^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    DRUG:

    Cotellic (cobimetinib)

    i
    Other names: GDC-0973, RG-7420, XL518, RO 5514041, RG7421, XL-518, R-7421, RO-5514041
    Company:
    Exelixis, Roche
    Drug class:
    MEK1 inhibitor
    Related drugs:
    9d
    A Phase IB/II Study of Alectinib Combined With Cobimetinib in Advanced ALK-Rearranged (ALK+) NSCLC (clinicaltrials.gov)
    P1/2, N=16, Active, not recruiting, Massachusetts General Hospital | Recruiting --> Active, not recruiting | N=31 --> 16 | Trial completion date: Nov 2024 --> Jan 2027 | Trial primary completion date: Nov 2022 --> Jan 2025
    Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • Metastases
    |
    ALK rearrangement
    |
    Alecensa (alectinib) • Cotellic (cobimetinib)
    16d
    BOUQUET: A Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors (clinicaltrials.gov)
    P2, N=550, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    ER (Estrogen receptor)
    |
    Avastin (bevacizumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Ibrance (palbociclib) • paclitaxel • Kadcyla (ado-trastuzumab emtansine) • Cotellic (cobimetinib) • Verzenio (abemaciclib) • cyclophosphamide • letrozole • ipatasertib (RG7440) • triptorelin • goserelin acetate • giredestrant (GDC-9545) • inavolisib (GDC-0077)
    23d
    BFAST: A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)
    P2/3, N=1000, Recruiting, Hoffmann-La Roche | Trial completion date: Apr 2024 --> Aug 2028 | Trial primary completion date: Apr 2024 --> Aug 2028
    Trial completion date • Trial primary completion date • Tumor mutational burden • Metastases
    |
    BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden)
    |
    Avastin (bevacizumab) • cisplatin • Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • carboplatin • gemcitabine • Rozlytrek (entrectinib) • docetaxel • Alecensa (alectinib) • Cotellic (cobimetinib) • pemetrexed • divarasib (RG6330)
    27d
    NCI-2018-01399: Cobimetinib and Atezolizumab in Treating Participants With Advanced or Refractory Rare Tumors (clinicaltrials.gov)
    P2, N=49, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | N=71 --> 49 | Trial completion date: Jan 2025 --> Apr 2024 | Trial primary completion date: Jan 2025 --> Apr 2024
    Trial completion • Enrollment change • Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Tecentriq (atezolizumab) • Cotellic (cobimetinib)
    1m
    Rosai-Dorfman Disease, Presenting as a Right Atrial Mass with Involvement of the Tricuspid Valve in a 54-Year-Old Woman. (PubMed, Am J Case Rep)
    Obtaining tissue for diagnosis can be challenging in this organ. Treatment is challenging when the mass cannot be extracted completely, like in our case, because other forms of therapies are not well studied and warrant further investigation, such as cobimetinib, which is a MEK pathway inhibitor approved in 2022 by the US Food and Drug Administration for histiocytic neoplasms.
