Zelboraf (vemurafenib) / Daiichi Sankyo, Roche - LARVOL DELTA

Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial) (clinicaltrials.gov) - P2 | N=1376 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: May 2026 ➔ Jan 2027

Biomarker • Trial completion date • Brain Cancer • CNS Tumor • Embryonal Tumor • Ependymoma • Ewing Sarcoma • Germ Cell Tumors • Glioma • Hematological Malignancies • Hepatoblastoma • High Grade Glioma • Langerhans Cell Histiocytosis • Lymphoma • Medulloblastoma • Nephrology • Neuroblastoma • Non-Hodgkin’s Lymphoma • Oncology • Osteosarcoma • Pediatrics • Rhabdoid Tumor • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor • BRAF

Bleeding Complications of BRAF Inhibitors. (PubMed, Clin Oncol (R Coll Radiol)) - "Evidence to guide rechallenge is sparse. Resumption after minor events may be reasonable with dose modification and close monitoring, whereas major or intracranial bleeding generally warrants discontinuation unless a compelling oncologic indication exists and multidisciplinary consensus supports cautious reinitiation after shared-decision making."

Journal • Cerebral Hemorrhage • CNS Disorders • Melanoma • Oncology • Solid Tumor

Overall survival with first-line atezolizumab in combination with vemurafenib and cobimetinib in BRAF mutation-positive advanced melanoma (IMspire150): second interim analysis of a multicentre, randomised, phase 3 study. (PubMed, Lancet Oncol) - P3 | "Additional follow-up of the IMspire150 trial showed that overall survival was not significantly improved with atezolizumab, vemurafenib, and cobimetinib compared with placebo, vemurafenib, and cobimetinib in patients with BRAF mutation-positive advanced melanoma. Results of the final analysis are awaited to establish whether a significant improvement in overall survival can be achieved with long-term treatment with this triplet combination versus vemurafenib plus cobimetinib."

Combination therapy • Journal • P3 data • P3 data: top line • Hepatology • Inflammation • Liver Failure • Melanoma • Oncology • Solid Tumor • BRAF

Combination or sequence of vemurafenib, cobimetinib, and atezolizumab in high-risk, resectable melanoma (NEO-TIM): Primary results. (ASCO 2024) - P2 | "Pts treated with TT upfront had highest response to NAT but the pts who received IO as NAT had a better RFS."

Late-breaking abstract • Melanoma • Oncology • Solid Tumor • BRAF

Atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases (TRICOTEL): a multicentre, open-label, single-arm, phase 2 study. (PubMed, Lancet Oncol) - P2 | "Adding atezolizumab to vemurafenib plus cobimetinib provided promising intracranial activity in patients with BRAF-mutated melanoma with CNS metastases."

IO biomarker • Journal • P2 data • CNS Disorders • Dermatitis • Dermatology • Hematological Disorders • Immunology • Melanoma • Oncology • Solid Tumor • BRAF

Early switch from run-in with targeted to immunotherapy in advanced BRAFV600-positive melanoma: final results of the randomised phase II ImmunoCobiVem trial. (PubMed, ESMO Open) - "Early switch to ICIs after TT run-in (arm B) led to an improved, although not statistically significant, 4- and 5-year landmark OS compared with arm A. No subgroups were identified for which a TT run-in provided clinical benefit. The number of patients developing brain metastasis and the time to brain metastasis were not improved by an early TT to ICI switch."

