Cotellic (cobimetinib) / Exelixis, Roche - LARVOL DELTA

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

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 of vemurafenib with cobimetinib in BRAF V600E/K mutated melanoma patients to normalize LDH and optimize immunotherapy with nivolumab and ipilimumab (COWBOY): A randomized, open-label phase 2 clinical trial. (ASCO 2026) - P2 | "BRAF/MEKi induction prior to dual ICI did not improve response rates to ICI and was associated with worse PFS and OS in pts with BRAFV600E/K mutated melanoma and elevated LDH compared to upfront dual ICI."

Clinical • IO biomarker • P2 data • Melanoma • Solid Tumor • BRAF

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

Feasibility and outcome of genomics-guided treatment selection in advanced cancer - the MEGALiT explorative clinical trial. (PubMed, Acta Oncol) - "Genomics-guided treatment selection in advanced cancer is feasible and safe. However, evidence of patient benefit warrants further investigation."

Biomarker • Journal • Oncology • Ovarian Cancer • Solid Tumor

COTESARC: A multicentre, open-label, phase I-II evaluating the combination of MEK and PDL-1 inhibitors in patients with advanced soft tissue sarcoma (STS) (ESMO 2025) - P1/2 | "Methods Cobimetinib (60 mg orally, once daily for days 1 – 21 over 28 day-cycle) plus atezolizumab (840 mg, IV, every 2 weeks) were evaluated in patients (pt) with complex genomic (CG) STS, single genomic (SG) STS, malignant peripheral nerve sheath tumors (MPNST), and rhabdomyosarcoma (RMS). Some pts with different histotypes strongly benefited from the combination. Translational data will be presented including spatial transcriptomics, RNAseq and multi-immunofluorescence on tumor samples."

Clinical • Metastases • P1/2 data • Alveolar Soft Tissue Sarcoma • Brain Cancer • Microsatellite Instability • Neurofibrosarcoma • Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma • MSI • TMB

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

Frontline Systemic Therapeutic Patterns and Outcomes in Rosai-Dorfman Disease: A Multicenter Retrospective Analysis (SOHO 2026) - " Of 44 patients, 27 received targeted therapy (cobimetinib, n = 26; trametinib, n = 1) and 17 received fixedduration chemotherapy (methotrexate, n = 7; cladribine/cytarabine, n = 5; vinblastine/vindesine, n = 3; cyclophosphamide, n = 2). Both chemotherapy and targeted therapy demonstrated clinically meaningful ORR and PFS. Although small sample size prevented statistical comparison, a greater proportion of targeted therapy patients required next-line therapy, reflecting higher discontinuation rates from AEs. While preliminary data suggest both treatment approaches may be effective, larger studies would provide more definitive insights."

Retrospective data • Oncology • BRAF • DNMT3A • KRAS • MAP2K1 • MAP2K2 • NRAS

WHEN SMOKING CESSATION IS NOT ENOUGH: COBIMETINIB FOR PROGRESSIVE PULMONARY LANGERHANS CELL HISTIOCYTOSIS WITH BRAF N486–490DEL (CHEST 2026) - No abstract available

Langerhans Cell Histiocytosis • Respiratory Diseases • Tobacco Cessation • 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

KRAS Mutations in Histiocytic Neoplasms: Mutation Spectrum and Response to MEK Inhibition (SOHO 2026) - "One patient who progressed on cobimetinib subsequently responded to trametinib. KRAS mutations represent an important subset of MAPK alterations in HN and vary by disease subtype. Codon 146 mutations may be associated with improved response to MEKi. Larger cohorts are needed to validate variant-specific predictors of response and guide precision therapy."

