KOMET-001
First in human study of ziftomenib in relapsed or refractory acute myeloid leukemia (KOMET-001)
Phase 1/2NCT04067336
- Population
- Relapsed or refractory AML (phase 1: all molecular subtypes in escalation; NPM1-mutated or KMT2A-rearranged in expansion; phase 2: NPM1-mutated)
- Design
- Multicentre, open-label, multi-cohort phase 1/2 trial of oral ziftomenib. Phase 1 (dose escalation, dose validation and expansion) reported in Lancet Oncology; the registration-enabling phase 2 part (ziftomenib 600 mg once daily in relapsed or refractory NPM1-mutated AML) reported in the Journal of Clinical Oncology. Single-arm in phase 2; no randomized comparator in the cohorts reported here.
- Arms
- Ziftomenib (experimental): Ziftomenib orally once daily (phase 2: 600 mg)
- People
- Wang ES
Show the numbers
| Endpoint | Analysis | Ziftomenib | Control | Effect |
|---|---|---|---|---|
| CR+CRhPhase 1b patients with KMT2A rearrangement or NPM1 mutation treated at 600 mg (n = 36)Complete remission or complete remission with partial haematologic recovery | primaryWang 2024 | 25% | — | No responses were reported at the 200 mg dose level. 7 (35%) of 20 patients with an NPM1 mutation at the recommended phase 2 dose had a complete remission. |
| CR+CRhTreated patients with relapsed or refractory NPM1-mutated AML (n = 92)Complete remission with full hematologic recovery or complete remission with partial hematologic recovery | primaryWang 2025 | 22% (14–32%) | — | P=.0058The abstract states the primary end point was met. The P value tests against a 12% historical standard-of-care response rate (full text), not a concurrent control. 61% were reported negative for measurable residual disease (among responders with samples evaluable by the central laboratory; denominator not given in the abstract). |
| ORRTreated patients with relapsed or refractory NPM1-mutated AML (n = 92)Overall response rate in relapsed or refractory AML; response criteria are not given in the abstract | primaryWang 2025 | 33% (23–43%) | — | Median duration of response 4.6 months (95% CI 2.8 to 7.4), as stated in the abstract. Secondary end point. |
| OSTreated patients with relapsed or refractory NPM1-mutated AML (n = 92) | primaryWang 2025 | median 6.6 months (3.6–8.6) | — | Single-arm; there is no comparator for this median. |
| Endpoint | Analysis | Ziftomenib | Control | Effect |
|---|---|---|---|---|
| CR+CRhPhase 1b patients with KMT2A rearrangement or NPM1 mutation treated at 600 mg (n = 36)Complete remission or complete remission with partial haematologic recovery | primaryWang 2024 | 25% | — | No responses were reported at the 200 mg dose level. 7 (35%) of 20 patients with an NPM1 mutation at the recommended phase 2 dose had a complete remission. |
| CR+CRhTreated patients with relapsed or refractory NPM1-mutated AML (n = 92)Complete remission with full hematologic recovery or complete remission with partial hematologic recovery | primaryWang 2025 | 22% (14–32%) | — | P=.0058The abstract states the primary end point was met. The P value tests against a 12% historical standard-of-care response rate (full text), not a concurrent control. 61% were reported negative for measurable residual disease (among responders with samples evaluable by the central laboratory; denominator not given in the abstract). |
| ORRTreated patients with relapsed or refractory NPM1-mutated AML (n = 92)Overall response rate in relapsed or refractory AML; response criteria are not given in the abstract | primaryWang 2025 | 33% (23–43%) | — | Median duration of response 4.6 months (95% CI 2.8 to 7.4), as stated in the abstract. Secondary end point. |
| OSTreated patients with relapsed or refractory NPM1-mutated AML (n = 92) | primaryWang 2025 | median 6.6 months (3.6–8.6) | — | Single-arm; there is no comparator for this median. |
- Ziftomenib (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Ziftomenib |
|---|---|
| 0 | 100.0% |
| 4 | 65.7% |
| 8 | 43.2% |
| 12 | 28.4% |
| 17 | 16.8% |
Appears in
Sources
Wang ES, Montesinos P, Foran J, Erba H, Rodríguez-Arbolí E, Fedorov K, et al. Ziftomenib in Relapsed or Refractory NPM1-Mutated AML. J Clin Oncol. 2025;43(31):3381-3390.
Wang ES, Issa GC, Erba HP, Altman JK, Montesinos P, DeBotton S, et al. Ziftomenib in relapsed or refractory acute myeloid leukaemia (KOMET-001): a multicentre, open-label, multi-cohort, phase 1 trial. Lancet Oncol. 2024;25(10):1310-1324.