marked.bio

FLT3 inhibitor · small molecule

midostaurin

5 active trials across 2 of our biomarkers, targeting FLT3 (multi-kinase). 2 active approvals for a biomarker on marked.bio.

Also known as PKC412, Rydapt.

Counts only trials that select patients by one of the biomarkers on marked.bio, not every trial of this drug.

Approvals and pivotal results

Biomarker-selected approvals in the United States and the European Union, with the pivotal trial's results and side effects where we have them. Results from different trials are not directly comparable.

TherapyBiomarkerTumourUnited StatesEuropean Union
midostaurin with standard induction and consolidation chemotherapy
FDA, 2017
newly diagnosed FLT3-mutated, with cytarabine/daunorubicin induction and cytarabine consolidation FDA approval 28/04/2017; companion test LeukoStrat CDx FLT3 Mutation Assay. Source
EU (EMA), 2017
newly diagnosed FLT3 mutation-positive, with daunorubicin/cytarabine induction and high-dose cytarabine consolidation, then maintenance EU marketing authorisation 18/09/2017. Source
Rydapt 		FLT3 mutation (ITD/TKD) AML Approved 2017 Approved 2017

RATIFY (CALGB 10603) vs placebo + chemotherapy, 360 vs 357 patients
EFS 8.2 months vs 3.0 months, HR 0.78 (0.66-0.93)OS 74.7 months vs 25.6 months, HR 0.77 (0.63-0.95)

Stopped for side effects 9%Fatal none apart from disease progression

Trial details and side effects
Patients
newly diagnosed FLT3-mutated AML, age 18-59 (NCT00651261)
Most common side effects
febrile neutropenia 83%, nausea 83%, mucositis 66%, vomiting 61%, headache 46%, petechiae 36%, musculoskeletal pain 33%, nosebleeds 28% (345 patients)
Notes
FDA approval as reported by OncLive (2017). Side effects: Rydapt US label, section 6 (RATIFY, with chemotherapy).
Source
US approval report

Biomarkers

BiomarkerActive trialsAll trialsFurthest active phase
FLT3 mutation (ITD/TKD) 5 23 Phase 3
NPM1 mutation 1 1 Phase 1

Sponsors

Industry sponsors leading active biomarker-selected trials of midostaurin.

  1. Novartis 1

Trials

5 of 23 trials shown

  1. A Study of Gilteritinib Versus Midostaurin in Combination With Induction and Consolidation Therapy Followed by One-year Maintenance in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndromes With Excess Blasts-2 With FLT3 Mutations Eligible for Intensive Chemotherapy

    Active, not recruiting Phase 3 Stichting Hemato-Oncologie voor Volwassenen Nederland Started 2019Primary completion 2025-10 NCT04027309

    gilteritinib FDA EUmidostaurin FDA EU

    … blasts-2 (EB2) defined according to WHO criteria (appendix A), with centrally documented FLT3 gene mutation (either TKD or ITD or both).

    FLT3 mutation (ITD/TKD)Acute Myeloid Leukemia, Myelodysplastic Syndrome With Excess Blasts-2

  2. Venetoclax in Association With 3+7 and Midostaurin in FLT3-mutated Acute Myeloid Leukemia

    Not yet recruiting Phase 1/2 University Hospital, Bordeaux Started 2026Primary completion 2027-09 NCT07726576

    venetoclaxmidostaurin FDA EU

    Documented FLT3 gene mutation (-TKD D835 or I836 or -ITD or both) FLT3-ITD is assessed by DNA fragment analysis.

    FLT3 mutation (ITD/TKD)Leukemia, Myeloid, Acute

  3. Combination of Midostaurin and Gemtuzumab Ozogamicin in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC)

    Recruiting Phase 1/2 Technische Universität Dresden Started 2020Primary completion 2027-04 NCT04385290

    cytarabinedaunorubicinmidostaurin FDA EUgemtuzumab ozogamicin

    FLT3-ITD or

    FLT3 mutation (ITD/TKD)Acute Myeloid Leukemia

  4. A Global Study of Midostaurin in Combination With Chemotherapy to Evaluate Safety, Efficacy and Pharmacokinetics in Newly Diagnosed Pediatric Patients With FLT3 Mutated AML

    Active, not recruiting Phase 2 Novartis Started 2019Primary completion 2029-05 NCT03591510

    midostaurin FDA EUfludarabinecytarabinedaunorubicinidarubicinmitoxantroneetoposide

    …Evaluate Safety, Efficacy and Pharmacokinetics in Newly Diagnosed Pediatric Patients With FLT3 Mutated AML

    FLT3 mutation (ITD/TKD)FLT3-mutated Acute Myeloid Leukemia

  5. Revumenib in Combination With 7+3 + Midostaurin in AML

    Recruiting Phase 1 Richard Stone, MD Started 2024Primary completion 2027-03 NCT06313437

    revumenibmidostaurin FDA EUcytarabinedaunorubicin

    Presence of FLT3-ITD and/or TKD mutation(s) AND NPM1 mutation in bone marrow or peripheral blood

    FLT3 mutation (ITD/TKD)NPM1 mutationAcute Myeloid Leukemia, AML, Adult, AML With Gene Mutations, AML