Cobimetinib
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | DRUG-COBIMETINIB |
|---|---|
| Type | Drug |
| Aliases | CotellicGDC-0973XL518Кобіметиніб |
| Status | reviewed 2026-04-27 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-ESMO-MELANOMA-2024 SRC-NCCN-MELANOMA-2025 |
Drug Facts
| Class | MEK1/2 inhibitor |
|---|---|
| Mechanism | Reversible selective allosteric inhibitor of MEK1 and MEK2, binding adjacent to the ATP site and preventing phosphorylation/activation of ERK1/2 in the RAS-RAF-MEK-ERK signaling cascade. Used in combination with vemurafenib (BRAFi) for BRAF V600 unresectable / metastatic melanoma to suppress paradoxical MAPK pathway reactivation seen with BRAFi monotherapy (coBRIM, mPFS 12.3 vs 7.2 mo for vemurafenib alone; mOS 22.3 vs 17.4 mo). Also part of the IMspire150 triplet (atezolizumab + cobimetinib + vemurafenib) for previously untreated BRAF V600 advanced melanoma, where the addition of atezolizumab modestly extended PFS. Off-label in NF1 plexiform neurofibroma and RAS-mutant histiocytic neoplasms. |
| Typical dosing | 60 mg PO once daily on a 21-days-on / 7-days-off schedule (28-day cycle), in combination with vemurafenib 960 mg PO BID continuous (coBRIM regimen). For IMspire150 triplet: 28-day lead-in of vemurafenib + cobimetinib only, then add atezolizumab cycle 2 onward. Dose modifications: -1 = 40 mg daily; -2 = 20 mg daily; permanent discontinuation if persistent G3-4 cardiac, ocular, or hepatic toxicity. No specific renal adjustment. Avoid in severe hepatic impairment. |
| Ukraine registered | False |
| NSZU reimbursed | False |
| Ukraine last verified | 2026-04-27 |
Notes
Sun-protective measures (SPF 50+, protective clothing, hat) are critical because vemurafenib already causes severe photosensitivity and the combination amplifies it. Mandatory baseline + serial monitoring: LFTs (q2wk x first 8 wk then monthly), CK + creatinine if CK rises, LVEF echo at baseline / 1 mo / q3mo, ophthalmologic exam (OCT) at baseline + for any new visual symptom, dermatologic exam q2-3 mo (BRAFi + MEKi class — cutaneous SCC + new primary melanoma surveillance). In contemporary practice dabrafenib+trametinib is preferred where both are available (similar efficacy, less photosensitivity, more pyrexia trade-off). Triplet (IMspire150) reserved for high-risk patients where atezolizumab access is reimbursed.
Used By
No reverse references found in the YAML corpus.