Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Pimasertib · 2 trials · 2 indications
PFS was defined as the duration (in weeks) from randomization until the first progressive disease (PD) observation as assessed by the Investigator according to Response Evaluation Criteria for Solid Tumors (RECIST) version 1.1, or death due to any cause when death occurred within 12 weeks after the last tumor assessment (otherwise censored), whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters of the target lesions, taking as reference the smallest sum since the treatment started (including baseline), or appearance of one or more new lesions, and/or unequivocal progression of existing non-target lesions.
Oral bioavailability (F) was calculated using the formula=AUC0-inf oral/dose oral) / (AUC0-inf iv/dose iv) \* 100%, where AUC0-inf is the area under the concentration time curve (AUC) from time zero to infinity.
Recovery of total \[14C\]-radioactivity was determined in excreta, i.e., urine and feces at each sampling period subsequent to oral administration of \[14C\]-pimasertib on Day 8. Cumulative recovery of total \[14C\]-radioactivity in terms of percentage of dose recovered in urine and feces and total percentage of dose recovered was reported for the outcome measure.
Plasma concentration of the Pimasertib metabolite M445 and M554 were presented for the outcome measure.
Identification and profiling of the metabolites was done. The total number of metabolites and the number of metabolites identified as major were reported.
| Arm | Type | Description |
|---|---|---|
| Pimasertib | EXPERIMENTAL | - |
| Dacarbazine | ACTIVE_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| Pimasertib | DRUG | Subjects will receive pimasertib orally as monotherapy at a dose of 60 milligram (mg) twice daily continuously. Treatment will consist of repeated 21-day cycles which will continue until progression of the disease, unacceptable toxicity, withdrawal of informed consent, or death, whichever occurs first. |
| Dacarbazine | DRUG | Subjects will receive dacarbazine intravenously at dose of 1000 milligram per square meter (mg/m\^2) of body surface area every 3 weeks on Day 1 of each 21-days cycle until progression of the disease, unacceptable toxicity, withdrawal of informed consent, or death, whichever occurs first. Eligible subjects with documented tumor progression on dacarbazine will offer to switch to pimasertib treatment. |
Inclusion Criteria: * Subjects with measurable, histologically or cytologically confirmed, locally advanced or metastatic cutaneous melanoma (stage III c or M1ac) N-Ras mutated. If N-Ras mutational status is unknown at screening, it must be prospectively defined before inclusion. If N-Ras mutationa...
Pimasertib is an investigational small molecule being studied for the treatment of N-Ras mutated locally advanced or metastatic malignant cutaneous melanoma, as well as locally advanced or metastatic solid tumors. It is in clinical development and is not approved by the FDA.
Pimasertib is a small molecule that targets the MEK pathway, which is involved in cell growth and proliferation. It is being studied in cancers with N-Ras mutations, where this pathway is often overactive.
Pimasertib is being developed by Merck & Company, Inc., which is publicly traded under the ticker symbol MRK on the New York Stock Exchange.
Pimasertib is in Phase 1 clinical development. It has completed a Phase 2 trial in N-Ras mutated cutaneous melanoma and a Phase 1 trial in solid tumors, but it remains investigational and has not been approved.
Pimasertib has been studied in two completed clinical trials. NCT01693068 was a Phase 2 trial in N-Ras mutated cutaneous melanoma with 194 participants, and NCT01713036 was a Phase 1 trial in solid tumors with 6 participants.
Pimasertib is a specific MEK inhibitor developed by Merck & Company. It is not the same as other MEK inhibitors, which are distinct compounds with their own chemical structures and development programs.