    Journal
    |
    CD68 (CD68 Molecule)
    |
    Cotellic (cobimetinib)
    1m
    NAUTIKA1: A Study of Multiple Therapies in Biomarker-Selected Patients With Resectable Stages IB-III Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=146, Recruiting, Genentech, Inc. | N=85 --> 146
    Enrollment change
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
    |
    PD-L1 expression • KRAS mutation • KRAS G12C • BRAF mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • ALK fusion • RET mutation • ROS1 fusion • KRAS G12 • ALK-ROS1 fusion
    |
    Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • Rozlytrek (entrectinib) • Alecensa (alectinib) • Cotellic (cobimetinib) • Gavreto (pralsetinib) • divarasib (RG6330)
    2ms
    NAUTIKA1: A Study of Multiple Therapies in Biomarker-Selected Patients With Resectable Stages IB-III Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=85, Recruiting, Genentech, Inc. | Trial primary completion date: Mar 2024 --> Dec 2025
    Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
    |
    PD-L1 expression • KRAS mutation • KRAS G12C • BRAF mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • ALK fusion • RET mutation • ROS1 fusion • KRAS G12 • ALK-ROS1 fusion
    |
    Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • Rozlytrek (entrectinib) • Alecensa (alectinib) • Cotellic (cobimetinib) • Gavreto (pralsetinib) • divarasib (RG6330)
    2ms
    Atezolizumab With or Without Cobimetinib in Treating Patients With Metastatic Bile Duct Cancer That Cannot Be Removed by Surgery or Gallbladder Cancer (clinicaltrials.gov)
    P2, N=86, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Feb 2024
    Trial completion • Trial completion date • Combination therapy • IO biomarker • Surgery • Metastases
    |
    PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • CD4 (CD4 Molecule)
    |
    PD-L1 expression
    |
    Tecentriq (atezolizumab) • Cotellic (cobimetinib)
    2ms
    Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial (clinicaltrials.gov)
    P1, N=2, Terminated, OHSU Knight Cancer Institute | Active, not recruiting --> Terminated; Low accrual
    Trial termination
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab) • Avastin (bevacizumab) • Venclexta (venetoclax) • Lynparza (olaparib) • Mekinist (trametinib) • erlotinib • Gilotrif (afatinib) • Yervoy (ipilimumab) • Ibrance (palbociclib) • dasatinib • Zelboraf (vemurafenib) • Tafinlar (dabrafenib) • carboplatin • Imfinzi (durvalumab) • sorafenib • Rozlytrek (entrectinib) • imatinib • Sutent (sunitinib) • everolimus • Nerlynx (neratinib) • Iclusig (ponatinib) • Kadcyla (ado-trastuzumab emtansine) • Cotellic (cobimetinib) • Lorbrena (lorlatinib) • Lenvima (lenvatinib) • bortezomib • doxorubicin hydrochloride • capecitabine • Verzenio (abemaciclib) • Xtandi (enzalutamide capsule) • Cabometyx (cabozantinib tablet) • albumin-bound paclitaxel • Stivarga (regorafenib) • abiraterone acetate • oxaliplatin • Aliqopa (copanlisib) • Vizimpro (dacomitinib) • Zydelig (idelalisib) • daunorubicin • Zolinza (vorinostat) • Idhifa (enasidenib) • Farydak (panobinostat) • Erivedge (vismodegib) • Nubeqa (darolutamide) • bicalutamide • leucovorin calcium • cabazitaxel • Vesanoid (tretinoin) • fluorouracil topical
    2ms
    My Pathway: A Study Evaluating Herceptin/Perjeta, Tarceva, Zelboraf/Cotellic, Erivedge, Alecensa, and Tecentriq Treatment Targeted Against Certain Molecular Alterations in Participants With Advanced Solid Tumors (clinicaltrials.gov)
    P2, N=673, Completed, Genentech, Inc. | Phase classification: P2a --> P2
    Phase classification
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • PTCH1 (Patched 1) • SMO (Smoothened Frizzled Class Receptor)
    |
    EGFR mutation • HER-2 overexpression • BRAF mutation • HER-2 amplification • BRAF V600 • ALK rearrangement • ALK mutation • SMO mutation
    |
    Herceptin (trastuzumab) • Tecentriq (atezolizumab) • erlotinib • Zelboraf (vemurafenib) • Alecensa (alectinib) • Perjeta (pertuzumab) • Cotellic (cobimetinib) • Erivedge (vismodegib)
    2ms
    Neoadjuvant cobimetinib and atezolizumab with or without vemurafenib for high-risk operable Stage III melanoma: the Phase II NeoACTIVATE trial. (PubMed, Nat Commun)
    No surgical delays nor progression to regional unresectability occurred (secondary outcome). Peripheral blood CD8 + TCM cell expansion associated with favorable pathologic responses (exploratory outcome).
