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| Title |
A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor
|
|---|---|
| Published in |
British Journal of Cancer, February 2017
|
| DOI | 10.1038/bjc.2017.10 |
| Pubmed ID | |
| Authors |
Johanna C Bendell, Milind Javle, Tanios S Bekaii-Saab, Richard S Finn, Zev A Wainberg, Daniel A Laheru, Colin D Weekes, Benjamin R Tan, Gazala N Khan, Mark M Zalupski, Jeffrey R Infante, Suzanne Jones, Kyriakos P Papadopoulos, Anthony W Tolcher, Renae E Chavira, Janna L Christy-Bittel, Emma Barrett, Amita Patnaik |
| Abstract |
Binimetinib (MEK162; ARRY-438162) is a potent and selective oral MEK 1/2 inhibitor. This phase 1 study determined the maximum tolerated dose (MTD), safety, pharmacokinetic and pharmacodynamic profiles, and preliminary anti-tumour activity of binimetinib in patients with advanced solid tumours, with expansion cohorts of patients with biliary cancer or KRAS- or BRAF-mutant colorectal cancer. Binimetinib was administered twice daily. Expansion cohorts were enroled after MTD determination following a 3+3 dose-escalation design. Pharmacokinetic properties were determined from plasma samples. Tumour samples were assessed for mutations in RAS, RAF, and other relevant genes. Pharmacodynamic properties were evaluated in serum and skin punch biopsy samples. Ninety-three patients received binimetinib (dose-escalation phase, 19; expansion, 74). The MTD was 60 mg twice daily, with dose-limiting adverse events (AEs) of dermatitis acneiform and chorioretinopathy. The dose for expansion patients was subsequently decreased to 45 mg twice daily because of the frequency of treatment-related ocular toxicity at the MTD. Common AEs across all dose levels included rash (81%), nausea (56%), vomiting (52%), diarrhoea (51%), peripheral oedema (46%), and fatigue (43%); most were grade 1/2. Dose-proportional increases in binimetinib exposure were observed and target inhibition was demonstrated in serum and skin punch biopsy samples. Three patients with biliary cancer had objective responses (one complete and two partial). Binimetinib demonstrated a manageable safety profile, target inhibition, and dose-proportional exposure. The 45 mg twice daily dose was identified as the recommended phase 2 dose. The three objective responses in biliary cancer patients are encouraging and support further evaluation in this population.British Journal of Cancer advance online publication, 2 February 2017; doi:10.1038/bjc.2017.10 www.bjcancer.com. |
X Demographics
The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 20% |
| Unknown | 4 | 80% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 60% |
| Science communicators (journalists, bloggers, editors) | 1 | 20% |
| Practitioners (doctors, other healthcare professionals) | 1 | 20% |
Mendeley readers
The data shown below were compiled from readership statistics for 99 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 99 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 14 | 14% |
| Student > Bachelor | 11 | 11% |
| Student > Ph. D. Student | 10 | 10% |
| Other | 9 | 9% |
| Student > Master | 9 | 9% |
| Other | 14 | 14% |
| Unknown | 32 | 32% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 19 | 19% |
| Biochemistry, Genetics and Molecular Biology | 14 | 14% |
| Pharmacology, Toxicology and Pharmaceutical Science | 12 | 12% |
| Nursing and Health Professions | 5 | 5% |
| Agricultural and Biological Sciences | 5 | 5% |
| Other | 9 | 9% |
| Unknown | 35 | 35% |
Attention Score in Context
This research output has an Altmetric Attention Score of 13. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 November 2022.
All research outputs
#2,361,726
of 22,774,233 outputs
Outputs from British Journal of Cancer
#1,335
of 10,415 outputs
Outputs of similar age
#52,614
of 419,220 outputs
Outputs of similar age from British Journal of Cancer
#39
of 98 outputs
Altmetric has tracked 22,774,233 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 10,415 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.6. This one has done well, scoring higher than 87% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 419,220 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 87% of its contemporaries.
We're also able to compare this research output to 98 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 60% of its contemporaries.