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Cobimetinib (GDC-0973, RG-7420, XL-518)

Alias: cobimetinib; Cotellic; XL518; XL 518; XL-518; GDC0973; GDC-0973; GDC 0973;RG 7420; RG-7420; RG7420
Cat No.:V0453 Purity: ≥98%
Cobimetinib (formerly GDC0973, RG7420, XL518; trade name Cotellic) is an orally bioavailable and selective small-molecule inhibitor of MEK1 with potential anticancer activity.
Cobimetinib (GDC-0973, RG-7420, XL-518)
Cobimetinib (GDC-0973, RG-7420, XL-518) Chemical Structure CAS No.: 934660-93-2
Product category: MEK
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
2mg
5mg
10mg
25mg
50mg
100mg
250mg
500mg
Other Sizes

Other Forms of Cobimetinib (GDC-0973, RG-7420, XL-518):

  • Cobimetinib hemifumarate
  • Cobimetinib racemate
  • Cobimetinib R-enantiomer
Official Supplier of:
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Top Publications Citing lnvivochem Products
Purity & Quality Control Documentation

Purity: ≥98%

Product Description
Cobimetinib (formerly GDC0973, RG7420, XL518; trade name Cotellic) is an orally bioavailable and selective small-molecule inhibitor of MEK1 with potential anticancer activity. With an IC50 of 4.2 nM, it blocks MEK1. In order to treat melanoma, cobimetinib was given FDA approval in 2015. Extracellular signal-related kinase 2 (ERK2) phosphorylation and activation are inhibited, and tumor cell proliferation is decreased, as a result of GDC-0973's ability to specifically bind to and inhibit the catalytic activity of MEK1.
Biological Activity I Assay Protocols (From Reference)
Targets
MEK1 (IC50 = 4.2 nM)
ln Vitro
Cobimetinib shows strong activity on cell growth inhibtion in a broad panel of tumor types, particularly in BRAF or KRAS mutant cancer cell lines. GDC-0973 causes 888MEL and A2058 cells to lose viability, inhibit certain pathways, and undergo more apoptosis when combined with GDC-0941.[1]
Across all BRAFV600E lines, coadministration of GDC-0973 and vemurafenib significantly increases decreased levels of GLUT-1 on the cellular membrane.[2]
ln Vivo
Cobimetinib (10 mg/kg, p.o.) and GDC-0973 and GDC-0941 together exhibit improved antitumor efficacy in mice with BRAFV600E and KRAS mutant tumors.[1]
Combining GDC-0973 and GDC-0941 results in lower levels of hexokinase II, c-RAF, Ksr, and p-MEK protein in mice with drug-resistant A375 xenografts.[2]
Enzyme Assay
Cobimetinib (GDC-0973, RG7420) is a potent, selective and oral MEK1 inhibitor with an IC50 of 4.2 nM for MEK1.
Cell Assay
For 888MEL and A2058 cells, the EC50 concentrations of cobimetinib (GDC-0973) are 0.2 M and 10 M, respectively. EC50 concentrations of MEK and PI3K inhibitors are applied to melanoma cells for 24 hours (888MEL: 0.05 M GDC-0973, 2.5 M GDC-0941; A2058: 2.5 M GDC-0973, 2.5 M GDC-0941). Cell death brought on by cobimetinib (100 nM) in melanoma with constitutive MAPK activation in A375 cells is restricted by mitochondrial OXPHOS.
Animal Protocol
Female NCR nude mice have had 5 million WM-266-4 melanoma cells intradermally implanted into the hind flank. The cells were resuspended in Hank balanced salt solution. Xenograft mice with tumor volumes of roughly 100 to 120 mm3 are randomly assigned to 4 single dose groups and 4 multiple dose groups on days 11 or 13 following the implantation. Mice in the single dose groups receive a single oral dose of the drug Cobimetinib (GDC-0973, expressed as free base equivalents), vehicle (water for injection USP), 1, 3, or 10 mg/kg one day after randomization and group assignment. For 14 days, mice in the multiple dose groups receive daily oral doses of the GDC-0973 1, 3, or 10 mg/kg, vehicle (water for injection USP), or both. On day 1 (single dose groups) or day 14 (multiple dose groups), plasma and tumor samples (n=3 per time point) are taken from euthanized mice predose and at 2, 4, 8, 16, 24, 72, and 168 hours postdose. Samples are kept until analysis at 80°C. Liquid chromatography/tandem mass spectrometry (LC/MS-MS) is used to assess the concentrations of GDC-0973 in tumor lysates and plasma. The assay's dynamic range is 0.004 to 35 μM.