    P2 data • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    BRAF (B-raf proto-oncogene) • CD8 (cluster of differentiation 8)
    |
    BRAF mutation • BRAF wild-type
    |
    Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • Cotellic (cobimetinib)
    2ms
    Venetoclax and Cobimetinib in Relapsed/Refractory AML: A Phase 1b Trial. (PubMed, Clin Lymphoma Myeloma Leuk)
    Venetoclax-cobimetinib showed limited preliminary efficacy similar to single-agent venetoclax, but with added toxicity. Our findings will inform future trials of BCL-2/MAPK pathway inhibitor combinations.
    P1 data • Journal • IO biomarker
    |
    TP53 (Tumor protein P53) • BCL2L1 (BCL2-like 1)
    |
    TP53 mutation • BCL2L1 mutation
    |
    Venclexta (venetoclax) • Cotellic (cobimetinib)
    2ms
    A Study to Evaluate the Safety and Activity of Belvarafenib as a Single Agent and in Combination With Either Cobimetinib or Cobimetinib Plus Nivolumab in Patients With NRAS-mutant Advanced Melanoma. (clinicaltrials.gov)
    P1, N=65, Active, not recruiting, Genentech, Inc. | Recruiting --> Active, not recruiting | N=128 --> 65
    Enrollment closed • Enrollment change • Combination therapy • IO biomarker • Metastases
    |
    NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation
    |
    Opdivo (nivolumab) • Cotellic (cobimetinib) • belvarafenib (RG6185)
    3ms
    Morpheus Lung: A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer) (clinicaltrials.gov)
    P1/2, N=675, Recruiting, Hoffmann-La Roche | N=470 --> 675 | Trial completion date: Nov 2026 --> Sep 2027 | Trial primary completion date: Aug 2025 --> Jun 2026
    Enrollment change • Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • carboplatin • gemcitabine • docetaxel • Cotellic (cobimetinib) • pemetrexed • ipatasertib (RG7440) • Trodelvy (sacituzumab govitecan-hziy) • Actemra IV (tocilizumab) • tiragolumab (RG6058) • camonsertib (RP-3500) • cibisatamab (RG7802) • ciforadenant (CPI-444) • zanzalintinib (XL092)
    3ms
    T3011 in Combination With Cobimetinib in Patients With Advanced Melanoma (clinicaltrials.gov)
    P2, N=68, Suspended, ImmVira Pharma Co. Ltd | Phase classification: P2a --> P2 | Trial completion date: Jan 2026 --> Jan 2027 | Not yet recruiting --> Suspended | Trial primary completion date: Dec 2025 --> Dec 2026
    Phase classification • Trial completion date • Trial suspension • Trial primary completion date • Combination therapy • Metastases
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF V600E • BRAF V600 • BRAF V600K • RAS mutation • BRAF V600E + BRAF V600K
    |
    Cotellic (cobimetinib) • T3011
    3ms
    Promising response to vemurafenib and cobimetinib treatment for BRAF V600E mutated craniopharyngioma: a case report and literature review. (PubMed, CNS Oncol)
    After initial surgery with subtotal resection, the patient demonstrated durable response to targeted BRAF and MEK inhibitor therapy with vemurafenib and cobimetinib. Our report suggests that targeted therapy may reduce the need for radiation and impact surgical interventions in select cases.
    Review • Journal
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF V600E • BRAF V600
    |
    Zelboraf (vemurafenib) • Cotellic (cobimetinib)
    3ms
    Tricotel: A Study Evaluating the Safety and Efficacy of Cobimetinib Plus Atezolizumab in BRAFV600 Wild-type Melanoma With Central Nervous System Metastases and Cobimetinib Plus Atezolizumab and Vemurafenib in BRAFV600 Mutation-positive Melanoma With Central Nervous System Metastases (clinicaltrials.gov)
    P2, N=80, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed
    Trial completion
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF V600
    |
    Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • Cotellic (cobimetinib)
    3ms
    Safety and Tolerability of ABM-1310 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=112, Active, not recruiting, ABM Therapeutics Corporation | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF V600E • BRAF mutation • BRAF V600 • BRAF positive
    |
    Cotellic (cobimetinib) • ABM-1310
    3ms
    Primary results and characterization of patients with exceptional outcomes in a phase 1b study combining PARP and MEK inhibition, with or without anti-PD-L1, for BRCA wild-type, platinum-sensitive, recurrent ovarian cancer. (PubMed, Cancer)
    Chemotherapy-free doublet and triplet therapy demonstrated encouraging activity, including among patients who had BRCA wild-type, HRDsig-positive or HRDsig-negative PSROC harboring NF1 or MKNK1 mutations.
