Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as OKI-179
OKI-179+ binimetinib · 2 trials · 4 indications
Incidence and severity of DLTs will be measured in the DLT-evaluable population during Cycle 1.
AEs will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Changes from baseline through study treatment will be analyzed using NCI CTCAE version 5.0 grade criteria
Objective responses will be determined per RECIST version 1.1 criteria, and the ORR will be defined as the proportion of patients with the best overall confirmed response of complete response (CR) or partial response (PR) in the Efficacy-Evaluable Population
Tolerability
* Incidence and severity of adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5 * Incidence and severity of Serious Adverse Events * Incidence and severity of dose-limiting toxicities (DLTs) * Findings of changes in clinical laboratory abnormalities * Changes in triplicate 12-lead electrocardiogram (ECG) parameters * Changes in the Eastern Cooperative Oncology Group (ECOG) performance status (PS) * Changes in physical examination findings
| Arm | Type | Description |
|---|---|---|
| OKI-179 + binimetinib | EXPERIMENTAL | - |
| Experimental: Phase 1 - Dose Escalation | EXPERIMENTAL | Dose escalation trial evaluating OKI-179 given orally on a daily basis. Patients will take OKI-179 orally (PO) on Days 1 - 4, 8 - 11 and 15 - 18 in 21-day cycles (± 3 days), under fasted conditions. The design is a modified 3+3 design to determine the maximum tolerated dose and allows for additional cohorts enrolling subjects with an alternative dosing schedule such as OKI-179 orally (PO) daily on Days 1 - 5, 8 - 12 and 15 - 19 per 21-day cycles or Days 1 - 21 per 21-day cycles to determine the maximum tolerated dose for continuous daily dosing. |
| Name | Type | Description |
|---|---|---|
| OKI-179 + binimetinib | DRUG | Phase 1b: With a 3+3 dose escalation design, enrollment in Phase 1b will proceed until the MTD has been defined or the highest dose level has been reached. OKI-179 will be administered on a 4-days-on/3-days-off schedule, while binimetinib will be administered BID continuously. Phase 2: Patients will be treated with the RP2D. |
| OKI-179 | DRUG | OKI-179 single agent |
Inclusion Criteria: * Phase 1b: Solid tumor refractory to standard treatment, for which no standard therapy is available, or if the patient refuses standard therapy * Phase 1b: Tumor has an activating mutation in the RAS pathway confirmed by any local or central laboratory, including but not limite...
| 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 |
OKI-179 is an investigational small molecule drug being developed by OnKure Therapeutics, Inc. for advanced solid tumors, including tumors with RAS mutations. It is a Class I HDAC inhibitor studied in Phase 1 clinical development, both as a single agent and in combination with binimetinib.
OKI-179 targets HDAC, specifically the Class I histone deacetylase enzymes. It is classified as a Class I HDAC inhibitor, a small molecule designed to inhibit these enzymes in tumor cells. OnKure Therapeutics is developing it for advanced solid tumors, including RAS-mutated disease.
OKI-179 is being developed by OnKure Therapeutics, Inc., which trades under the ticker OKUR. The company has studied the drug in Phase 1 trials in advanced solid tumors, including a combination study with binimetinib in RAS pathway tumors and NRAS-mutated melanoma.
OKI-179 is in Phase 1 development. It is investigational and has been evaluated in completed Phase 1 studies, including a Phase 1b portion of the NAUTILUS trial testing OKI-179 plus binimetinib in advanced solid tumors with RAS pathway alterations.
OKI-179 has been studied in two completed Phase 1 trials. NCT05340621, the NAUTILUS trial, tested OKI-179 plus binimetinib in RAS pathway advanced solid tumors and NRAS-mutated melanoma with 36 patients enrolled. NCT03931681 studied OKI-179 in advanced solid tumors with 34 patients enrolled. Both were conducted in the United States.