Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Revumenib · 7 trials · 20 indications
RFS is defined as the time from randomization to the date of relapse or the date of death from any cause, whichever comes first. RFS is defined as the time from randomization to the date of relapse or the date of death from any cause, whichever comes first.
Detailed DLT consideration outline in protocol section 5.4.
MTD is determined by the number of patients who experience a DLT. See previous primary outcome measure for the DLT definition. If 0 out of 3 participants experience DLT, next dose level will be proceeded. If \>=1 out of the group suffer DLT, dose escalation will be stopped and 3 additional participants will be entered at the next lowest dose level. If \<=1 out of 6 DLTs, this dose level is considered as MTD.
The RP2D is determined by a combination of the MTD (see previous primary outcome measure), pharmacokinetics, pharmacodynamics and response rate to different doses of revumenib in combination with chemotherapy and the FLT3 inhibitor midostaurin.
(COHORT-1) Dose limiting toxicity (DLT) defined as according to the NCI CTCAE v6. AEs attributable to the study agents (possibly / probably / definitely related) will count towards the toxicity stopping boundaries. These include, but not limited to, neutrophil count decreased, thrombocytopenia, and other non-hematologic AEs
(COHORT-1) Number of treatment specific adverse events (AEs) by CTCAE v6.0 (COHORT-2) during dose escalation phase
(COHORT-2) Overall response rate (ORR) defined as CR, PR, or CI by the revised IWG-MRT and ELN criteria after 6 cycles of therapy (each cycle is one month.)
Assessed by the NCI CTCAE version 5.0 (Phase 1)
Assessed by the NCI CTCAE version 5.0 (Phase 1)
Maximum plasma concentration (Cmax) of revumenib and relevant metabolites (Phase 1)
Time to observed maximum plasma concentration of revumenib and relevant metabolites (Phase 1)
Area under the plasma concentration-time curve from time 0 to time of last measurable concentration (AUC0-t) of revumenib and relevant metabolites (Phase 1)
To assess the complete remission (CR) and complete remission with partial hematologic recovery (CRh) rate (Phase 2 \[Cohorts 2A-2C\])
Assessed by the NCI CTCAE version 5.0 (Phase 2 \[Cohorts 2A-2C\])
Cmax of revumenib (Phase 2 \[Cohort 2D\])
Area under the plasma concentration-time curve from time 0 to the end of the dosing interval (AUC0-tau) of revumenib (Phase 2 \[Cohort 2D\])
| Arm | Type | Description |
|---|---|---|
| Revumenib + Intensive Chemotherapy | EXPERIMENTAL | Participants will receive revumenib plus an intensive chemotherapy regimen. |
| Placebo + Intensive Chemotherapy | PLACEBO_COMPARATOR | Participants will receive placebo plus an intensive chemotherapy regimen. |
| Revumenib BID | EXPERIMENTAL | 160 mg/oral/q12h for patients not taking strong CYP3A4 inhibitor 110 mg/oral/q12h for patients taking strong CYP3A4 inhibitor |
| Placebo BID | PLACEBO_COMPARATOR | 160 mg/oral/q12h for patients not taking strong CYP3A4 inhibitor 110 mg/oral/q12h for patients taking strong CYP3A4 inhibitor |
| Dose Escalation Revumenib | EXPERIMENTAL | Standard 3+3 design for a recommended phase 2 dose of Revumenib per dose-limiting toxicity rules. Cycles are 28 days. * Baseline * Induction Cycle: * Days 1-3: Predetermined dose of Daunorubicin 1x daily * Days 1-7: Predetermined dose of Cytarabine * Days 8-21: Predetermined dose of Midostaurin 2x daily * Days 8-28: Predetermined dose of Revumenib 2x daily * End of Induction visit * Follow-up * Reinduction Cycle: Therapy will be administered in the hospital * Days 1-2: Predetermined dose of Daunorubicin 1x daily * Days 1-5: Predetermined dose of Cytarabine * Days 8-21: Predetermined dose of Midostaurin 2x daily * Days 8-28: Predetermined dose of Revumenib 2x daily * End of reinduction visit * Follow-up * Consolidation Cycle: Therapy will be administered in the hospital * Days 1, 3, and 5: Predetermined dose of Cytarabine * Days 8-21: Predetermined dose of Midostaurin 2x daily * Days 8-28: Predetermined dose of Revumenib 2x daily * End of consolidation visit * Follow up |
| Dose-Expansion Revumenib | EXPERIMENTAL | Cycles are 28 days * Baseline visit and assessments * Induction Cycle: * Days 1-3: Predetermined dose of Daunorubicin 1x daily * Days 1-7: Predetermined dose of Cytarabine * Days 8-21: Predetermined dose of Midostaurin 2x daily * Days 8-28: Predetermined dose of Revumenib 2x daily * End of Induction visit * Follow-up * Reinduction Cycle: Therapy will be administered in the hospital * Days 1-2: Predetermined dose of Daunorubicin 1x daily * Days 1-5: Predetermined dose of Cytarabine * Days 8-21: Predetermined dose of Midostaurin 2x daily * Days 8-28: Predetermined dose of Revumenib 2x daily * End of Reinduction visit * Follow-up * Consolidation Cycle: Therapy will be administered in the hospital * Days 1, 3, and 5: Predetermined dose of Cytarabine * Days 8-21: Predetermined dose of Midostaurin 2x daily * Days 8-28: Predetermined dose of Revumenib 2x daily * End of Consolidation visit * Follow up |
