Revumenib

1 INDICATIONS AND USAGE REVUFORJ is a menin inhibitor indicated for: the treatment of relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene ( KMT2A ) translocation as determined by an FDA-authorized test in adult and pediatric patients 1 year and older. ( 1 ) the treatment of relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 ( NPM1 ) mutation in adult and pediatric patients 1 year and older who have no satisfactory alternative treatment options. ( 1 ) Relapsed or Refractory Acute Leukemia REVUFORJ is indicated for the treatment of relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene ( KMT2A ) translocation as determined by an FDA-authorized test in adult and pediatric patients 1 year and older. REVUFORJ is indicated for the treatment of relapsed or refractory acute myeloid leukemia with a susceptible nucleophosmin 1 ( NPM1 ) mutation [see Dosage and Administration (2.1) , Clinical Pharmacology (12.1) , and Clinical Studies (14.1) ] in adult and pediatric patients 1 year and older who have no satisfactory alternative treatment options.

2 DOSAGE AND ADMINISTRATION Select patients for treatment with REVUFORJ based on the presence of a KMT2A translocation or an NPM1 mutation. ( 2.1 ) Administer REVUFORJ orally twice daily fasted or with a low-fat meal at approximately the same time each day. ( 2.2 ) See Full Prescribing Information for recommended REVUFORJ dosage regimen, dosage modifications, and administration instructions. ( 2.2 , 2.3 ) 2.1 Patient Selection Relapsed or Refractory Acute Leukemia with a KMT2A Translocation Select patients for treatment with REVUFORJ based on the presence of a KMT2A translocation [see Clinical Studies (14.1) ] . Information on FDA authorized tests for the detection of a KMT2A translocation to determine eligibility for treatment is available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?id=DEN240067 Relapsed or Refractory Acute Myeloid Leukemia with an NPM1 mutation Select patients for treatment with REVUFORJ based on the presence of an NPM1 mutation [see Clinical Pharmacology (12.1 ) and Clinical Studies (14.2) ] . An FDA-approved companion diagnostic for the detection of an NPM1 mutation is not currently available. 2.2 Recommended Dosage The recommended dosage of REVUFORJ varies by patient weight and concomitant use of strong CYP3A4 inhibitors. See Table 1 for the recommended dosage for patients 1 year and older. Do not start REVUFORJ until the WBC is reduced to less than 25 Gi/L. Continue REVUFORJ until disease progression or unacceptable toxicity. For patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response. Table 1. REVUFORJ Recommended Dosage for Patients 1 Year and Older *See Table 2 for the total tablet dosage by BSA (body surface area) for patients weighing less than 40 kg. Patient Weight Without Strong CYP3A4 Inhibitors With Strong CYP3A4 Inhibitors 40 kg or more 270 mg orally twice daily 160 mg orally twice daily Less than 40 kg 160 mg/m 2 orally twice daily* 95 mg/m 2 orally twice daily* Table 2: Recommended Dosage using Tablets* for Patients Weighing Less than 40 kg * If needed, attain the desired dose by combining different strengths of REVUFORJ tablets. BSA (m 2 ) REVUFORJ Dosage for 160 mg/m 2 REVUFORJ Dosage for 95 mg/m 2 1.4 220 mg twice daily 135 mg twice daily 1.3 220 mg twice daily 135 mg twice daily 1.2 185 mg twice daily 110 mg twice daily 1.1 185 mg twice daily 110 mg twice daily 1 160 mg twice daily 100 mg twice daily 0.9 135 mg twice daily 75 mg twice daily 0.8 135 mg twice daily 75 mg twice daily 0.7 110 mg twice daily 50 mg twice daily 0.6 100 mg twice daily 50 mg twice daily 0.5 75 mg twice daily 50 mg twice daily 0.4 50 mg twice daily 25 mg twice daily If the strong CYP3A4 inhibitor is discontinued, increase the REVUFORJ dose after at least 5 half-lives of the strong CYP3A4 inhibitor to the recommended dosage without strong CYP3A4 inhibitors (Table 1). Concurrent use of standard intrathecal chemotherapy prophylaxis is recommended for patients with risk of central nervous system relapse. Administration: Correct hypokalemia, hypomagnesemia, and other electrolyte abnormalities prior to treatment. Administer REVUFORJ twice daily fasted or with a low-fat meal (e.g., meals with approximately 400 calories, 25% or less fat). Administer REVUFORJ orally around the same time each day. Advise patients to swallow tablets whole and to not cut or chew tablets. If patients are unable to swallow tablets, they may be crushed and dispersed in water and taken within 2 hours of preparation [see Instructions for Use ] . If a dose of REVUFORJ is missed or not taken at the usual time, administer the dose as soon as possible on the same day and at least 12 hours prior to the next scheduled dose. Return to the normal schedule the following day. Do not administer 2 doses within 12 hours. 2.3 Dosage Modifications for Adverse Reactions Assess blood counts, electrolytes, and liver enzymes prior to the initiation of REVUFORJ and monthly thereafter. Perform an electrocardiogram (ECG) prior to the initiation of REVUFORJ, at least once a week for the first 4 weeks, and at least monthly thereafter. Monitor for QTc interval prolongation and manage any abnormalities promptly [see Warnings and Precautions (5.2) and Adverse Reactions (6.1) ] . Interrupt dosing or reduce dose for adverse reactions as per Table 3. Dose levels for dose reductions are listed in Table 4, Table 5, and Table 6. Table 3. Recommended Management and Dosage Modifications for Adverse Reactions *Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening. Severity as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0). **See Tables 4, 5 and 6 for the reduced dose levels. Adverse reaction Recommended action Differentiation Syndrome [see Warnings and Precautions (5.1) ] If differentiation syndrome is suspected, administer systemic corticosteroids and initiate hemodynamic monitoring until symptom resolution and for a minimum of 3 days. [see Warnings and Precautions (5.1) ] . Interrupt REVUFORJ if severe signs and/or symptoms persist for more than 48 hours after initiation of systemic corticosteroids, or earlier for life-threatening symptoms such as pulmonary symptoms requiring ventilator support [see Warnings and Precautions (5.1) ] . Resume REVUFORJ at the same dose when signs and symptoms improve to Grade 1* or lower. Noninfectious leukocytosis Initiate treatment with hydroxyurea in patients with an elevated or rapidly rising leukocyte count. Add leukapheresis if clinically indicated. Taper hydroxyurea only after leukocytosis improves or resolves. QTc interval greater than 480 msec to 500 msec [see Warnings and Precautions(5.2) ] Interrupt REVUFORJ. Check electrolyte levels. Correct hypokalemia and hypomagnesemia [see Warnings and Precautions (5.2) ] . Restart REVUFORJ at the same dose level after the QTc interval returns to less than or equal to 480 msec. QTc interval greater than 500 msec (Grade 3*) [see Warnings and Precautions (5.2) ] Interrupt REVUFORJ. Check electrolyte levels. Correct hypokalemia and hypomagnesemia [see Warnings and Precautions (5.2) ] . Restart REVUFORJ at the reduced dose level** after the QTc interval returns to less than or equal to 480 msec. QTc interval prolongation with signs/symptoms of life-threatening arrhythmia, Torsades de pointes, polymorphic ventricular tachycardia, signs/ symptoms of life-threatening arrhythmia (Grade 4*) [see Warnings and Precautions (5.2) ] . Permanently discontinue REVUFORJ. Potassium 3.6-3.9 mEq/L, and/or Magnesium 1.7-1.9 mg/dL or 0.66-0.81 mmol/L Supplement potassium and/or magnesium. Continue REVUFORJ. Potassium ≤ 3.5 mEq/L, and/or Magnesium ≤ 1.6 mg/dL or ≤ 0.65 mmol/L Supplement potassium and/or magnesium, and recheck levels within 24 hours. On recheck of potassium and magnesium labs within 24 hours, if potassium is greater than 3.5 mEq/L and/or magnesium is greater than 1.6 mg/dL, continue REVUFORJ. If potassium is less than 3.5 mEq/L and/or magnesium is less than 1.6 mg/dL, hold REVUFORJ and continue supplementation; resume REVUFORJ at the same dose level when the correction is complete. Other nonhematological adverse reactions Grade ≥ 3* [see Adverse Reactions (6.1) ] Interrupt REVUFORJ until recovery to Grade 1* or baseline. If recovered in ≤ 7 days, restart REVUFORJ at the same dose level. If the same Grade ≥ 3* toxicity recurs, interrupt REVUFORJ until recovery to Grade 1* or baseline. Restart REVUFORJ at the reduced dose level.