial primary completion date: Feb 2025 ➔ Jun 2024; Slow accrual

Trial primary completion date • Trial termination • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF • CD4

ENCEFALO: Encorafenib and biNimetinib Followed by CEmiplimab and FiAnLimab in Patients With BRAF Mutant melanOma and Symptomatic Brain Metastases (clinicaltrials.gov) - P2 | N=33 | Recruiting | Sponsor: Grupo Español Multidisciplinar de Melanoma | Not yet recruiting ➔ Recruiting

Enrollment open • Melanoma • Oncology • Solid Tumor

Updated Efficacy and Safety From the Phase 2 PHAROS Study of Encorafenib Plus Binimetinib in Patients With BRAF V600E-Mutant Metastatic NSCLC‒A Brief Report. (PubMed, J Thorac Oncol) - "With longer follow-up, encorafenib plus binimetinib showed durable and clinically meaningful antitumor activity, especially in treatment-naïve patients, with a manageable safety profile in patients with BRAF V600E-mutant mNSCLC."

Journal • P2 data • Fatigue • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF

Biomarker testing in metastatic colorectal cancer (mCRC): 2015-2024 trends in the United States (US) community oncology setting. (ASCO 2025) - "In 2020, following the approval of tucatinib, HER2 testing rates increased from 32%-66% prior to 2019 to 89%-93% after 2020. BRAF testing rates also increased to 90%-96% after 2017, following the approval of encorafenib plus cetuximab combination therapy for BRAF-mutated mCRC in 2018. NTRK testing rates (21%-42%) showed improvement over the study period, with the highest proportion of patients tested in 2024 corresponding to the accelerated approval of repotrectinib for in the same year. Similarly, RET testing (25%-89%) peaked in 2023 following breakthrough therapy designation for selpercatinib in late 2022... As new targeted therapies have emerged in recent years, biomarker testing rates for mCRC have rapidly increased in the community oncology setting. NTRK or RET rearrangements are infrequent in advanced CRC, with lower testing rates for these genes within the study period. However, as this study leveraged structured data only, actual rates of testing may be even..."

Biomarker • Metastases • Colorectal Cancer • Oncology • Solid Tumor • BRAF • HER-2 • KRAS • NRAS • NTRK

Structural Insights into allosteric inhibition of HRI kinase by heme binding via HDX-MS. (PubMed, Biochem J) - "We examined several competitive ATP-mimetic inhibitors-Dabrafenib, Encorafenib, and GCN2iB-and compared them to the heme-mimetic allosteric inhibitor, hemin. Our analysis revealed that hemin inhibition induces large-scale structural rearrangements in HRI, which are not observed with ATP-mimetic inhibitors. Our results suggest that HRI may be inhibited using two distinctly different modalities which may guide future drug development."

Journal • CNS Disorders • Oncology

A phase II study of encorafenib and cetuximab (EC) beyond progression in combination with FOLFIRI in BRAF V600E-mutated metastatic colorectal cancer (mCRC). (ASCO 2025) - P2 | "If at least 7 pts will be alive and not progressing at 6 months, the treatment will be considered sufficiently active to warrant further investigation. The study is currently enrolling at multiple sites in Italy."

Combination therapy • Metastases • P2 data • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor • BRAF

Impact of a molecular tumor board on treatment decisions for advanced solid tumors: Experience from a Portuguese cancer center. (ASCO 2025) - "Clinical benefit was observed in 10 (6%) patients, with 1 complete response (CR) (porocarcinoma TMB-high under pembrolizumab), 3 partial responses (PR) (myofibroblastic tumor, mROS1, under lorlatinib; neuroblastoma, mALK, under lorlatinib; melanoma, mBRAF V600E not detected by PCR, under encorafenib/binimetibib), and 6 stable diseases (SD). These findings indicate that MTB-guided therapy may enhance clinical outcomes with manageable toxicity in a subset of patients with advanced, refractory malignancies. The study highlights the necessity of further investigation into resistance mechanisms and the incorporation of molecularly guided decisions in earlier treatment lines."

