ArticleInvestigational new drugs2016
A first-in-human phase I study to evaluate the MEK1/2 inhibitor, cobimetinib, administered daily in patients with advanced solid tumors.
Article in Investigational new drugs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Predictability of human exposure by human-CYP3A4-transgenic mouse models: A meta-analysis.Clinical and translational science · 2024Pooled it
- Systematic review of combinations of targeted or immunotherapy in advanced solid tumors.Journal for immunotherapy of cancer · 2021Pooled it
- Safety and efficacy of cobimetinib plus atezolizumab in patients with solid tumors: a phase II, open-label, multicenter, multicohort study.ESMO open · 2023Trial
- Differential Outcomes in Codon 12/13 and Codon 61Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Randomised phase II trial (SWOG S1310) of single agent MEK inhibitor trametinib Versus 5-fluorouracil or capecitabine in refractory advanced biliary cancer.European journal of cancer (Oxford, England : 1990) · 2020Trial
- Trial
- Targeted therapy in BRAF‑mutant melanoma: Advances and challenges (Review).International journal of oncology · 2026Review
- Tempered signal strength via low-dose MEK inhibition optimizes therapeutic performance of engineered T cells.Journal for immunotherapy of cancer · 2025Article
- Review
- Targeting KRAS in colorectal cancer (Review).Molecular and clinical oncology · 2025Review
- Emerging strategies in colorectal cancer immunotherapy: enhancing efficacy and survival.Frontiers in immunology · 2025Review
- Mucocutaneous toxicities from MEK inhibitors: a scoping review of the literature.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024Article
- Effect of Mifepristone on Migration and Proliferation of Oral Cancer Cells.International journal of molecular sciences · 2024Article
- Article
- Nivolumab monotherapy or combination with ipilimumab with or without cobimetinib in previously treated patients with pancreatic adenocarcinoma (CheckMate 032).Journal for immunotherapy of cancer · 2024Article
- Vaccine antibodies against a synthetic epidermal growth factor variant enhance the antitumor effects of inhibitors targeting the MAPK/ERK and PI3K/Akt pathways.Translational oncology · 2024Article
- CASPER: A Phase I trial combining calaspargase pegol-mnkl and cobimetinib in pancreatic cancer.Future oncology (London, England) · 2024Article
- Exploring the Therapeutic Potential ofCurrent drug discovery technologies · 2024Article
- Precision medicine in nasopharyngeal carcinoma: comprehensive review of past, present, and future prospect.Journal of translational medicine · 2023Review
- MEK inhibitors in cancer treatment: structural insights, regulation, recent advances and future perspectives.RSC medicinal chemistry · 2023Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Objective Cobimetinib, a MEK1/2 inhibitor, was administered to patients with advanced solid tumors to assess safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity. Methods For dose-escalation, a 3 + 3 design was used. Oral cobimetinib was administered once daily on a 21-day on/7-day off (21/7) or a 14-day on/14-day off (14/14) schedule. Serial plasma samples were collected for pharmacokinetic (PK) analysis on Day 1 and at steady state. In expansion stages, patients with RAS or RAF mutant tumors were treated at the maximum tolerated dose (MTD) of the 21/7 or 14/14 schedule. Results Ninety-seven patients received cobimetinib. In the 21/7 dose escalation, 36 patients enrolled in 8 cohorts (0.05 mg/kg-80 mg). Dose-limiting toxicities (DLTs) were Grade 4 hepatic encephalopathy, Grade 3 diarrhea, and Grade 3 rash. In the 14/14 dose escalation, 20 patients enrolled in 4 cohorts (60-125 mg). DLTs were Grade 3 rash and Grade 3 blurred vision associated with presence of reversible subretinal fluid. The MTD was 60 mg on 21/7 schedule and 100 mg on 14/14 schedule. Cobimetinib PK showed dose-proportional increases in exposure. The most frequent adverse events attributed to cobimetinib were diarrhea, rash, fatigue, edema, nausea, and vomiting. In patients treated at the 60-mg (21/7) or 100-mg (14/14) dose, one unconfirmed complete response and 6 confirmed partial responses were observed. All responses occurred in melanoma patients; 6 harbored the BRAF(V600E) mutation. Conclusions Cobimetinib is generally well tolerated and durable responses were observed in BRAF(V600E) mutant melanoma patients. Evaluation of cobimetinib in combination with other therapies is ongoing.
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