ADME/Pharmacokinetics
Absorption, Distribution and Excretion
Following oral dosing of 60 mg once daily in cancer patients, the median time to achieve peak plasma levels (Tmax) was 2.4 (range:1–24) hours, geometric mean steady-state AUC0-24h was 4340 ng∙h/mL (61% CV) and Cmax was 273 ng/mL (60% CV). The absolute bioavailability of COTELLIC was 46% (90% CI: 40%, 53%) in healthy subjects. A high‐fat meal (comprised of approximately 150 calories from protein, 250 calories from carbohydrate, and 500–600 calories from fat) had no effect on cobimetinib AUC and Cmax after a single 20 mg COTELLIC was administered to healthy subjects.
Following oral administration of a single 20 mg radiolabeled cobimetinib dose, 76% of the dose was recovered in the feces (with 6.6% as unchanged drug) and 17.8% of the dose was recovered in the urine (with 1.6% as unchanged drug).
The estimated apparent volume of distribution was 806 L in cancer patients based on a population PK analysis.
Following oral administration of COTELLIC 60 mg once daily in cancer patients, the mean apparent clearance (CL/F) was 13.8 L/h (61% CV).
Metabolism / Metabolites
Cobimetinib is mainly metabolized via CYP3A oxidation and UGT2B7 glucuronidation with no major metabolites formed.
Biological Half-Life
Following oral administration of COTELLIC 60 mg once daily in cancer patients, the mean elimination half-life (t1/2) was 44 (range: 23–70) hours.
Toxicity/Toxicokinetics
Hepatotoxicity
Elevations in serum aminotransferase and alkaline phosphatase levels are common during vemurafenib therapy and are even more common when it is combined with cobimetinib, abnormal liver tests occurring in 26% to 70% of treated patients and ALT values rising above 5 times the upper limit of the normal range (ULN) in 6% to 12%. Instances of clinically apparent liver injury with jaundice have also been reported during the clinical trials of cobimetinib and vemurafenib therapy, but the clinical features, course and outcomes of these episodes have not been described in detail. At least one instance of hepatocellular injury with jaundice was included in the initial safety review of cobimetinib. The MAPK pathway inhibitors as a class are often associated with transient serum enzyme elevations and more rarely with instances of clinically apparent liver injury, but the clinical features have not been described and the association with cobimetinib not clearly defined. The rate of clinically significant liver injury and hepatic failure associated with protein kinase inhibitors is increased in patients with preexisting cirrhosis or hepatic impairment due to liver tumor burden.
Likelihood score: D (possible cause of clinically apparent liver injury).
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the clinical use of cobimetinib during breastfeeding. Because cobimetinib is 90% bound to plasma proteins, the amount in milk is likely to be low. However, its half-life is about 44 hours and it might accumulate in the infant. The manufacturer recommends that breastfeeding be discontinued during cobimetinib therapy and for 2 weeks after the last dose.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.
Protein Binding
Cobimetinib is 95% bound to human plasma proteins in vitro, independent of drug concentration.
References

[1]. Cancer Res . 2012 Jan 1;72(1):210-9.

[2] EJNMMI Res . 2012 May 31;2(1):22.