** If recovered in > 7 days, restart REVUFORJ at the reduced dose level.** If the same Grade ≥ 3* toxicity recurs, discontinue REVUFORJ. Grade 4* neutropenia or thrombocytopenia [see Adverse Reactions (6.1) ] Interrupt REVUFORJ until recovery to Grade ≤ 2* or baseline. Restart REVUFORJ at the same dose level. If Grade 4* neutropenia or thrombocytopenia recurs without attributable cause, interrupt REVUFORJ until recovery to Grade ≤ 3*. Restart REVUFORJ at the reduced dose level.** Grade 3* or higher allergic reactions [see Adverse Reactions (6.1) ] Permanently discontinue REVUFORJ. Table 4. REVUFORJ Dosage Reduction for Adverse Reactions in Patients NOT on Strong CYP3A4 Inhibitors **See Table 6 for BSA-based dosage recommendations for the reduced dosage of 95 mg/m 2 twice daily. Patients Weighing 40 kg or Greater at Starting Dose 270 mg orally twice daily Patients Weighing Less Than 40 kg at Starting Dose 160 mg/m 2 orally twice daily Reduced Dose 160 mg orally twice daily 95 mg/m 2 orally twice daily* Table 5. REVUFORJ Dosage Reduction for Adverse Reactions in Patients on Strong CYP3A4 Inhibitors *See Table 6 for BSA-based dosage recommendations for the reduced dosage of 65 mg/m 2 twice daily. Patients Weighing 40 kg or Greater at Starting Dose 160 mg orally twice daily Patients Weighing Less Than 40 kg at Starting Dose 95 mg/m 2 orally twice daily Reduced Dose 110 mg orally twice daily 65 mg/m 2 orally twice daily* Table 6: Recommended Reduced Dosage Using Tablets* for Patients Weighing Less than 40 kg * If needed, attain the desired dose by combining different strengths of REVUFORJ tablets. BSA (m 2 ) REVUFORJ Dosage for 95 mg/m 2 REVUFORJ Dosage for 65 mg/m 2 1.4 135 mg twice daily 100 mg twice daily 1.3 135 mg twice daily 75 mg twice daily 1.2 110 mg twice daily 75 mg twice daily 1.1 110 mg twice daily 75 mg twice daily 1 100 mg twice daily 50 mg twice daily 0.9 75 mg twice daily 50 mg twice daily 0.8 75 mg twice daily 50 mg twice daily 0.7 50 mg twice daily 50 mg twice daily 0.6 50 mg twice daily 25 mg twice daily 0.5 50 mg twice daily 25 mg twice daily 0.4 25 mg twice daily 25 mg twice daily

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Differentiation Syndrome [see Warnings and Precautions (5.1) ] QTc Interval Prolongation and Torsades de Pointes [see Warnings and Precautions (5.2) ] The most common adverse reactions (≥ 20%) including laboratory abnormalities, are phosphate increased, hemorrhage, nausea, infection without identified pathogen, aspartate aminotransferase increased, alanine aminotransferase increased, creatinine increased, musculoskeletal pain, febrile neutropenia, electrocardiogram QT prolonged, potassium decreased, parathyroid hormone intact increased, alkaline phosphatase increased, diarrhea, bacterial infection, triglycerides increased, differentiation syndrome, fatigue, edema, viral infection, phosphate decreased, decreased appetite, and constipation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Syndax Pharmaceuticals, Inc., at 1-888-539-3REV or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of REVUFORJ reflects exposure in 241 patients (207 adult and 34 pediatric patients) with relapsed or refractory (R/R) acute leukemia with a KMT2A translocation or an NPM1 mutation treated with REVUFORJ at a dose approximately equivalent to 160 mg in adults orally twice daily with a strong CYP3A4 inhibitor [see Clinical Studies (14) ] . The median duration of exposure to REVUFORJ was 2.5 months (range < 1 to 40 months), and 10% of patients were exposed for more than 6 months. Fatal adverse reactions occurred in 9 (4%) patients who received REVUFORJ, including 4 with sudden death, 2 with differentiation syndrome, 2 with hemorrhage, and 1 with