    P1 data • Journal • BRCA Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    HRD (Homologous Recombination Deficiency) • NF1 (Neurofibromin 1) • BRCA (Breast cancer early onset) • MKNK1 (MAPK Interacting Serine/Threonine Kinase 1)
    |
    HRD • NF1 mutation • BRCA wild-type • BRCA mutation • HRD signature
    |
    FoundationOne® CDx
    |
    Tecentriq (atezolizumab) • Cotellic (cobimetinib) • Zejula (niraparib)
    3ms
    Cancer Molecular Screening and Therapeutics (MoST) Program and ASPiRATION subprogram, Addendum 12 – substudies 27-30: Vemurafenib and Cobimetinib (ACTRN12620000861954)
    P2, N=64, Active, not recruiting, University of Sydney | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF V600E • BRAF V600 • BRAF positive
    |
    Zelboraf (vemurafenib) • Cotellic (cobimetinib)
    3ms
    Vemurafenib and Cobimetinib in Treating Patients With BRAF V600E Mutation Positive Craniopharyngioma (clinicaltrials.gov)
    P2, N=36, Recruiting, Alliance for Clinical Trials in Oncology | Trial primary completion date: Oct 2023 --> Oct 2024
    Trial primary completion date
    |
    CYP1A2 (Cytochrome P450, family 1, subfamily A, polypeptide 2)
    |
    BRAF V600E • BRAF V600 • BRAF positive
    |
    Zelboraf (vemurafenib) • Cotellic (cobimetinib)
    3ms
    Cobimetinib In Extracranial Arteriovenous Malformations (COBI-AVM Study) (clinicaltrials.gov)
    P2, N=17, Recruiting, University of Arkansas | Trial completion date: Dec 2023 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    Cotellic (cobimetinib)
    3ms
    SMMART Adaptive Clinical Treatment (ACT) Trial (clinicaltrials.gov)
    P1, N=0, Withdrawn, OHSU Knight Cancer Institute | N=25 --> 0 | Not yet recruiting --> Withdrawn
    Enrollment change • Trial withdrawal
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    |
    BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • EGFR positive
    |
    Avastin (bevacizumab) • Herceptin (trastuzumab) • Lynparza (olaparib) • Tecentriq (atezolizumab) • Ibrance (palbociclib) • Zelboraf (vemurafenib) • carboplatin • Rozlytrek (entrectinib) • Alecensa (alectinib) • Kadcyla (ado-trastuzumab emtansine) • Cotellic (cobimetinib) • capecitabine • Piqray (alpelisib) • Zejula (niraparib) • albumin-bound paclitaxel • fulvestrant • irinotecan • Halaven (eribulin mesylate) • letrozole • vinorelbine tartrate • Herzuma (trastuzumab-pkrb) • anastrozole • Erivedge (vismodegib) • Trazimera (trastuzumab-qyyp) • Phesgo (pertuzumab/trastuzumab/hyaluronidase-zzxf)
    4ms
    IN10018 Monotherapy and Combination Therapy for Metastatic Melanoma (clinicaltrials.gov)
    P1, N=120, Recruiting, InxMed (Shanghai) Co., Ltd. | Trial completion date: Jun 2024 --> Sep 2024 | Trial primary completion date: Dec 2023 --> Jun 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation • NRAS Q61 • NRAS G12 • NRAS G13