Oncology • KRAS

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

Clinical Characteristics and Therapeutic Outcomes of RAF1-Fusion in NSCLC (IASLC-WCLC 2026) - "Stable VCL-RAF1-expressing NIH3T3 cells demonstrated transforming potential by colony formation and showed growth suppression with clinically relevant doses of the MEK inhibitors trametinib and cobimetinib. Conclusions : These findings support VCL-RAF1 as a rare but potentially actionable molecular subtype in NSCLC and provide a translational framework for precision therapeutic strategies."

Clinical • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • BRAF • KRAS • RAF1

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

Improving public cancer care by implementing precision medicine in Norway (clinicaltrialsregister.eu) - P1/2 | N=1000 | Recruiting | Sponsor: Oslo University Hospital HF | N=6000 ➔ 1000

Enrollment change • Oncology

A randomized phase 2 study of combination atezolizumab and varlilumab (CDX-1127) with or without addition of cobimetinib in previously treated unresectable biliary tract cancer. (ASCO 2024) - P2 | "The combination of Atezolizumab and Varlilumab with or without Cobimetinib was safe but did not improve clinical outcomes in advanced stage BTC patients treated in later lines. Though not statistically significant, treatment with CAV demonstrated numerically favorable PFS/OS compared AV among immunotherapy-experienced patients."

Clinical • P2 data • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • CD27 • CD8

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

Myeloma Developing Regimens Using Genomics (MyDRUG): Longitudinal Single-Cell Transcriptional Landscape of the Myeloma and Immune Microenvironment in Relapsed/Refractory Multiple Myeloma Patients Treated with MEK-Inhibitor, Cobimetinib (ASH 2022) - P1/2 | "Cobimetinib plus Dexamethasone were administered for two 28-day cycles followed by the addition of an Ixazomib, Pomalidomide and Dexamethasone (IPd) backbone therapy for all subsequent treatment cycles until disease progression. After exposure to Cobimetinib, the plasma cell clusters that expressed higher levels of this MAPK signature decreased in proportion relative to clusters with lower expression of MAPK. In summary, here we report on our initial observations of dynamic transcriptional changes in specific immune and myeloma cell compartments that are associated with targeting the MAPK pathway in the MyDrug C1 sub-protocol."

Clinical • Hematological Malignancies • Melanoma • Multiple Myeloma • Oncology • Solid Tumor • BRAF • CD14 • CDKN2C • FGFR3 • HLA-DRB1 • IDH2 • KRAS • NRAS • SDC1

Large-scale pleiotropic analysis across cancers reveals shared genetic mechanisms and identifies novel functional genes. (PubMed, Brief Bioinform) - "Importantly, drug sensitivity assays demonstrated that bosutinib and cobimetinib exhibited promising therapeutic potential in breast cancer cell lines. Finally, we developed the PleioCancer database (https://gonglab.hzau.edu.cn/PleioCancer/), providing a comprehensive resource for cancer pleiotropy research. These findings have important implications for carcinogenesis cancer, prevention and treatment."

Journal • Breast Cancer • Oncology • Solid Tumor • FANCA

Nivolumab monotherapy or combination with ipilimumab with or without cobimetinib in previously treated patients with pancreatic adenocarcinoma (CheckMate 032). (PubMed, J Immunother Cancer) - "Nivolumab with or without ipilimumab did not elicit objective responses in previously treated patients with advanced pancreatic adenocarcinoma, although three confirmed partial responses and manageable safety were observed with cobimetinib-containing triplet therapy. The small sample size and differences in baseline disease-specific characteristics between arms limit interpretation of these results."

Journal • Monotherapy • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

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

Phase II Trial of Atezolizumab Plus Cobimetinib in PD-(L)1 Inhibitor Resistant NSCLC: NCI ETCTN Study 10166 (IASLC-WCLC 2024) - P2 | "Analyses of paired biopsies is ongoing. Conclusions : Though durable responses were noted in both KRAS mutant and wild type cohorts, the combination of atezolizumab plus cobimetinib displayed minimal clinical activity in PD-(L)1 resistant NSCLC."

IO biomarker • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

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