cardiac arrest. Serious adverse reactions were reported in 184 (76%) patients. The most frequent serious adverse reactions (≥ 10%) were infection (29%), febrile neutropenia (20%), bacterial infection (15%), differentiation syndrome (13%), and hemorrhage (11%). Adverse reactions leading to dose interruption occurred in 49% of patients. The most common adverse reactions (≥ 5%) leading to dose interruption were electrocardiogram QT prolonged, infection, febrile neutropenia, differentiation syndrome, nausea, and hypokalemia. Adverse reactions leading to dose reduction occurred in 12% of patients who received REVUFORJ. Adverse reactions leading to a dose reduction (≥ 5%) included electrocardiogram QT prolonged. Adverse reactions leading to permanent discontinuation occurred in 20% of patients. Adverse reactions resulting in permanent discontinuation (> 1%) included infection. The most common (≥ 20%) adverse reactions were phosphate increased, hemorrhage, nausea, infection without identified pathogen, aspartate aminotransferase increased, alanine aminotransferase increased, creatinine increased, musculoskeletal pain, febrile neutropenia, electrocardiogram QT prolonged, potassium decreased, parathyroid hormone intact increased, alkaline phosphatase increased, diarrhea, bacterial infection, triglycerides increased, differentiation syndrome, fatigue, edema, viral infection, phosphate decreased, decreased appetite, and constipation. The common adverse reactions are summarised in Table 7. Table 7. Adverse Reactions Reported in ≥ 20% (Any Grade) or ≥ 5% (Grade 3 or 4) in Patients with R/R Acute Leukemia # Includes the following fatal adverse reactions: DS (n=2); hemorrhage (n=2) a – Includes nausea and vomiting b – includes diarrhea, colitis, and neutropenic colitis c – includes epistaxis, contusion, petechiae, gingival bleeding, hematoma, hemoptysis, hemorrhoidal hemorrhage, mouth hemorrhage, hematuria, ecchymosis, hemorrhage intracranial, subdural hematoma, upper gastrointestinal hemorrhage, gastrointestinal hemorrhage, vaginal hemorrhage, post- procedural hemorrhage, rectal hemorrhage, subarachnoid hemorrhage, vitreous hemorrhage, catheter site hemorrhage, conjunctival hemorrhage, hematochezia, melaena, retinal hemorrhage, anal hemorrhage, brain stem hemorrhage, cystitis hemorrhagic, eye hematoma, genital contusion, injection site hematoma, lower gastrointestinal hemorrhage, mucosal hemorrhage, oral blood blister, oral contusion, oral purpura, pulmonary hemorrhage, shock hemorrhagic, spinal subdural hematoma d – includes disseminated intravascular coagulation, pulmonary embolism, cerebrovascular accident, superficial vein thrombosis, deep vein thrombosis, acute myocardial infarction, cerebral infarction, embolism, hemorrhoids thrombosed, medical device site thrombosis, myocardial infarction, renal infarction, splenic infarction, thrombosis, and transient ischaemic attack e – includes pneumonia, sepsis, urinary tract infection, septic shock, sinusitis, skin infection, upper respiratory tract infection, osteomyelitis, device related infection, enterocolitis infectious, conjunctivitis, hordeolum, rhinitis, acute sinusitis, diverticulitis, endocarditis, perirectal abscess, rectal abscess, tooth abscess, abscess limb, appendicitis, bronchitis, epididymitis, eye infection, gastroenteritis, infection, mucosal infection, neutropenic sepsis, rash pustular, retinitis, shock, sialadenitis, soft tissue infection, tooth infection, vascular device infection f – includes bacteraemia, clostridium difficile infection, cellulitis, escherichia bacteremia, paronychia, staphylococcal bacteremia, streptococcal bacteremia, alpha hemolytic streptococcal infection, clostridium difficile colitis, clostridium test positive, enterobacter infection, enterobacter sepsis, enterococcal bacteremia, escherichia urinary tract infection, pseudomonal bacteremia, pseudomonas infection, skin bacterial infection, bacteriuria, cellulitis staphylococcal, cornyebacterium bacteremia, enterobacter bacteremia, enterococcal infection, folliculitis, klebsiella