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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 acute myeloid leukemia, including relapsed and refractory forms of the disease. It was evaluated in a Phase 1 trial in adult patients with relapsed and refractory AML. It is not an approved therapy and remains in clinical development.
KPT-9274 targets two proteins: PAK4 and NAMPT. Both are molecular targets of the small molecule, which places it among dual-target agents in oncology research. Its clinical evaluation focused on acute myeloid leukemia, where the drug was tested in a Phase 1 study.
KPT-9274 is being developed by Karyopharm Therapeutics Inc., which trades under the ticker KPTIQ. The company sponsored the Phase 1 study of the drug in relapsed and refractory acute myeloid leukemia conducted in the United States.
KPT-9274 is in Phase 1 development. Its single clinical trial, a Phase 1 study in relapsed and refractory acute myeloid leukemia, has been completed. The drug is investigational and is not an approved treatment for AML or any other indication.
KPT-9274 has been studied in one clinical trial, NCT04914845, titled KPT-9274 in Patients With Relapsed and Refractory Acute Myeloid Leukemia. The Phase 1 trial enrolled 16 adults aged 18 and older in the United States and is completed. It was active-controlled and not randomized or double-blind.