Cotellic (cobimetinib) / Exelixis, Roche - LARVOL DELTA

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

NeoACTIVATE: Vemurafenib, Cobimetinib, Atezolizumab, and Tiragolumab in Treating Patients With High-Risk Stage III Melanoma (clinicaltrials.gov) - P2 | N=59 | Active, not recruiting | Sponsor: Mayo Clinic | Trial completion date: Jun 2025 ➔ Nov 2027 | Trial primary completion date: Jun 2025 ➔ Nov 2027

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

CUPISCO: A Phase II Randomized Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site (clinicaltrials.gov) - P2 | N=528 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Nov 2024

Trial completion • Trial completion date • Oncology

Cobimetinib In Extracranial Arteriovenous Malformations (COBI-AVM Study) (clinicaltrials.gov) - P2 | N=17 | Active, not recruiting | Sponsor: University of Arkansas | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2026 ➔ Aug 2025 | Trial primary completion date: Dec 2026 ➔ Aug 2025

Enrollment closed • Trial completion date • Trial primary completion date • Cardiovascular • CNS Disorders • Giant Cell Arteritis

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

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

In Vitro Drug Profiling to Guide Treatment for Relapse/Refractory AML (ASH 2024) - "Significant correlation was observed among drugs of the same classes, for example between inhibitors of PARP (e.g. niraparib-talazoparib, r=0.78, p=1.3e-22), proteasome (e.g. bortezomib-ixazomib, r=0.90, p=4.2e-36), JAK (ruxolitinib-tofacitinib, r=0.91, p=8.3e-35), MEK (cobimetinib-trametinib, p=0.93, p=8.8e-47) and CDK (abemaciclib-palbociclib, p=0.56, p=2.7e-10), confirming that the readout is biologically meaningful. Intriguingly, there were unexpected correlations between specific pairs of drugs of different classes, for instance homoharringtonine (protein translation inhibitor)-abemaciclib (CDK inhibitor) (r=0.65, p=4.3e-17) and between specific gene mutations and drug sensitivity was observed, e.g. sensitivity of CEBPAbZIP mutated samples to PARP inhibitors (p=0.00156), and of AML with inv(16) to MEK inhibitors (p=0.0016)...Drug response to daunorubicin showed good prediction of chemo-resistance in patients who had non-remission after "7+3" (ROC curve AUC..."

Preclinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • ANXA5 • FLT3

Immunological Insights into H Syndrome: A French National Cohort Study of 33 Patients Highlighting Auto-Inflammatory Manifestations (EULAR 2025) - "However, MEK inhibitors, such as Cobimetinib, demonstrated superior results in addressing organ infiltration and proliferative lesions in a smaller group of patients (n=5), achieving complete responses in cases where IL-6 antagonists provided only partial relief or where symptoms reappeared after prolonged treatment... This study expands the clinical spectrum of H syndrome, underscoring its classification as both a genetic histiocytosis and a multisystem inflammatory disorder. It highlights autoimmune features, potential immunodeficiency, and a predisposition to fibrosis, which contribute to significant morbidity and mortality. Promising therapeutic options, including MEK inhibitors and IL-6 antagonists, offer hope for better disease management and improved patient outcomes."

Clinical • ANCA Vasculitis • Anemia • Dermatology • Diabetes • Fibrosis • Genetic Disorders • Hematological Disorders • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Musculoskeletal Diseases • Myositis • Ocular Inflammation • Ophthalmology • Otorhinolaryngology • Rare Diseases • Renal Disease • Respiratory Diseases • Rheumatology • Sjogren's Syndrome • Uveitis • Vasculitis • IL6 • MAP2K1 • NRAS

Enasidenib in Combination With Cobimetinib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=3 | Suspended | Sponsor: City of Hope Medical Center | N=15 ➔ 3 | Trial completion date: May 2025 ➔ May 2027 | Recruiting ➔ Suspended | Trial primary completion date: May 2025 ➔ May 2027

Enrollment change • Trial completion date • Trial primary completion date • Trial suspension • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BRAF • IDH2 • KRAS • NF1 • NRAS • PTPN11

ETCTN 10476: Testing A New Combination of Anti-cancer Immune Therapies, Atezolizumab and CDX-1127 (Varlilumab) With or Without the Addition of a Third Anti-cancer Drug, Cobimetinib, for Advanced-Stage Biliary Tract Cancer (clinicaltrials.gov) - P2 | N=57 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jul 2025 ➔ Apr 2026

Trial completion date • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Liver Cancer • Oncology • Solid Tumor

TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer (clinicaltrials.gov) - P2 | N=4200 | Recruiting | Sponsor: American Society of Clinical Oncology | Trial completion date: Jun 2027 ➔ Dec 2028 | Trial primary completion date: Jun 2026 ➔ Dec 2027