infection, klebsiella sepsis, lactobacillus bacteremia, meningitis bacterial, stenotrophomonas infection g – includes COVID-19, rhinovirus infection, herpes simplex reactivation, herpes simplex, herpes zoster, oral herpes, respiratory syncytial virus infection, enterovirus infection, adenovirus infection, coronavirus infection, cytomegalovirus infection, cytomegalovirus infection reactivation, cytomegalovirus viremia, COVID-19 pneumonia, cytomegalovirus test positive, enterovirus test positive, Epstein-Barr virus infection, herpes simplex pharyngitis, herpes virus infection, influenza, norovirus infection, parainfluenzae virus infection, pneumonia cytomegaloviral viremia h – includes arthralgia, back pain, pain in extremity, neck pain, myalgia, musculoskeletal chest pain, myositis, flank pain, musculoskeletal discomfort, and musculoskeletal pain i – includes fatigue, asthenia, malaise j – includes edema peripheral, generalised edema, edema, localized edema, peripheral swelling REVUFORJ N = 241 TEAE All Grades % Grade 3 or 4 % Gastrointestinal disorders Nausea a 48 5 Diarrhea b 29 5 Constipation 20 0 Vascular disorders Hemorrhage #,c 48 10 Thrombosis d 11 6 Infections and infestations Infection without identified pathogen e 46 30 Bacterial infection f 27 18 Viral Infection g 23 6 Blood and lymphatic system disorders Febrile neutropenia 37 35 Musculoskeletal and connective tissue disorders Musculoskeletal pain h 37 6 Investigations Electrocardiogram QT prolonged 36 17 Neoplasms benign, malignant and unspecified (including cysts and polyps) Differentiation syndrome# 25 12 General disorders and administration site conditions Fatigue i 24 5 Edema j 24 0 Metabolism and nutrition disorders Decreased appetite 20 5 Clinically relevant adverse reactions in less than 20% of patients who received REVUFORJ include: Cardiac disorders: Premature ventricular complex, cardiac failure, pericardial effusion, ventricular tachycardia, cardiac arrest Endocrine disorders : Hyperparathyroidism Eye disorders : Cataract Gastrointestinal disorders : Abdominal pain General disorders and administration site conditions : Sudden death Immune system disorders : Drug hypersensitivity Metabolism and nutrition disorders : Hyponatremia, hyperkalemia Nervous system disorders : Taste disorder, syncope, headache, paresthesia Renal disorders : Renal impairment Skin and subcutaneous disorders : Rash Changes in selected post-baseline laboratory values that were observed in patients with relapsed or refractory acute leukemia are shown in Table 8. Table 8. Selected New or Worsening Laboratory Abnormalities in Patients with R/R Acute Leukemia *The denominator used to calculate the rate varied from 139 to 240 based on the number of patients with a baseline value and at least one post baseline value. REVUFORJ Laboratory Abnormality Grades 1-4* % Grades 3-4 % Phosphate increased 51 - Aspartate aminotransferase increased 44 6 Alanine aminotransferase increased 40 8 Creatinine increased 38 2 Potassium decreased 34 12 Parathyroid hormone, intact increased 34 - Alkaline phosphatase increased 33 <1 Triglycerides increased 27 3 Phosphate decreased 25 - Cholesterol increased 17 0 Calcium corrected increased 15 0

12.3 Pharmacokinetics The pharmacokinetics of revumenib were characterized in patients with relapsed or refractory acute leukemia with a KMT2A translocation or an NPM1 mutation following single and multiple oral administration of revumenib with or without strong CYP3A4 inhibitors. Steady-state pharmacokinetic parameters are presented as geometric mean [coefficient of variation (%CV)] unless otherwise specified. Table 9. Revumenib Pharmacokinetics in Patients with R/R Acute Leukemia with a KMT2A translocation or an NPM1 mutation Abbreviations: C max = maximum plasma concentration; AUC = area under the time concentration curve; T max = time to peak concentration a - Steady-state b - Dosage range of 113 mg to 339 mg (1.26 times the highest adult approved recommended dosage) c - Approximately 400-500 calories, 25% of calories from fat d - Independent of