Additional Infomation
Pharmacodynamics
Cobimetinib is a reversible inhibitor of mitogen-activated protein kinase 1 (MAPK)/extracellular signal-regulated kinase 1 (MEK1) and MEK2. Preclinical studies have demonstrated that this agent is effective in inhibiting the growth of tumor cells bearing a BRAF mutation, which has been found to be associated with many tumor types. A threonine-tyrosine kinase and a key component of the RAS/RAF/MEK/ERK signaling pathway that is frequently activated in human tumors, MEK1 is required for the transmission of growth-promoting signals from numerous receptor tyrosine kinases. Cobimetinib is used in combination with vemurafenib because the clinical benefit of a BRAF inhibitor is limited by intrinsic and acquired resistance. Reactivation of the MAPK pathway is a major contributor to treatment failure in BRAF-mutant melanomas, approximately ~80% of melanoma tumors become BRAF-inhibitor resistant due to reactivation of MAPK signaling. BRAF-inhibitor-resistant tumor cells are sensitive to MEK inhibition, therefore cobimetinib and vemurafenib will result in dual inhibition of BRAF and its downstream target, MEK.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C21H21F3IN3O2
Molecular Weight
531.318
Exact Mass
531.063
Elemental Analysis
C, 47.47; H, 3.98; F, 10.73; I, 23.88; N, 7.91; O, 6.02
CAS #
934660-93-2
Related CAS #
Cobimetinib hemifumarate;1369665-02-0;Cobimetinib racemate;934662-91-6;Cobimetinib (R-enantiomer);934660-94-3
PubChem CID
16222096
Appearance
white solid powder
Density
1.7±0.1 g/cm3
Boiling Point
565.9±50.0 °C at 760 mmHg
Flash Point
296.1±30.1 °C
Vapour Pressure
0.0±1.6 mmHg at 25°C
Index of Refraction
1.662
LogP
5.96
Hydrogen Bond Donor Count
3
Hydrogen Bond Acceptor Count
7
Rotatable Bond Count
4
Heavy Atom Count
30
Complexity
624
Defined Atom Stereocenter Count
1
SMILES
C(N1CC([C@H]2NCCCC2)(O)C1)(C1=CC=C(F)C(F)=C1NC1C=CC(I)=CC=1F)=O
InChi Key
BSMCAPRUBJMWDF-KRWDZBQOSA-N
InChi Code
InChI=1S/C21H21F3IN3O2/c22-14-6-5-13(19(18(14)24)27-16-7-4-12(25)9-15(16)23)20(29)28-10-21(30,11-28)17-3-1-2-8-26-17/h4-7,9,17,26-27,30H,1-3,8,10-11H2/t17-/m0/s1
Chemical Name
[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-hydroxy-3-[(2S)-piperidin-2-yl]azetidin-1-yl]methanone
Synonyms
cobimetinib; Cotellic; XL518; XL 518; XL-518; GDC0973; GDC-0973; GDC 0973;RG 7420; RG-7420; RG7420
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~100 mg/mL (~188.2 mM)
Water: <1 mg/mL
Ethanol: ~47 mg/mL (~88.5 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.5 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.


Solubility in Formulation 4: ≥ 2.5 mg/mL (4.71 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

Solubility in Formulation 5: 5% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5mg/mL

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.8821 mL 9.4105 mL 18.8210 mL
5 mM 0.3764 mL 1.8821 mL 3.7642 mL
10 mM 0.1882 mL 0.9411 mL 1.8821 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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g/mol

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
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Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
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Clinical Trial Information
Vemurafenib and Cobimetinib for the Treatment of Patients With High Risk Differentiated Thyroid Carcinoma With BRAFV600E Mutation
CTID: NCT06440850
Phase: Phase 2    Status: Recruiting
Date: 2024-12-02
IN10018 Monotherapy and Combination Therapy for Metastatic Melanoma
CTID: NCT04109456
Phase: Phase 1    Status: Active, not recruiting
Date: 2024-11-29
Bevacizumab and Atezolizumab With or Without Cobimetinib in Treating Patients With Untreated Melanoma Brain Metastases
CTID: NCT03175432
Phase: Phase 2    Status: Active, not recruiting
Date: 2024-11-29
Vemurafenib, Cobimetinib, Atezolizumab, and Tiragolumab in Treating Patients With High-Risk Stage III Melanoma
CTID: NCT03554083
Phase: Phase 2    Status: Active, not recruiting
Date: 2024-11-21
A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study
CTID: NCT03768063
Phase: Phase 3    Status: Recruiting
Date: 2024-11-20
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XL888 + Vemurafenib + Cobimetinib for Unresectable BRAF Mutated Stage III/IV Melanoma
CTID: NCT02721459
Phase: Phase 1    Status: Active, not recruiting
Date: 2024-11-20