Trial completion date • Trial primary completion date • Tumor mutational burden • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • BRAF

Adverse effects of systemic advanced melanoma therapies-do BRAF/MEK inhibitors increase the incidence of mesenteric panniculitis? (PubMed, Eur Radiol) - "Question BRAF/MEK and immune checkpoint inhibitors have revolutionized melanoma treatment but are associated with various side effects, yet data regarding the development of mesenteric panniculitis are scarce. Findings BRAF/MEK inhibitor treatment is associated with a significantly higher rate of mesenteric panniculitis compared to immune checkpoint inhibitor treatment in advanced melanoma. Clinical relevance BRAF/MEK inhibitor-treated patients are at risk for development of mesenteric panniculitis. As this benign finding can mimic or conceal malignancy, awareness of it is important especially in these patients."

Adverse events • Journal • Melanoma • Oncology • Solid Tumor • CTLA4

Cost per outcome of nivolumab + relatlimab vs BRAF + MEK inhibitor combinations for first-line treatment of BRAF-mutant advanced melanoma. (PubMed, J Manag Care Spec Pharm) - "To compare the health care costs, cost per progression-free life-year (PFLY), and cost per life-year (LY) of NIVO + RELA vs dabrafenib plus trametinib (DAB + TRAM), encorafenib plus binimetinib (ENCO + BINI), and vemurafenib plus cobimetinib (VEM + COBI) as 1L treatment for BRAF-mutated, unresectable or metastatic melanoma...NIVO + RELA showed improved LYs and PFLYs at lower cost than all 3 BRAFi/MEKi comparators over 5 years. These results support the economic value of NIVO + RELA for patients with previously untreated, BRAF-mutated, unresectable or metastatic melanoma."

IO biomarker • Journal • Melanoma • Oncology • Solid Tumor • RELA

Treatment of RAS-associated leukoproliferative disease (RALD) and Rosai-Dorfman disease in a patient with KRAS mutation. (PubMed, Leuk Lymphoma) - No abstract available

Journal • Rare Diseases • KRAS • RAS

Metabolic parameters on baseline and early [18F]FDG PET/CT as a predictive biomarker for resistance to BRAF/MEK inhibition in advanced cutaneous BRAFV600-mutated melanoma. (PubMed, EJNMMI Res) - P2 | "This study supports the use of MTV and TLG as robust predictive markers for PFS in advanced melanoma treated with BRAF/MEK-inhibitors. Monitoring early PET parameters changes can provide valuable insights into therapeutic response and disease progression."

Biomarker • Journal • Melanoma • Oncology • Solid Tumor

Access to current medicines in the treatment of Turkish melanoma patients. (PubMed, J Oncol Pharm Pract) - "In metastatic melanoma patients, BRAF/MEK inhibitor agents, vemurafenib-cobimetinib and dabrafenib-trametinib combination therapies, have been registered and reimbursed in the first-line treatment choice of the disease. Among immunotherapy drugs, ipilimumab and nivolumab as single agents have long been registered and reimbursed for the treatment of relapsed disease after chemotherapy, while pembrolizumab is still registered but not reimbursed...Talimogen laherparepvec and tebentafusp are still not registered...In conclusion, in our country, as in other parts of the world, there are difficulties and limitations in accessing the current treatment of melanoma. The significant survival benefits achieved with modern treatment of the disease are unfortunately hampered by difficulties in accessing treatment."

Journal • Melanoma • Oncology • Solid Tumor

Charting the Course: The Diagnostic Journey for a Patient With a Rare Disease - Erdheim Chester Disease With Pulmonary Involvement (ATS 2025) - "As further testing demonstrated a negative BRAFV600E mutation, the patient was initiated on cobimetinib 40 mg daily...Pulmonary involvement, seen in 43% of cases, often presents with features of interstitial lung disease but does not significantly impact overall prognosis. Recent evidence implicates the BRAFV600E mutation in ECD pathogenesis, suggesting new therapeutic possibilities."