Journal • P2 data • Melanoma • Oncology • Solid Tumor • PD-1

Early switch from targeted to immunotherapy in advanced BRAFV600-positive melanoma: Long-term OS and final PFS results of the randomized phase II ImmunoCobiVem trial (ESMO 2024) - P2 | "While first-line ICI is superior to TT in terms of overall survival (OS), it is still uncertain whether a short run-in with TT and switch to ICI before progression may improve benefit. The 1:1 randomised phase 2 ImmunoCobiVem trial compared – after a 3-month run-in phase with vemurafenib (V, 960 mg twice daily) and cobimetinib (C, 60 mg daily d 21-28, Q4W) – in Arm A continuous V+C until progressive disease (PD1) and second-line (2L) atezolizumab (ATEZO, 1200 mg Q3W) versus (Arm B) early switch to ATEZO after the run-in phase and then crossover to V+C at PD1. The early switch to ICI after TT run-in led to an improved landmark OS at 4- and at 5-years compared to Arm A, although not statistically significant. The better early tumor control (PFS1) in Arm A and treatment options outside the trial diluted the overall effect size for early switch to ICI, so that it remained small. No subgroups were identified for which a TT run-in (Arm B) provided clinical benefit."

Clinical • Late-breaking abstract • Metastases • P2 data • Melanoma • Oncology • Skin Cancer • Solid Tumor • PD-1

Atezolizumab (A), cobimetinib (C), and vemurafenib (V) in patients (pts) with BRAFV600 mutation–positive melanoma with central nervous system (CNS) metastases (mets): Primary results from phase 2 Tricotel study. (ASCO 2022) - P2 | "Prespecified subgroup analyses were performed in pts receiving corticosteroids (>2 mg/d dexamethasone) and/or with CNS-related symptoms at baseline vs asymptomatic pts. Addition of A to C + V provides promising intracranial activity in pts with BRAFV600-mutated melanoma with CNS mets, particularly in those receiving corticosteroids and/or in symptomatic pts. The safety profile of A + C + V is consistent with that observed in the IMspire150 study."

Clinical • IO biomarker • P2 data • Immunology • Melanoma • Oncology • Solid Tumor

Overall survival (OS) with first-line atezolizumab (A) or placebo (P) in combination with vemurafenib (V) and cobimetinib (C) in BRAFV600 mutation-positive advanced melanoma: Second interim OS analysis of the phase 3 IMspire150 study. (ASCO 2022) - P3 | "With further follow-up, A + V + C demonstrated a consistent, but not statistically significant, improvement in OS and continued benefit in duration of response versus P + V + C in previously untreated pts with BRAFV600 mutation–positive advanced melanoma."

Clinical • Combination therapy • P3 data • P3 data: top line • Melanoma • Oncology • Solid Tumor

Anti-Programmed Death Ligand 1 Plus Targeted Therapy in Anaplastic Thyroid Carcinoma: A Nonrandomized Clinical Trial. (PubMed, JAMA Oncol) - P2 | "Patients were assigned to targeted therapy based on the driver mutation as follow: BRAF V600E (cohort 1, vemurafenib plus cobimetinib), RAS/NF (cohort 2, cobimetinib), or non-BRAF/RAS/NF (cohort 3, bevacizumab). In this nonrandomized clinical trial, atezolizumab combined with targeted therapy resulted in a longer median OS than historical landmark, achieving the study's primary end point, with cohort 1 achieving the longest OS. ClinicalTrials.gov Identifier: NCT03181100."

Clinical • IO biomarker • Journal • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • BRAF • HRAS • KRAS • NF1 • NRAS

IMPRESS-Norway: A nationwide precision-oncology study for off-label targeted therapies - Results from the first 1,740 patients (ESMO 2025) - P2 | "The most common treatments were trametinib ± dabrafenib (n=72), trastuzumab + pertuzumab (n=51), atezolizumab ± bevacizumab (n=48), alpelisib ± fulvestrant (n=30) and cobimetinib + vemurafenib (n=23). Among patients with CR, PR or SD (80/250), the median duration of treatment was 41 weeks. Conclusions IMPRESS-Norway demonstrates how a publicly funded and equally accessible precision medicine framework can be implemented and provides DCR in 32% of patients."