A Study of Nivolumab Alone or Nivolumab Combination Therapy in Colon Cancer That Has Come Back or Has Spread
CTID: NCT02060188
Phase: Phase 2    Status: Completed
Date: 2024-11-19
A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer)
CTID: NCT03193190
Phase: Phase 1/Phase 2    Status: Active, not recruiting
Date: 2024-11-08
A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC)
CTID: NCT03178552
Phase: Phase 2/Phase 3    Status: Active, not recruiting
Date: 2024-11-01
Atezolizumab, Cobimetinib, and Eribulin in Treating Patients With Chemotherapy Resistant Metastatic Inflammatory Breast Cancer
CTID: NCT03202316
Phase: Phase 2    Status: Active, not recruiting
Date: 2024-10-29
Calaspargase Pegol-Mnkl and Cobimetinib for the Treatment of Locally Advanced or Metastatic Pancreatic Cancer
CTID: NCT05034627
Phase: Phase 1    Status: Recruiting
Date: 2024-10-28
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)
CTID: NCT03281369
Phase: Phase 1/Phase 2    Status: Active, not recruiting
Date: 2024-10-26
Testing the Combination of APG-1252 (Pelcitoclax) and Cobimetinib in Recurrent Ovarian and Endometrial Cancers
CTID: NCT05691504
Phase: Phase 1    Status: Recruiting
Date: 2024-10-09
A Study of Atezolizumab Plus Cobimetinib and Vemurafenib Versus Placebo Plus Cobimetinib and Vemurafenib in Previously Untreated BRAFv600 Mutation-Positive Patients With Metastatic or Unresectable Locally Advanced Melanoma
CTID: NCT02908672
Phase: Phase 3    Status: Completed
Date: 2024-10-01
A Study Evaluating the Efficacy and Safety of Biomarker-Driven Therapies in Patients With Persistent or Recurrent Rare Epithelial Ovarian Tumors
CTID: NCT04931342
Phase: Phase 2    Status: Active, not recruiting
Date: 2024-09-19
A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Small Cell Lung Cancer)
CTID: NCT03337698
Phase: Phase 1/Phase 2    Status: Active, not recruiting
Date: 2024-09-19
Cobimetinib in Extracranial Arteriovenous Malformations (COBI-AVM Study)
CTID: NCT05125471
Phase: Phase 2    Status: Recruiting
Date: 2024-09-03
Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders
CTID: NCT04079179
Phase: Phase 2    Status: Recruiting
Date: 2024-08-28
A MolEcularly Guided Anti-Cancer Drug Off-Label Trial
CTID: NCT04185831
Phase: Phase 2    Status: Active, not recruiting
Date: 2024-08-22
Targeted Pathway Inhibition in Patients With Pancreatic Cancer
CTID: NCT04005690
PhaseEarly Phase 1    Status: Recruiting
Date: 2024-08-19
Atezolizumab and Cobimetinib in Treating Patients With Metastatic, Recurrent, or Refractory Non-small Cell Lung Cancer
CTID: NCT03600701
Phase: Phase 2    Status: Active, not recruiting
Date: 2024-08-16
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.
CTID: NCT04835805
Phase: Phase 1    Status: Active, not recruiting
Date: 2024-08-14
Enasidenib in Combination With Cobimetinib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
CTID: NCT05441514
Phase: Phase 1    Status: Recruiting
Date: 2024-08-07
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
CTID: NCT02091141
Phase: Phase 2    Status: Completed
Date: 2024-07-23
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
CTID: NCT04941287
Phase: Phase 2    Status: Active, not recruiting
Date: 2024-07-19
LY3022855 With BRAF/MEK Inhibition in Patients With Melanoma
CTID: NCT03101254
Phase: Phase 1/Phase 2    Status: Completed
Date: 2024-07-17
The Finnish National Study to Facilitate Patient Access to Targeted Anti-cancer Drugs
CTID: NCT05159245
Phase: Phase 2    Status: Recruiting
Date: 2024-07-15
MEK Inhibitor and a PDL1 Inhibitor Patients With Locally Advanced and/or Metastatic Soft Tissue Sarcoma
CTID: NCT04216953
Phase: Phase 1/Phase 2    Status: Active, not recruiting
Date: 2024-07-08
Pre-operative Immunotherapy Combination Strategies in Breast Cancer