concentration e - M1 contributes to revumenib’s clinically significant effects on QTc [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2)] but does not contribute to its efficacy at the approved recommended dosage f - A single dose of radiolabeled revumenib 276 mg (1.02 times the highest adult approved recommended dosage) to adult patients with relapsed/refractory acute leukemia Parameter Dosage 160 mg twice daily (with strong CYP3A4 inhibitors) 270 mg twice daily (without strong CYP3A4 inhibitors) General Information Exposure ba C max (ng/mL) 3028 (51%) 2344 (81%) AUC 0-12h (ng•h/mL) 20,050 (62%) 11,520 (70%) Dose Proportionality b Dose proportional increases in C max and AUC 0-12h Time to Steady-State 2 days Accumulation a 2-fold Absorption T max Median (range) hours 2 (0-12) 1 (0.5-4) Effect of Food Low fat meal c No clinically significant differences in revumenib pharmacokinetics observed (C max and AUC decreased by 27% and 12% respectively) Distribution Apparent Volume of Distribution a (L) 63 (84%) Protein Binding d 90% Blood to plasma ratio 0.8 Elimination Half-Life a (hours) 6.4 (52%) 3.0 (49%) Apparent Clearance a (L/h) 7 (64%) 20 (112%) Metabolism Primary Pathway CYP3A4 Active Metabolite M1 f Excretion f Feces Approximately 52% (7% unchanged) Urine Approximately 25% (6% unchanged) Specific Populations No clinically significant differences in the pharmacokinetics of revumenib were observed based on age (1 to 84 years), race (67% White, 7% Asian, 8% Black), sex, mild to moderate (CLcr 30 to 89 mL/min) renal impairment, and mild (total bilirubin ≤ upper limit of normal [ULN] and AST > ULN or total bilirubin > 1 to 1.5 × ULN and any AST) or moderate (total bilirubin > 1.5 to 3 × ULN and any AST) hepatic impairment. The effect of severe renal impairment (CLcr less than 30 mL/min), end- stage renal disease (CLcr less than 15 mL/min), or severe (total bilirubin > 3 × ULN and any AST) hepatic impairment is unknown. Body weight (6-151 kg) has a significant effect on the pharmacokinetics of revumenib, with higher revumenib exposures in patients with lower body weight (less than 40 kg). This supports the use of BSA-based dosage in patients weighing less than 40 kg. Pediatric Patients Revumenib geometric mean (CV%) steady-state Cmax was 3137 (39%) ng/mL and AUC0-tau was 14,630 (55%) ng·hr/mL following 95 mg/m2 twice daily with strong CYP3A4 inhibitors. Revumenib predicted geometric mean (%CV) steady-state Cmax was 1597 (70%) ng/mL and AUC0- tau was 12,570 (56%) ng·hr/mL following 160 mg/m 2 twice daily without strong CYP3A4 inhibitors. Drug Interaction Studies Clinical Studies Strong CYP3A4 Inhibitors: Revumenib AUC and Cmax is increased by 2-fold following concomitant use of multiple doses of revumenib with certain azole antifungals that are strong CYP3A4 inhibitors (i.e., posaconazole, itraconazole, and voriconazole). Similarly, revumenib AUC and Cmax is increased by 2.5-fold following concomitant use of multiple doses of revumenib with cobicistat (strong CYP3A4 inhibitor). Strong and Moderate CYP3A4 Inducers: Revumenib exposure is expected to decrease and M1 exposure is expected to increase with strong and moderate CYP3A4 inducers. Other Drugs: No clinically significant differences in revumenib pharmacokinetics were observed when used concomitantly with fluconazole (moderate CYP3A4 inhibitor), isavuconazole (moderate CYP3A4 inhibitor). In Vitro Studies Cytochrome P450 (CYP) Enzymes: Revumenib inhibits CYP3A4, but does not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1. Revumenib does not induce CYP1A2, CYP2B6, and CYP3A4. Transporter Systems: Revumenib is a substrate of OCT1, OCT2, OAT1, OAT3, and MATE1, but is not a substrate of P-gp, BCRP, OATP1B1, OATP1B3, MATE2-K, or BSEP. M1 is a substrate of OATP1B1, but is not a substrate of P-gp, BCRP, OCT2, OAT1, OAT3, OATP1B3, MATE1, or MATE2-K. Revumenib inhibits MATE1, but does not inhibit P-gp, BCRP, OCT1, OCT2, OAT1, OAT3, OATP1B1, OATP1B3, BSEP, and MATE2-K. M1 inhibits MATE1, but does not inhibit OAT1, OAT3, OCT2, OATP1B1, OATP1B3, and MATE2-K.