    |
    Tecentriq (atezolizumab) • Cotellic (cobimetinib) • ifebemtinib (IN10018)
    4ms
    Atezolizumab With or Without Cobimetinib in Treating Patients With Metastatic Bile Duct Cancer That Cannot Be Removed by Surgery or Gallbladder Cancer (clinicaltrials.gov)
    P2, N=86, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2024 --> Dec 2024
    Trial completion date • Combination therapy • IO biomarker • Surgery • Metastases
    |
    PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • CD4 (CD4 Molecule)
    |
    PD-L1 expression
    |
    Tecentriq (atezolizumab) • Cotellic (cobimetinib)
    4ms
    XL888 + Vemurafenib + Cobimetinib for Unresectable BRAF Mutated Stage III/IV Melanoma (clinicaltrials.gov)
    P1, N=26, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute
    Trial completion date
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF mutation • BRAF V600
    |
    Zelboraf (vemurafenib) • Cotellic (cobimetinib) • XL888
    4ms
    Combined PDE4+MEK inhibition shows antiproliferative effects in NRASQ61 mutated melanoma preclinical models. (PubMed, Melanoma Res)
    A significant ex vivo inhibition of proliferation with the combination of roflumilast+cobimetinib was observed compared to dimethyl sulfoxyde control in both models (51 and 67%). To decipher molecular mechanisms underlying this effect, we performed transcriptomic analyses and revealed a decrease in MKI67, RAF1 and CCND1 expression under bitherapy. Our findings strengthen the therapeutic interest of PDE4 inhibitors and support further experiments to evaluate this approach in metastatic melanoma.
    Preclinical • Journal
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CCND1 (Cyclin D1) • PDX1 (Pancreatic And Duodenal Homeobox 1)
    |
    NRAS mutation • NRAS Q61 • CCND1 expression
    |
    Cotellic (cobimetinib)
    4ms
    NCI-2018-01399: Cobimetinib and Atezolizumab in Treating Participants With Advanced or Refractory Rare Tumors (clinicaltrials.gov)
    P2, N=71, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Tecentriq (atezolizumab) • Cotellic (cobimetinib)
    4ms
    The Predictive Value of FDG PET/CT for Determining Progression-Free Survival in Advanced Stage III-IV BRAF-Mutated Melanoma Patients Treated With Targeted Therapy-What Can Be Learned From Progression? (PubMed, Clin Nucl Med)
    This study shows that PERCIST response assessment at week 7 is predictive for PFS, regardless of LDH. At 2 weeks, patients with CMR have longer PFS than patients with non-CMR, but different PET parameters should be investigated to further evaluate the added value of early 18F-FDG PET/CT. Disease progression on PET/CT is predominated by progression of known metastases, and new 18F-FDG-avid lesions during BRAF/MEKi are not automatically a sign of recurrent disease.