CTID: NCT03395899
Phase: Phase 2    Status: Completed
Date: 2024-06-18
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
CTID: NCT03498521
Phase: Phase 2    Status: Active, not recruiting
Date: 2024-06-14
Vemurafenib and Cobimetinib in Treating Patients With BRAF V600E Mutation Positive Craniopharyngioma
CTID: NCT03224767
Phase: Phase 2    Status: Active, not recruiting
Date: 2024-05-23
Evaluating the Efficacy and Safety of a Sequencing Schedule of Cobimetinib Plus Vemurafenib Followed by Immunotherapy With an Anti- PD-L1 Antibody in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma
CTID: NCT02902029
Phase: Phase 2    Status: Completed
Date: 2024-05-23
CRAFT: T
A MolEcularly Guided Anti-Cancer Drug Off-Label Trial
CTID: null
Phase: Phase 2    Status: Completed
Date: 2019-11-29
COTESARC - A multicentre Phase I-II study evaluating the combination of a MEK inhibitor and a PDL1 inhibitor in pediatric and adult patients with locally advanced and/or metastatic soft tissue sarcoma .
CTID: null
Phase: Phase 1, Phase 2    Status: Ongoing
Date: 2019-10-15
A PHASE II TWO COHORT STUDY EVALUATING
CTID: null
Phase: Phase 2    Status: Completed, Prematurely Ended
Date: 2018-08-30
A PHASE Ib/II, OPEN-LABEL, MULTICENTER, RANDOMIZED, UMBRELLA STUDY EVALUATING THE EFFICACY AND SAFETY OF MULTIPLE IMMUNOTHERAPY-BASED TREATMENT COMBINATIONS IN PATIENTS WITH LOCALLY ADVANCED UNRESECTABLE OR METASTATIC GASTRIC OR GASTROESOPHAGEAL JUNCTION CANCER OR ESOPHAGEAL CANCER(MORPHEUS-GASTRIC AND ESOPHAGEAL CANCER)
CTID: null
Phase: Phase 2    Status: GB - no longer in EU/EEA, Prematurely Ended
Date: 2018-07-17
A phase II, randomized, active-controlled, multi-center study comparing the efficacy and safety of targeted therapy or cancer immunotherapy guided by genomic profiling versus platinum-based chemotherapy in patients with cancer of unknown primary site who have recieved three cycles of platinum doublet chemotherapy
CTID: null
Phase: Phase 2    Status: Ongoing, Temporarily Halted, GB - no longer in EU/EEA, Prematurely Ended, Completed
Date: 2018-06-20
A PHASE IB/II STUDY OF COBIMETINIB ADMINISTERED AS SINGLE AGENT AND IN
CTID: null
Phase: Phase 2    Status: Completed
Date: 2018-03-19
A PHASE Ib/II, OPEN-LABEL, MULTICENTER, RANDOMIZED UMBRELLA STUDY EVALUATING THE EFFICACY AND SAFETY OF MULTIPLE IMMUNOTHERAPY-BASED TREATMENT COMBINATIONS IN PATIENTS WITH METASTATIC NONSMALL CELL LUNG CANCER (MORPHEUS-LUNG)
CTID: null
Phase: Phase 1, Phase 2    Status: Trial now transitioned, Ongoing, GB - no longer in EU/EEA
Date: 2018-01-25
A PHASE III, OPEN-LABEL, MULTICENTER, TWO ARM, RANDOMIZED STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF COBIMETINIB PLUS ATEZOLIZUMAB VERSUS PEMBROLIZUMAB IN PATIENTS WITH PREVIOUSLY UNTREATED ADVANCED BRAF V600 WILD-TYPE MELANOMA
CTID: null
Phase: Phase 3    Status: GB - no longer in EU/EEA, Prematurely Ended, Completed
Date: 2018-01-09
A PHASE II, OPEN-LABEL, MULTICENTER, MULTI-COHORT STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF COBIMETINIB PLUS ATEZOLIZUMAB IN PATIENTS WITH SOLID TUMORS
CTID: null
Phase: Phase 2    Status: Completed
Date: 2017-12-12
An evaluation of the efficacy beyond progression of vemurafenib combined with cobimetinib associated with local treatment compared to second-line treatment in patients with BRAFV600 mutation-positive metastatic melanoma in focal progression with first-line combined vemurafenib and cobimetinib.
CTID: null
Phase: Phase 2    Status: Completed
Date: 2017-11-23
An open-label phase II multicenter study of vemurafenib (Zelboraf®) plus cobimetinib (Cotellic®) after radiosurgery in patients with active BRAF-V600-mutant melanoma brain metastases
CTID: null
Phase: Phase 2    Status: Restarted
Date: 2017-11-21