| COHORT-1 (revumenib monotherapy) | EXPERIMENTAL | Revumenib monotherapy utilizing a 3+3 dose-escalation design |
| COHORT-2 (revumenib added to JAK inhibitor therapy) | EXPERIMENTAL | Dosage of revumenib from Cohort 1 plus JAK inhibitor therapy (ruxolitinib, fedratinib, or momelotinib) |
| Revumenib | EXPERIMENTAL | Participants will be administered a single dose of revumenib (containing \~100 microcuries \[14C\]-revumenib) in the AME part of the study. Each dose administered after the first dose in the AME part of the study will be nonradiolabeled revumenib. revumenib may continue to be administered following completion of the AME part of the study. Doses will be administered in continuous 28-day cycles until either PD or unacceptable toxicity. |
| Revumenib and Chemotherapy Regimen 1 | EXPERIMENTAL | Participants with acute lymphoblastic leukemia/mixed phenotype acute leukemia (ALL/MPAL) will receive revumenib every 12 hours in combination with 2 treatment cycles of Chemotherapy Regimen 1. |
| Revumenib and Chemotherapy Regimen 2 | EXPERIMENTAL | Participants with ALL/MPAL or acute myeloid leukemia (AML) will receive revumenib every 12 hours in combination with 2 treatment cycles of Chemotherapy Regimen 2. |
| Name | Type | Description |
|---|---|---|
| Revumenib | DRUG | Participants will receive revumenib orally. |
| Placebo | DRUG | Participants will receive placebo (non-active agent) orally. |
| Intensive Chemotherapy Regimen | DRUG | Participants will receive an intensive chemotherapy regimen of cytarabine and daunorubicin by intravenous (IV) infusion. |
| Midostaurin | DRUG | Kinase inhibitor, capsule taken orally per protocol. |
| Cytarabine | DRUG | Antineoplastic agent, via intravenous (into the vein) infusion per protocol. |
| Daunorubicin | DRUG | Antineoplastic agent, via intravenous (into the vein) infusion per protocol. |
| Ruxolitinib | DRUG | Part of routine care. Participants to continue on dosage as prescribed by provider, 5 to 20 mg BID |
| FEDRATINIB | DRUG | Part of routine care. Participants to continue on dosage as prescribed by provider, 100 mg to 400 mg daily. |
| Momelotinib | DRUG | Part of routine care. Participants to continue on dosage as prescribed by provider, 100 mg to 200 mg daily. |
| Chemotherapy Regimen 1 | DRUG | Participants will receive 2 treatment cycles of chemotherapy. During Cycle 1, participants will receive prednisone, vincristine, pegaspargase/calaspargase pegol-mknL, and daunorubicin. During Cycle 2, participants will receive etoposide and cyclophosphamide. |
| Chemotherapy Regimen 2 | DRUG | Participants will receive 2 treatment cycles of chemotherapy. During Cycles 1 and 2, participants will receive fludarabine and cytarabine. |
| cobicistat | DRUG | Phase 1 Arm C participants will receive 150 mg cobicistat daily. |
Key Inclusion Criteria: * Participants must have newly diagnosed and previously untreated AML and be candidates for intensive chemotherapy. * Presence of an NPM1 mutation. * Eastern Cooperative Oncology Group performance status ≤2 (≤1 if \>65 years old); Karnofsky or Lansky ≥40. * Have a life expec...
Revumenib is an investigational small molecule being studied for acute leukemias, including acute myeloid leukemia, acute lymphoblastic leukemia, and mixed lineage acute leukemia, as well as for myelofibrosis. It is being evaluated in patients with relapsed or refractory disease, including those with MLL/KMT2A gene rearrangements or NPM1 mutations.
Revumenib is a kinase inhibitor, belonging to the -nib class of small molecules. It is being studied in oncology for its activity against leukemias with specific genetic alterations, such as MLL/KMT2A rearrangements or NPM1 mutations.
Revumenib is being developed by Syndax Pharmaceuticals, Inc., a biopharmaceutical company traded on NASDAQ under the ticker symbol SNDX. The company is conducting clinical trials to evaluate the drug's safety and efficacy in various hematologic malignancies.
Revumenib is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. It has received several FDA designations, including Priority Review, Orphan Drug, Fast Track, and Breakthrough Therapy, reflecting its potential in treating serious conditions.
Revumenib is being studied in multiple Phase 1 trials. NCT04065399 is recruiting patients with relapsed/refractory leukemias, including those with MLL/KMT2A rearrangements or NPM1 mutations. NCT05326516, a completed study, evaluated Revumenib with chemotherapy in relapsed/refractory acute leukemia. NCT05406817, also completed, studied radiolabeled Revumenib in adults with acute leukemia. NCT07734077 is planned for patients with myelofibrosis.
Revumenib is the generic name for the drug formerly known as SNDX-5613, developed by Syndax Pharmaceuticals. It is a small molecule kinase inhibitor being investigated for the treatment of acute leukemias and myelofibrosis.