The greatest benefits of encorafenib plus binimetinib were observed in patients with evidence of high TMB and/or tumor immune infiltration, suggesting potential immune contributions to efficacy, which were not observed with vemurafenib. BRAF V600 detectability in ctDNA appears to have utility as a marker of prognosis and response in this population.

4 days ago

Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • IFNG (Interferon, gamma)

PD-L1 expression • BRAF V600E • TMB-H • BRAF V600 • BRAF V600K

Zelboraf (vemurafenib) • Mektovi (binimetinib) • Braftovi (encorafenib)

GEMOX Combined With Donafenib and Tislelizumab in Advanced Biliary Tract Carcinoma (clinicaltrials.gov)

P2, N=93, Recruiting, Fudan University | Trial primary completion date: Sep 2026 --> Dec 2026

5 days ago

Trial primary completion date

gemcitabine • Tevimbra (tislelizumab-jsgr) • oxaliplatin • Zepsun (donafenib)

RAMP 203: Phase 1/2 Study of Avutometinib (VS-6766) + Sotorasib With or Without Defactinib in KRAS G12C NSCLC Patients (clinicaltrials.gov)

P1/2, N=153, Active, not recruiting, Verastem, Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2025 --> Jun 2026

7 days ago

Enrollment closed • Trial primary completion date

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12

Lumakras (sotorasib) • Avmapki (avutometinib) • Fakzynja (defactinib)

13d

OCEANII: Phase II Study Investigating the Combination of Encorafenib and Binimetinib in BRAF V600E Mutated Chinese Patients With Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov)

P2, N=63, Active, not recruiting, Pierre Fabre Medicament | Trial completion date: Sep 2026 --> Dec 2026

13 days ago

Trial completion date

BRAF V600E • BRAF V600

Mektovi (binimetinib) • Braftovi (encorafenib)

13d

CHANCE 2203: HAIC Combined With Donafenib and Sintilimab for Unresectable ICC (clinicaltrials.gov)

P2, N=25, Completed, Zhongda Hospital | Recruiting --> Completed | Trial completion date: Jul 2023 --> Oct 2025 | Trial primary completion date: Jun 2023 --> Oct 2025

13 days ago

Trial completion • Trial completion date • Trial primary completion date

Tyvyt (sintilimab) • oxaliplatin • Zepsun (donafenib)

13d

Phase Ib Study of Avutometinib, Defactinib, and Everolimus in RAS Pathway Mutant Endometrial Cancer (clinicaltrials.gov)

P1, N=31, Not yet recruiting, M.D. Anderson Cancer Center

13 days ago

New P1 trial

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • MAP2K2 (Mitogen-activated protein kinase kinase 2)

KRAS mutation • BRAF mutation • NRAS mutation • RAS mutation • HRAS mutation

everolimus • Avmapki (avutometinib) • Fakzynja (defactinib)

15d

BRICKET: Phase II Study of ctDNA-guided Encorafenib Plus Cetuximab Retreatment in Patients BRAF V600E Mutated mCRC (clinicaltrials.gov)

P2, N=16, Active, not recruiting, Gruppo Oncologico del Nord-Ovest | Recruiting --> Active, not recruiting

15 days ago

Enrollment closed • Circulating tumor DNA

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • MAP2K1 (Mitogen-activated protein kinase kinase 1)

BRAF V600E • MSI-H/dMMR • BRAF V600 • KRAS wild-type • NRAS wild-type

Guardant360® CDx

Erbitux (cetuximab) • Braftovi (encorafenib)

15d

Stereotactic Body Radiotherapy Plus FAK and RAF/MEK Inhibition in Advanced Pancreatic Adenocarcinoma (clinicaltrials.gov)

P2, N=36, Not yet recruiting, Washington University School of Medicine

15 days ago

New P2 trial

Avmapki (avutometinib) • Fakzynja (defactinib)

17d

Binimetinib and encorafenib for the treatment of advanced solid tumors with non-V600E BRAF mutations: results from the Phase II BEAVER trial. (PubMed, Nat Commun)

CDK4/6 and SHP2 emerge as mediators of intrinsic resistance to BRAF/MEK inhibition in Class 2 & 3 BRAF mutant tumors. Therapeutic strategies combining CDK4/6 or SHP2 inhibitors with BRAF/MEK inhibitors in preclinical models show greater efficacy than BRAF/MEK inhibitors alone in these cancers.

17 days ago

P2 data • Journal

BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1)

BRAF V600E • NRAS mutation

Mektovi (binimetinib) • Braftovi (encorafenib)

25d

LncRNA ZFAS1 in hepatocellular carcinoma: A systematic review of molecular mechanisms and clinical translation. (PubMed, Noncoding RNA Res)

Clinically, plasma ZFAS1 demonstrates enhanced diagnostic utility when combined with alpha-fetoprotein (AUC = 0.891), while therapeutic targeting of ZFAS1-mediated PI3K-AKT and PERK/ATF4 pathways shows promise in overcoming sorafenib/donafenib resistance. Current translational challenges include ZFAS1 isoform heterogeneity, suboptimal liquid biopsy sensitivity, and dynamic TME interactions. Future directions should employ multi-omics integration (spatial transcriptomics/single-cell sequencing) coupled with AI-driven network modeling to systematically decode ZFAS1's regulatory architecture, ultimately enabling precision theranostic strategies for HCC management.

25 days ago

Review • Journal

MET (MET proto-oncogene, receptor tyrosine kinase) • AFP (Alpha-fetoprotein) • ATF4 (Activating Transcription Factor 4) • ZEB1 (Zinc Finger E-box Binding Homeobox 1) • AIFM2 (Apoptosis Inducing Factor Mitochondria Associated 2) • MIR150 (MicroRNA 150) • MIR193A (MicroRNA 193a) • MMP14 (Matrix Metallopeptidase 14) • ZFAS1 (ZNFX1 Antisense RNA 1)

sorafenib • Zepsun (donafenib)

30d

Neo-TACE: Neoadjuvant HAIC of TACE Plus Donafenib in BCLC B Stage HCC: a Multi-center Randomized Controlled Trial. (clinicaltrials.gov)

P2/3, N=18, Terminated, Peking University | N=156 --> 18 | Trial completion date: Dec 2027 --> Oct 2025 | Recruiting --> Terminated | Trial primary completion date: Dec 2026 --> Oct 2025; Difficult to enroll participants

30 days ago

Enrollment change • Trial completion date • Trial termination • Trial primary completion date

5-fluorouracil • oxaliplatin • leucovorin calcium • Zepsun (donafenib)