    Journal • FDG PET • Metastases
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF mutation
    |
    Zelboraf (vemurafenib) • Cotellic (cobimetinib)
    5ms
    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
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF V600E • BRAF mutation • BRAF K601E • BRAF T599 • BRAF K601
    |
    Zelboraf (vemurafenib) • Cotellic (cobimetinib)
    5ms
    Enasidenib in Combination With Cobimetinib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov)
    P1, N=15, Recruiting, City of Hope Medical Center | Phase classification: P1b --> P1 | Trial completion date: Mar 2024 --> May 2025 | Trial primary completion date: Mar 2024 --> May 2025
    Phase classification • Trial completion date • Trial primary completion date • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)
    |
    KRAS mutation • NRAS mutation • IDH2 mutation • NF1 mutation • RAS mutation • CBL mutation • IDH2 R140 • IDH2 R172
    |
    Cotellic (cobimetinib) • Idhifa (enasidenib)
    5ms
    CheckMate142: A Study of Nivolumab Alone or Nivolumab Combination Therapy in Colon Cancer That Has Come Back or Has Spread (clinicaltrials.gov)
    P2, N=385, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Dec 2024 --> Feb 2024
    Trial completion date • Combination therapy • Metastases
    |
    MSI (Microsatellite instability)
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • Cotellic (cobimetinib) • Darzalex (daratumumab) • relatlimab (BMS-986016)
    5ms
    CheckMate 032: A Study of Nivolumab by Itself or Nivolumab Combined With Ipilimumab in Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=1163, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Dec 2023 --> May 2024
    Trial completion date • Metastases
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • Cotellic (cobimetinib)
    5ms
    BRAF and MEK inhibitor combinations induce potent molecular and immunological effects in NRAS-mutant melanoma cells: Insights into mode of action and resistance mechanisms. (PubMed, Int J Cancer)
    In our study, the MEKi binimetinib, cobimetinib and trametinib combined with the BRAF inhibitors (BRAFi) encorafenib, vemurafenib and dabrafenib were investigated for their ability to inhibit proliferation, induce apoptosis and alter the expression of immune modulatory molecules in sensitive NRAS-mutant melanoma cells using two- and three-dimensional cell culture models as well as RNA sequencing analyses. The BRAFi/MEKi-resistant, NRAS-mutant melanoma cells counteracted the molecular and immunological effects of BRAFi/MEKi by upregulating downstream mitogen-activated protein kinase pathway molecules, inhibiting apoptosis and promoting immune escape mechanisms. Together, our study reveals potent molecular and immunological effects of BRAFi/MEKi in sensitive NRAS-mutant melanoma cells that may be exploited in new combinational treatment strategies for patients with NRAS-mutant melanoma.
    Journal • IO biomarker
    |
    NRAS (Neuroblastoma RAS viral oncogene homolog) • ICOS (Inducible T Cell Costimulator)
    |
    NRAS mutation
    |
    Mekinist (trametinib) • Zelboraf (vemurafenib) • Tafinlar (dabrafenib) • Cotellic (cobimetinib) • Mektovi (binimetinib) • Braftovi (encorafenib)
    5ms
    Expanding immunotherapy options in cholangiocarcinoma: Role of CD27 agonist in combination with PD-L1 and MEK inhibition on antitumor effect and CD8+ T cells. (ASCO-GI 2024)
    Immune cells from pmel-1 mice were isolated, activated with gp100, and cultured in vitro with 100 IU/mL IL-2 and single, dual, or triple therapy with CD27Ag, cobimetinib (MEKi) and/or αPD-L1... CD27 agonism prevents the impairment of T cell activation that was mediated by MEKi. Moreover, this CD27Ag/MEKi/PDL1i triple therapy bolstered trafficking of T cells with stem-like, effector, or resident memory properties, in turn enhancing the antitumor response. This therapy is being evaluated in metastatic CCA patients in an ongoing Phase II clinical trial.