Metastases • Lung Cancer • Melanoma • Neuroblastoma • Oncology • Solid Tumor • BRAF • KRAS • NRAS • PIK3CA • TMB • TP53

Survival analysis based on markers of progression in melanoma: A single-center comparison of survival in patients with high vs low biomarkers. (ASCO 2025) - "Patients included in the analysis were treated systemically with pembrolizumab, encorafenib/binimetinib, nivolumab, or ipilimumab/nivolumab. Our findings show that patients with higher levels of ctDNA and LDH have significantly shorter survival compared to those with low levels of these biomarkers. While NLR did not show a significant survival difference, the study suggests that higher ctDNA and LDH could be important markers for identifying patients at greater risk of poor outcomes. These results underscore the potential value of monitoring these biomarkers to assess disease progression and survival in melanoma patients."

Biomarker • Clinical • Melanoma • Oncology • Solid Tumor

Triplet therapy with BRAF inhibitor, anti-EGFR agent, and MEK inhibitor in V600E BRAF–mutant colorectal cancer: A meta-analysis. (ASCO 2025) - "Funded by No funding sources reported Background: The BRAF inhibitor (BRAFi) encorafenib is currently approved in combination with the anti-EGFR agent cetuximab for patients with previously treated V600E BRAF mutant CRC (mCRC). Our analysis revealed a significant ORR benefit for TT compared to any DT regimen. Among the DT regimens, BRAFi + anti-EGFR showed a higher DCR than BRAFi + MEKi, with comparable ORR. While our findings are limited by the heterogeneity of the included studies, most of which were single-arm trials, they highlight the potential of TT as promising approach that warrants further investigation in future studies, ideally through randomized controlled trials."

Retrospective data • Colorectal Cancer • Oncology • Solid Tumor

Exploring the efficacy and mechanism of action of combined pan-Raf and MEK inhibition in halting the growth of non-V600 BRAF mutated tumors. (ASCO 2025) - P2 | "Encorafenib (Enco; BRAF monomer inhibitor) + Binimetinib (Bini; MEK inhibitor) elicit responses in <15% of patients with non-V600E BRAF mutations (NCT03839342). We hypothesized that Belvarafenib (Belva), a novel pan-RAF dimer inhibitor, is more potent than Enco in inhibiting the growth of Class 2 & 3 non-V600 BRAF mutated tumors... These results from 10 preclinical models, tested so far, put forward combined Pan-Raf and MEK inhibition as a potential effective treatment choice for patients with non-V600 BRAF mutated tumors to be investigated in clinical trials. In parallel, they unravel novel insights into the mechanism of action of this therapeutic approach and in return the druggable vulnerabilities of the non-V600 BRAF mutated tumors, a notion we are further investigating in the outlined models."

Clinical • Colorectal Cancer • Melanoma • Oncology • Solid Tumor • BRAF

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

Long-term off-label MAPK inhibitor therapy in children with severe/refractory Langerhans cell histiocytosis: An international observational study of 277 cases. (ASCO 2025) - "252 patients had received one or several lines of chemotherapies prior to MAPKi: VBL/steroids (n = 243) then 2CdA/AraC (n = 48), 2CdA alone (n = 52), clofarabine (n = 5), VCR/AraC (n = 70) before being considered refractory...Vemurafenib (n = 177), Dabrafenib (n = 105), Encorafenib (n = 3), Cobimetinib (n = 41), Tramatinib (n = 41), and Binimetinib (n = 1) were prescribed mainly in monotherapy, sometimes (n = 44) with various chemotherapies or HSCT (n = 5)... MAPKi appeared quick, safe and effective in children with refractory LCH while the response to Lung, SC, DI and ND was limited or delayed. Further studies are needed to find effective maintenance therapy. ND should be monitored in the follow up of patients treated by MAPKi."

Clinical • Observational data • Bone Marrow Transplantation • Cardiomyopathy • Cardiovascular • CNS Disorders • Dermatology • Genetic Disorders • Hepatology • Langerhans Cell Histiocytosis • Metabolic Disorders • Ocular Inflammation • Oncology • Ophthalmology • Retinal Disorders • Solid Tumor