Clinical • Anorexia • Atrial Fibrillation • Cardiovascular • Chronic Obstructive Pulmonary Disease • Fatigue • Immunology • Inflammatory Arthritis • Interstitial Lung Disease • Langerhans Cell Histiocytosis • Lupus • Oncology • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Systemic Lupus Erythematosus • Vasculitis • CCND1 • CD163

Combinatorial screen with standard of care and selected anticancer agents identifies multiple combinations with activity against a panel of patient-derived colorectal organoids (AACR 2025) - "Following compound addition, organoid growth was measured by live bright field imaging every 24 h and cell viability was determined by CellTiter-Glo 3D at 48 h and 168 h. Modest responses were observed in most models from the combination of leucovorin with 5-FU; however, >1 log of cytotoxicity was observed in only several models. The panel was more responsive to FOLFOX, which was consistent with the sensitivity of models to oxaliplatin. Responses to TAS-102 varied and >1 log of cytotoxicity was observed in several models...Combination of the BCL-2/BCL-xL inhibitor pelcitoclax plus cobimetinib achieved >1 log of cytotoxicity in most organoid models. Combinations of cobimetinib with the EGFR inhibitors erlotinib, afatinib or cetuximab demonstrated synergy in many organoids according to the Bliss independence model and frequently achieved ≥1 log of cytotoxicity...The combination of cobimetinib and MRTX1133 had synergistic activity by Bliss independence in multiple..."

Clinical • Oncology • BCL2 • BCL2L1 • BRAF • KRAS • PIK3CA

Antibody-drug conjugates with novel payloads are enabled by an ultra-high DAR platform (AACR 2025) - "These HER2-targeted biomolecules combined with payloads inhibiting PI3K/mTOR (apitolisib) or MEK (cobimetinib) demonstrate the use of ADCs as precision medicine to selectively target cancer cells via antibody and payload. As shown in Table 1, PI3K pathway mutations can increase the sensitivity to ADCs with apitolisib as a payload, in some cases surpassing the potency of the exatecan derivative DXd in trastuzumab-DXd (DAR8). We will also present data supporting the in vivo safety and efficacy of these ADCs which may provide a novel solution to expand the therapeutic landscape, particularly for HER2-positive cancers."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CTSC • HER-2

MORPHEUS-EC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Cancer (G/GEJ) or Esophageal Cancer (Morpheus-Gastric and Esophageal Cancer) (clinicaltrials.gov) - P1/2 | N=410 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jun 2025 ➔ Sep 2025 | Trial primary completion date: Jun 2025 ➔ Sep 2025

Trial completion date • Trial primary completion date • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2 • PD-L1 • TIGIT

THE EFFICACY AND SAFETY OF LUVOMETINIB (FCN-159) IN PEDIATRIC PATIENTS WITH REFRACTORY/RELAPSED LANGERHANS CELL HISTIOCYTOSIS: A MULTI-CENTER, OPEN-LABEL, SINGLE-ARM PHASE II STUDY (EHA 2025) - P2 | "Current first-line treatment recommended by Histiocyte Society for children with multifocal disease is vinblastine and prednisone. For patients with risk-organ involvement, additional 6-mercaptopurine is also used as maintenance therapy...While cobimetinib has been approved for the treatment of adult patients, it has not yet been approved for pediatric patients... The preliminary study results showed that luvometinib was highly efficacious for pediatric patients with refractory/relapsed LCH. In addition, luvometinib was well tolerated, without TRAEs-induced discontinuation reported. Trial Information: NCT05997602, CTR20232238."

Clinical • P2 data • Anemia • Dermatitis • Dermatology • Genetic Disorders • Hematological Disorders • Immunology • Infectious Disease • Langerhans Cell Histiocytosis • Neurofibromatosis • Pediatrics • Rare Diseases • Solid Tumor • ARAF • BRAF • CD1a

A Diagnosis Not to Be Missed (ESPE-ESE 2025) - "Initial steroid treatment with dexamethasone provided partial improvement of vision and interruption of deterioration...The patient was initiated on a targeted monoclonal treatment combining vemurafenib and cobimetinib, BRAF/MEK inhibitors. The patient had an improvement in vision and the repeat MRI head from January 2025 demonstrated early response to treatment. In conclusion, the case presented demonstrate the relevance of the recent changes in the clinical management of suprasellar lesions, for which currently a pathological molecular confirmation is a cardinal step to guarantee the best oncological and functional outcomes."

Brain Cancer • CNS Tumor • Glioma • Metabolic Disorders • Oncology • Ophthalmology • Solid Tumor

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

Anaplastic pleomorphic xanthoastrocytoma with leptomeningeal dissemination presenting with cranial neuropathy in an adult patient: illustrative case. (PubMed, J Neurosurg Case Lessons) - "APXA, an already exceedingly rare primary CNS tumor, can present unusually in older adult patients with concomitant LMD and cranial neuropathy. Advanced genomic profiling can tailor adjuvant therapy. https://thejns.org/doi/10.3171/CASE24768."

Journal • Astrocytoma • Brain Cancer • CNS Disorders • CNS Tumor • Epilepsy • Hematological Disorders • Oncology • Pain • Pediatrics • Pleomorphic Xanthoastrocytoma • ATG7 • TERT

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P3 | N=1000 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology