Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
KPT-9274 · 1 trial · 3 indications
Dose escalation will continue until the MTD is determined. The MTD is defined as the highest dose at which ≤1 patient experiences a DLT in Cycle 1. Count of participants who did not experience a DLT are listed in outcome measure data table.
| Arm | Type | Description |
|---|---|---|
| De-escalation Cohort; 20mg | ACTIVE_COMPARATOR | For the purposes of dose escalation decisions, a standard 3+3 dose escalation design will be used.The initial cohort, Cohort 1, will consist of 3 enrolled patients who will be treated at 30 mg. If the MTD is exceeded at cohort 1, de-escalation to cohort 0 (20 mg) will occur. If the MTD is not exceeded in cohort 1, dose escalation will continue based on a standard 3+3 design at the dose levels. |
| Cohort 1; 30 mg | ACTIVE_COMPARATOR | The initial cohort, Cohort 1, will consist of 3 enrolled patients who will be treated at 30 mg. |
| Cohort 2; 40mg | ACTIVE_COMPARATOR | Dose escalation to 40 mg after initial cohort (Cohort 1) after a minimum of 1 cycle of treatment, defined as receiving ≥75% of KPT-9274 doses during Cycle 1 (e.g., ≥9 of 12 doses in the 3 doses/week schedule), or have a DLT within the first cycle of treatment to be evaluable for dose escalation decisions. |
| Cohort 3; 60mg | ACTIVE_COMPARATOR | Dose escalation to 60 mg after initial cohort (Cohort 1) after a minimum of 1 cycle of treatment, defined as receiving ≥75% of KPT-9274 doses during Cycle 1 (e.g., ≥9 of 12 doses in the 3 doses/week schedule), or have a DLT within the first cycle of treatment to be evaluable for dose escalation decisions. |
| Cohort 4; 80mg | ACTIVE_COMPARATOR | Dose escalation to 80 mg after initial cohort (Cohort 1) after a minimum of 1 cycle of treatment, defined as receiving ≥75% of KPT-9274 doses during Cycle 1 (e.g., ≥9 of 12 doses in the 3 doses/week schedule), or have a DLT within the first cycle of treatment to be evaluable for dose escalation decisions. |
| Cohort 5; 100mg | ACTIVE_COMPARATOR | Dose escalation to 100 mg after initial cohort (Cohort 1) after a minimum of 1 cycle of treatment, defined as receiving ≥75% of KPT-9274 doses during Cycle 1 (e.g., ≥9 of 12 doses in the 3 doses/week schedule), or have a DLT within the first cycle of treatment to be evaluable for dose escalation decisions. |
| Name | Type | Description |
|---|---|---|
| KPT-9274 | DRUG | KPT-9274 is a first-in-class orally bioavailable, non-competitive, small molecule, dual modulator of p21 protein (Cdc42/Rac)-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase /PBEF/visfatin (NAMPT). NAMPT is the rate-limiting enzyme in the metabolic scavenging pathway that utilizes nicotinamide to replenish nicotinamide adenine dinucleotide (NAD), an essential metabolic cofactor and second messenger. Recent investigations have shown that in in vitro and in vivo models, NAMPT is uniquely essential for relapsed or refractory AML stem cells. Targeting relapsed AML stem cells, through targeting of NAMPT, may allow for a promising therapeutic opportunity for patients with relapsed or refractory AML. |
Inclusion Criteria: 1. Written informed consent obtained prior to any study related procedures required solely for this research study. 2. Age ≥18 years. 3. Patients with WHO-confirmed non-APL AML who have not responded to or relapsed after at least one prior therapy and for whom no standard therap...
KPT-9274 is an investigational small molecule being studied for the treatment of acute myeloid leukemia (AML), specifically in patients with relapsed or refractory disease. It is being developed by Karyopharm Therapeutics Inc. and has been evaluated in a Phase 1 clinical trial. It is not approved for any indication.
KPT-9274 targets two proteins: PAK4 and NAMPT. PAK4 is a serine/threonine kinase involved in cell signaling, and NAMPT is an enzyme in the NAD salvage pathway. By inhibiting both targets, KPT-9274 is designed to interfere with pathways that support cancer cell survival and proliferation.
KPT-9274 is being developed by Karyopharm Therapeutics Inc., a biopharmaceutical company traded on the Nasdaq under the ticker symbol KPTI. Karyopharm is focused on the discovery and development of novel therapies for cancer and other diseases.
KPT-9274 is in Phase 1 clinical development. It has completed a Phase 1 trial in patients with relapsed and refractory acute myeloid leukemia. As an investigational drug, it has not been approved by the FDA for any indication.
KPT-9274 has been studied in one completed Phase 1 clinical trial, NCT04914845, titled "KPT-9274 in Patients With Relapsed and Refractory Acute Myeloid Leukemia." The trial enrolled 16 patients in the United States and was active-controlled. No other trials are listed.