    Combination therapy • PD(L)-1 Biomarker • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • CD69 (CD69 Molecule) • IL2 (Interleukin 2) • CD27 (CD27 Molecule) • ITGAE (Integrin Subunit Alpha E)
    |
    Cotellic (cobimetinib)
    5ms
    Testing the Combination of APG-1252 (Pelcitoclax) and Cobimetinib in Recurrent Ovarian and Endometrial Cancers (clinicaltrials.gov)
    P1, N=42, Recruiting, National Cancer Institute (NCI) | Initiation date: Feb 2024 --> Sep 2023
    Trial initiation date
    |
    BRAF (B-raf proto-oncogene) • BCL2L1 (BCL2-like 1)
    |
    Cotellic (cobimetinib) • pelcitoclax (APG-1252)
    5ms
    A Study to Evaluate the Safety and Activity of Belvarafenib as a Single Agent and in Combination With Either Cobimetinib or Cobimetinib Plus Nivolumab in Patients With NRAS-mutant Advanced Melanoma. (clinicaltrials.gov)
    P1, N=128, Recruiting, Genentech, Inc. | Trial completion date: Sep 2024 --> Nov 2025 | Trial primary completion date: Nov 2023 --> Nov 2025
    Trial completion date • Trial primary completion date • Combination therapy • IO biomarker • Metastases
    |
    NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation
    |
    Opdivo (nivolumab) • Cotellic (cobimetinib) • belvarafenib (RG6185)
    5ms
    Disseminated Xanthogranuloma with BRAF Gene Fusion and Profound Response to MEK Inhibitor Therapy (ASH 2023)
    Regrettably, following the cessation of Trametinib, the patient's lesions rapidly progressed, and her disease worsened beyond the pre-treatment state. Taking into account the 10% PDL-1 positivity, immunotherapy with Pembrolizumab was commenced, resulting in partial improvement...Consequently, Cobimetinib was discontinued, and a continuously dosed MEK inhibitor, Binimetinib, was cautiously administered at a lower dose to mitigate the risk of cardiotoxicity... To our knowledge, this is the first clinical trial documenting MEK inhibition for a patient with xanthoma disseminatum harboring a BRAF fusion. Seeking to target downstream of BRAF, MEK inhibition demonstrated a dramatic response, with rapid relapse upon cessation, supporting a central oncogenic role for BRAF fusion. Further studies should explore alterations in the RAS-BRAF-ERK pathway in nLCH and consider clinical trials with MEK inhibitors.
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden)
    |
    PD-L1 expression • BRAF mutation • BRAF fusion
    |
    Keytruda (pembrolizumab) • Mekinist (trametinib) • Cotellic (cobimetinib) • Mektovi (binimetinib)
    5ms
    MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov)
    P1/2, N=340, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    PD-L1 (Programmed death ligand 1)
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • gemcitabine • 5-fluorouracil • Cotellic (cobimetinib) • albumin-bound paclitaxel • oxaliplatin • leucovorin calcium • Actemra IV (tocilizumab) • tiragolumab (RG6058) • etrumadenant (AB928) • pegvorhyaluronidase alfa (PEGPH20) • Aphexda (motixafortide) • selicrelumab (RG7876) • simlukafusp alfa (RG7461)
    5ms
    Targeting RAS-ERK pathway alterations with MEK inhibitors to improve chemosensitivity in high grade serous ovarian cancers. (PubMed, Gynecol Oncol)
    MEK inhibitors block RAS-ERK pathways in platinum resistant HGSOC cells and PDOs. MEK inhibitors with carboplatin have select synergistic effects which may indicate a strategy to improve platinum sensitivity.
    Journal
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • NF1 (Neurofibromin 1) • FOXM1 (Forkhead Box M1)
    |
    NF1 mutation • MYC expression
    |
    Mekinist (trametinib) • carboplatin • Cotellic (cobimetinib)
    6ms
    Targeted PARP or MEK/ERK Inhibition in Patients With Pancreatic Cancer (clinicaltrials.gov)
    P1, N=80, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Feb 2026 --> Feb 2028 | Trial primary completion date: Jun 2024 --> Jun 2026
    Trial completion date • Trial primary completion date
    |
    UGT1A1 (UDP glucuronosyltransferase family 1 member A1) • CD4 (CD4 Molecule)
    |
    UGT1A1*1*1
    |
    Lynparza (olaparib) • Cotellic (cobimetinib) • onvansertib (PCM-075) • temuterkib (LY3214996)
    6ms
    Effectiveness, safety and utilization of cobimetinib and vemurafenib in patients with BRAF V600 mutant melanoma with and without cerebral metastasis under real-world conditions in Germany: the non-interventional study coveNIS. (PubMed, Melanoma Res)
    In conclusion, the OS rates in Cohort A and Cohort B of coveNIS are in line with the OS data from other trials with BRAF/MEK inhibitors for mM. No new safety signals were observed.
    Observational data • Journal • Real-world evidence • Real-world
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF mutation • BRAF V600
    |
    Zelboraf (vemurafenib) • Cotellic (cobimetinib)