Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
MK-8353 · 1 trial · 1 indication
A dose limiting toxicity (DLT) is defined as any hematologic or non-hematologic toxicity ≥Grade 3 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. The occurrence of any of the designated toxicities during Cycle 1 (3-week cycle) were considered a DLT, if assessed by the investigator to be possibly, probably, or definitely related to study treatment administration. The number of participants experiencing DLTs was assessed.
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants experiencing AEs was assessed.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants discontinuing study treatment due to AEs was assessed.
| Arm | Type | Description |
|---|---|---|
| MK-8353 and Selumetinib Dose Escalation | EXPERIMENTAL | Participants will receive a combination MK-8353 and selumetinib for 4 days on and 3 days off until disease progression or discontinuation. MK-8353 will be escalated sequentially from 50 mg to 250 mg based on pharmacokinetic and safety data. Selumetinib will be escalated sequentially from 25 mg to 75 mg based on pharmacokinetic and safety data. Doses may be adjusted downward sequentially based on tolerability |
| Name | Type | Description |
|---|---|---|
| MK-8353 | DRUG | Participants will receive MK-8353 orally twice daily (BID), escalated sequentially from 50 mg to 250 mg. |
| Selumetinib | DRUG | Participants will receive selumetinib orally BID, escalated sequentially from 25 mg to 75 mg. |
Inclusion Criteria: * Have a histologically- or cytologically-documented, locally-advanced or metastatic solid tumor by pathology report and have received, or been intolerant to, all treatment known to confer clinical benefit. * Provide an archival or newly obtained tumor tissue sample and blood sa...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Merck & Co., Inc. | MRK | 3 | PHASE2 | Pembrolizumab, Gardasil 9 |
| Incyte Corporation | INCY | 1 | PHASE2 | Retifanlimab |
| Novartis AG Sponsored ADR | NVS | 1 | PHASE1 | KFA115 |
| Iovance Biotherapeutics Inc | IOVA | 2 | PHASE2 | Aldesleukin |
| AstraZeneca PLC | AZN | 1 | - | Trastuzumab deruxtecan |
MK-8353 is an investigational small molecule being studied for the treatment of advanced and metastatic solid tumors. It has been evaluated in a Phase 1 clinical trial in adult patients with solid tumors, including testing in combination with selumetinib. It is not an approved therapy.
MK-8353 targets MAPK3 and MAPK1, also known as ERK1 and ERK2, two kinases in the MAPK signaling pathway. It acts as an inhibitor of these targets. Because the MAPK pathway is frequently dysregulated in cancer, inhibiting MAPK1 and MAPK3 is intended to interfere with tumor cell signaling.
MK-8353 is being developed by Merck & Company, Inc., which trades on the New York Stock Exchange under the ticker MRK. Merck is the sponsor of the clinical program evaluating the compound in solid tumors.
MK-8353 is in Phase 1 clinical development. It is an investigational agent and has not been approved by the FDA for any indication. The Phase 1 program in solid tumors has been completed, and no trials of MK-8353 are currently listed as active.
MK-8353 has been studied in one Phase 1 trial, NCT03745989, titled Study of MK-8353 + Selumetinib in Advanced/Metastatic Solid Tumors (MK-8353-014). That trial enrolled 30 adults with solid tumors across the United States, Canada, and Switzerland, and its status is completed.
NCT03745989 was a Phase 1, uncontrolled, open-label study that enrolled 30 adult patients with advanced or metastatic solid tumors. It was not randomized and not double blinded, and participants were not selected by a biomarker. The trial evaluated MK-8353 given in combination with selumetinib.