A phase II study investigating preoperative combination strategies for immunotherapy in patients with untreated, operable ER+, HER2-negative primary breast cancer.
CTID: null
Phase: Phase 2    Status: GB - no longer in EU/EEA, Prematurely Ended
Date: 2017-11-16
A phase II trial of vemurafenib plus cobimetinib in patients treated with prior first-line systemic immunotherapy for inoperable locally advanced or metastatic melanoma
CTID: null
Phase: Phase 2    Status: Prematurely Ended
Date: 2017-10-09
STEP-WISE COMBINATION OF OBINUTUZUMAB, VEMURAFENIB AND COBIMETINIB IN PATIENTS WITH HAIRY CELL LEUKEMIA (HCL) PREVIOUSLY TREATED WITH PURINE ANALOGS OR UNFIT FOR CHEMOTHERAPY: A PHASE-2, SINGLE-ARMS, ITALIAN, MULTICENTER STUDY (HCL-PG04)
CTID: null
Phase: Phase 2    Status: Ongoing
Date: 2017-09-19
A PHASE I/II, MULTICENTER, OPEN-LABEL, DOSE-ESCALATION STUDY OF THE SAFETY AND PHARMACOKINETICS OF COBIMETINIB IN PEDIATRIC AND YOUNG ADULT PATIENTS WITH PREVIOUSLY TREATED SOLID TUMORS
CTID: null
Phase: Phase 1, Phase 2    Status: GB - no longer in EU/EEA, Completed
Date: 2016-10-07
A PHASE III, DOUBLE-BLINDED, RANDOMIZED, PLACEBO-CONTROLLED STUDY OF
CTID: null
Phase: Phase 3    Status: Ongoing, GB - no longer in EU/EEA, Completed
Date: 2016-10-06
A Phase III, open-label, multicenter, three-arm, randomized study to investigate the efficacy and safety of cobimetinib plus atezolizumab and atezolizumab monotherapy vs. regorafenib in patients with previously treated unresectable locally advanced or metastatic colorectal adenocarcinoma
CTID: null
Phase: Phase 3    Status: Prematurely Ended, Completed
Date: 2016-08-18
A phase II, multicenter, open-label, randomized-controlled trial evaluating the efficacy and safety of a sequencing schedule of cobimetinib plus vemurafenib followed by immunotherapy with an anti- PD-L1 antibody atezolizumab for the treatment in patients with unresectable or metastatic BRAF V600 mutant melanoma
CTID: null
Phase: Phase 2    Status: Ongoing, Completed
Date: 2016-07-05
A phase Ib/II multi-arm study with venetoclax in combination with cobimetinib, and venetoclax in combination with idasanutlin in patients ≥ 60 years with relapsed or refractory acute myeloid leukemia who are not eligible for cytotoxic therapy
CTID: null
Phase: Phase 1, Phase 2    Status: Prematurely Ended
Date: 2016-05-11
A SINGLE ARM, OPEN LABEL, PHASE II, MULTICENTER STUDY TO ASSESS THE DETECTION OF THE BRAF V600 MUTATION ON cfDNA FROM PLASMA IN PATIENTS WITH ADVANCED MELANOMA
CTID: null
Phase: Phase 2    Status: Completed
Date: 2016-03-09
Evaluation of cobimetinib + vemurafenib combination treatment in patients with brain metastasis BRAFV600 mutated cutaneous melanoma
CTID: null
Phase: Phase 2    Status: Completed
Date: 2015-07-31
A randomized Phase II study of vemurafenib plus cobimetinib continuous versus intermittent, in previously untreated BRAFV600- mutation positive patients with unresectable locally advanced or metastatic melanoma.
CTID: null
Phase: Phase 2    Status: Completed
Date: 2015-02-19
A Phase II, Open-Label, Multicenter Study of Vemurafenib plus Cobimetinib (GDC-0973) in Unresectable Stage IIIc or Metastatic Melanoma; Response Monitoring and Resistance Prediction with Positron Emission Tomography and Tumor Characteristics.
CTID: null
Phase: Phase 2    Status: Ongoing
Date: 2014-10-15
Neoadjuvant treatment with the combination of Vemurafenib, Cobimetinib and Atezolizumab in limited metastasis of malignant melanoma (AJCC stage IIIC/IV) and integrated biomarker study: A single armed, two-cohort, phase II EADO trial NEO-VC
CTID: null
Phase: Phase 2    Status: Prematurely Ended
Date: 2014-10-02
A PHASE III, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF VEMURAFENIB VERSUS VEMURAFENIB
CTID: null
Phase: Phase 3    Status: Completed
Date: 2013-02-06