Clinical • Biliary Cancer • Brain Cancer • Cholangiocarcinoma • Colorectal Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

Neoadjuvant cobimetinib and atezolizumab with or without vemurafenib for high-risk operable Stage III melanoma: the Phase II NeoACTIVATE trial. (PubMed, Nat Commun) - P2 | "No surgical delays nor progression to regional unresectability occurred (secondary outcome). Peripheral blood CD8 + TCM cell expansion associated with favorable pathologic responses (exploratory outcome)."

IO biomarker • Journal • P2 data • Dermatology • Melanoma • Oncology • Solid Tumor • BRAF • CD8

Intermittent BRAF inhibition in advanced BRAF mutated melanoma results of a phase II randomized trial. (PubMed, Nat Commun) - P2 | "Contrary to expectations, the first published phase 2 randomized study comparing continuous versus intermittent schedule of dabrafenib (BRAFi) plus trametinib (MEKi) demonstrated a detrimental effect of the "on-off" schedule. Here we report confirmatory data from the Phase II randomized open-label clinical trial comparing the antitumoral activity of the standard schedule versus an intermittent combination of vemurafenib (BRAFi) plus cobimetinib (MEKi) in advanced BRAF mutant melanoma patients (NCT02583516)...Detection of BRAF mutation in cell free tumor DNA has prognostic value for survival and its dynamics has an excellent correlation with clinical response, but not with progression. NGS analysis demonstrated de novo mutations in resistant cases."

Clinical • Journal • P2 data • Melanoma • Oncology • Solid Tumor

Isolated Cutaneous Adult Langerhans Cell Histiocytosis treated with Vemurafenib: a case presentation (AAD 2026) - No abstract available

Clinical • Langerhans Cell Histiocytosis

Catestatin peptide impedes melanoma progression and drug resistance by reprogramming oncogenic signaling pathways. (PubMed, Res Sq) - "In Vemurafenib-resistant A375 cells, CST increased apoptosis and repressed multiple resistance associated genes. These results highlight CST as a promising therapeutic candidate capable of opposing melanoma progression and overcoming resistance to current targeted treatments."

Journal • Melanoma • Oncology • Solid Tumor

Exploring the role of the key gene TNFAIP3 between periodontitis and influenza A through bioinformatic analysis and molecular docking. (PubMed, PLoS One) - "Ultimately, machine learning algorithms identified TNFAIP3 as a common key gene for PD and IA, and further identified five drugs: Vemurafenib, Metformin, Dexamethasone, Tretinoin and Imatinib with potential for combined treatment of PD and IA. Our study reveals the shared mechanism and immune profile of TNFAIP3 as a key gene in PD and IA, which lays a theoretical foundation for future targeted therapies based on the shared mechanism of the two diseases."

Journal • Dental Disorders • Infectious Disease • Influenza • Periodontitis • Respiratory Diseases • TNFAIP3

Cobimetinib Plus Vemurafenib in Patients With Colorectal Cancer With BRAF Mutations: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study. (PubMed, JCO Precis Oncol) - "The combination of C + V has antitumor activity in heavily pretreated patients with CRC with BRAF mutations."

Journal • Colorectal Cancer • Endocrine Disorders • Fatigue • Gastrointestinal Cancer • Gastrointestinal Disorder • Hematological Disorders • Metabolic Disorders • Oncology • Pulmonary Disease • Renal Disease • Solid Tumor • BRAF • MAP2K1 • NRAS

Long-Term Real-World Outcomes and Safety of Vemurafenib and Vemurafenib + Cobimetinib Therapy in Patients with BRAF-Mutated Melanoma. (PubMed, Target Oncol) - "We confirmed significant improvement in the mOS and mPFS of unresectable and/or metastatic BRAF mutated-melanoma patients treated outside clinical trials with V + C as compared with V, with no major increase in toxicity for the combination."