Biological Data
  • Cobimetinib (GDC-0973, RG7420)

    FDG-PET imaging. FDG-PET imaging is effective for monitoring vemurafenib and GDC-0973 combination drug action in BRAFV600E mutant and resistant xenografts. EJNMMI Res. 2012; 2: 22.

  • Cobimetinib (GDC-0973, RG7420)

    GDC-0973 is a selective, potent MEK inhibitor with efficacy in BRAF and RAS mutant cell lines. A, chemical structure of GDC-0973. B, GDC-0973 was tested in a panel of cell lines in 96-hour viability assays.2012 Jan 1;72(1):210-9.

  • Cobimetinib (GDC-0973, RG7420)

    GDC-0973 single-agent efficacy and pharmacodynamic (PD) studies in BRAFV600Eand KRAS mutant tumor models. Dose-ranging efficacy studies were carried out in the (A) A375.X1 and (B) NCI-H2122 tumor xenograft models.2012 Jan 1;72(1):210-9.

  • Cobimetinib (GDC-0973, RG7420)

    Combination of GDC-0973 + GDC-0941 results in reduced viability, pathway inhibition, and increased apoptosis. A, the 888MEL and A2058 BRAF mutant melanoma cell lines were treated with increasing concentrations of GDC-0973 and GDC-0941 as single agents and in combination and assayed in a 96-hour viability assay.2012 Jan 1;72(1):210-9.

  • Cobimetinib (GDC-0973, RG7420)

    GDC-0973 and GDC-0941 combination results in TGI when dosed daily.2012 Jan 1;72(1):210-9.

  • Cobimetinib (GDC-0973, RG7420)

    GDC-0973 and GDC-0941 combination results in TGI when dosed intermittently.


    Cobimetinib (GDC-0973, RG7420)

    Transient treatment of GDC-0973 + GDC-0941 results in apoptosis and prolonged accumulation of Bim.

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