Journal • Real-world • Real-world evidence • Melanoma • Oncology • Solid Tumor • BRAF

Cobimetinib Plus Vemurafenib in Patients With Solid Tumors With BRAF Mutations: Results From the Targeted Agent and Profiling Utilization Registry Study. (PubMed, JCO Precis Oncol) - "Cobimetinib plus vemurafenib showed antitumor activity in patients with advanced solid tumors with BRAF V600E mutations; additional study is warranted to confirm the antitumor activity in tumors with non-V600E BRAF mutations."

Journal • Oncology • Ovarian Cancer • Renal Disease • Solid Tumor • BRAF

BRAF-MEK Inhibition in Newly Diagnosed Papillary Craniopharyngiomas. (PubMed, N Engl J Med) - P2 | "In this small, single-group study involving patients with papillary craniopharyngiomas, 15 of 16 patients had a partial response or better to the BRAF-MEK inhibitor combination vemurafenib-cobimetinib. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT03224767.)."

Journal • Brain Cancer • CNS Tumor • Diabetes • Endocrine Cancer • Endocrine Disorders • Oncology • Solid Tumor

Cobimetinib plus vemurafenib (C+V) in patients (Pts) with solid tumors with BRAF V600E/d/k/R mutation: Results from the targeted agent and profiling utilization registry (TAPUR) study. (ASCO 2022) - P2 | "C+Vdemonstrated evidence of anti-tumor activity in pts with advanced solid tumors with BRAF V600E and other muts."

Clinical • Breast Cancer • Oncology • Ovarian Cancer • Renal Disease • Solid Tumor • BRAF • MAP2K1 • NRAS

Contribution of MEK Inhibition to BRAF/MEK Inhibitor Combination Treatment of BRAF-Mutant Melanoma: Part 2 of the Randomized, Open-Label, Phase III COLUMBUS Trial. (PubMed, J Clin Oncol) - "COMBO300 improved PFS, ORR, and tolerability compared with ENCO300, confirming the contribution of binimetinib to efficacy and safety."

Journal • P3 data • Melanoma • Oncology • Solid Tumor • BRAF

COLUMBUS 5-Year Update: A Randomized, Open-Label, Phase III Trial of Encorafenib Plus Binimetinib Versus Vemurafenib or Encorafenib in Patients With BRAF V600-Mutant Melanoma. (PubMed, J Clin Oncol) - P3 | "In this 5-year update of part 1 of the COLUMBUS trial, encorafenib plus binimetinib treatment demonstrated continued long-term benefits and a consistent safety profile in patients with BRAF V600-mutant melanoma."

IO biomarker • Journal • P3 data • Melanoma • Oncology • Solid Tumor • BRAF

Pan-Cancer Efficacy of Vemurafenib in BRAFV600-Mutant Non-Melanoma Cancers. (PubMed, Cancer Discov) - "Responses were observed in 13 unique cancer types, including historically treatment-refractory tumors such as cholangiocarcinoma, sarcoma, glioma, neuroendocrine carcinoma, and salivary gland carcinomas. Collectively, these data demonstrate that single-agent BRAF inhibition has broader clinical activity than previously recognized."

Clinical • Journal • Biliary Cancer • Brain Cancer • Cholangiocarcinoma • CNS Disorders • Colorectal Cancer • Gastrointestinal Cancer • Glioma • Neuroendocrine Tumor • Salivary Gland Cancer • Sarcoma • Solid Tumor • BRAF

Sox9-dependent acquisition of a drug resistant "memory state" induces reciprocal expression of Sox6 and Sox7 in BRAF melanoma. (PubMed, Biochim Biophys Acta Mol Cell Res) - "Using a panel of BRAFV600E positive YUMM lines, we find that, following chronic vemurafenib treatment, SOX10 is lost whereas SOX9 is induced...Overall, our data show that the loss of SOX10 and SOX9 induction are critical to program drug resistance. Furthermore, we show that the YUMM cell lines represent a good murine model to investigate transitions to an acquired drug resistant state."

Journal • Melanoma • Oncology • Solid Tumor • BRAF • SOX10 • SOX9