Drug Trials Snapshots: REVUFORJ
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the REVUFORJ Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
REVUFORJ (revumenib)
REV-you-forj
Syndax Pharmaceuticals, Inc.
Approval date: November 15, 2024
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
REVUFORJ is a cancer drug that is used to treat adults and children 1 year and older with acute leukemia with a lysine methyltransferase 2A gene translocation (KMT2A) whose disease has come back or has not improved after previous treatment(s).
How is this drug used?
REVUFORJ is a tablet that is taken orally twice a day.
Who participated in the clinical trials?
The FDA approved REVUFORJ based on evidence in 104 patients from one clinical trial (AUGMENT 101) with acute leukemia with a KMT2A translocation whose disease has come back or has not improved after previous treatment(s). The trial was conducted at 57 sites in 9 countries including the United States, Australia, Canada, France, Germany, Italy, Israel, Lithuania, and Netherlands. The study included 98 patients from the United States.
The number of patients representing efficacy findings differs from the number of patients representing safety due to different pools of study participants analyzed for efficacy and safety.
How were the trials designed?
REVUFORJ was evaluated in a single-arm cohort of AUGMENT 101, an open label, multi-center trial in patients with acute leukemia with a KMT2A translocation whose disease came back or did not improve after previous treatment. The primary endpoint was rate of complete remission (CR) and complete remission with partial hematologic recovery (CRh).
How were the trials designed?
The efficacy of REVUFORJ was evaluated in a single-arm cohort of an open-label, multi-center trial (NCT04065399/AUGMENT-101) in adult and pediatric patients at least 30 days old with relapsed or refractory (R/R) acute leukemia with a KMT2A translocation. Patients with an 11q23 partial tandem duplication were excluded. Eligibility required a QTcF <450 msec at study baseline. Treatment consisted of REVUFORJ at a dose approximately equivalent to 160 mg in adults orally twice daily with a strong CYP3A4 inhibitor until disease progression, unacceptable toxicity, failure to achieve morphological leukemia-free state by four cycles of treatment, or hematopoietic stem cell transplantation.
Efficacy was established on the basis of the rate of CR+CRh, the duration of CR+CRh, and the rate of conversion from transfusion dependence to transfusion independence.
The safety of REVUFORJ was evaluated in 135 patients (104 adult and 31 pediatric) from two trials (NCT04065399/AUGMENT-101 and NCT05406817) with R/R acute leukemia with a KMT2A translocation. Treatment consisted of REVUFORJ at a dose approximately equivalent to 160 mg in adults orally twice daily with a strong CYP3A4 inhibitor. The median duration of exposure to REVUFORJ was 2.3 months (range <1 to 23 months), and 3% of patients were exposed for more than 6 months.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the clinical trial used to evaluate the efficacy of REVUFORJ.
Figure 1. Baseline Demographics by Sex, Efficacy Population
Source: Adapted from FDA Review
Figure 2 summarizes how many patients by race were enrolled in the clinical trial used to evaluate the efficacy of REVUFORJ.
Figure 2. Baseline Demographics by Race, Efficacy Population
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by age were enrolled in the clinical trial used to evaluate the efficacy of REVUFORJ.
Figure 3. Baseline Demographics by Age, Efficacy Population
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by ethnicity were enrolled in the clinical trial used to evaluate the efficacy of REVUFORJ.
Figure 4. Baseline Demographics by Ethnicity, Efficacy Population
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographic and Disease Characteristics, Efficacy Population
Demographic and Disease Characteristics | REVUFORJ N=104 |
|---|---|
Age, years |
|
Median (min, max) | 37 (1, 79) |
Age group, years, n (%) |
|
<17 | 25 (24) |
≥17 | 79 (76) |
Sex, n (%) |
|
Male | 37 (36) |
Female | 67 (64) |
Race, n (%) |
|
Black or African American | 8 (8) |
Asian | 10 (10) |
White | 75 (72) |
Multiple | 1 (1) |
Unknown | 10 (10) |
Ethnicity, n (%) |
|
Hispanic or Latino | 23 (22) |
Not Hispanic or Latino | 76 (73) |
Unknown | 5 (5) |
Disease Characteristics |
|
Leukemia morphological type, n (%) |
|
Acute myeloid leukemia (AML) | 86 (83) |
Acute lymphoblastic leukemia (ALL) | 16 (15) |
Mixed phenotype acute leukemia (MPAL) | 2 (2) |
Translocations1, n (%) |
|
t(9;11) | 23 (22) |
t(11;19) | 20 (19) |
t(6;11) | 10 (10) |
t(10;11) | 10 (10) |
t(4;11) | 7 (7) |
t(1;11) | 3 (3) |
t(11;17) | 2 (2) |
t(11;22) | 2 (2) |
t(11;16) | 1(1) |
KMT2A fusion partner unknown | 26 (25) |
Disease status, n (%) |
|
Primary refractory | 22 (21) |
Untreated relapse | 21 (20) |
Refractory relapse | 61 (59) |
Prior treatment |
|
Number of prior regimens, median (range) | 2 (1, 11) |
Prior stem cell transplantation, n (%) | 46 (44) |
Number of prior relapses, n (%) |
|
0 | 22 (21) |
1 | 55 (53) |
2 | 20 (19) |
≥3 | 7 (7) |
Source: Adapted from FDA Review
Abbreviations: KMT2A, lysine methyltransferase 2A
What are the benefits of this drug?
The trial measured the number of patients with CR+CRh. In the trial, 22 of the 104 patients (21.2%) experienced CR+CRh, with a median duration of 6.4 months.
Of the 22 patients who achieved CR or CRh, the median time to CR or CRh was 1.9 months.
Of the 83 patients on the trial who were dependent on red blood cell (RBC) and/or platelet transfusions when starting treatment, 12 (14%) became independent of RBC and platelet transfusions during any 56-day period after starting treatment. Of the 21 patients who were independent of both RBC and platelet transfusions when starting treatment, 10 (48%) remained independent during after starting treatment.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2. Efficacy Results, Efficacy Population
Endpoint | REVUFORJ N=104 | 95% CI |
|---|---|---|
CR1+CRh2 n (%) | 22 (21.2) | 13.8, 30.3* |
Median DOCR+CRh3 (months) | 6.4* | 2.7, NE |
CR n (%) | 13 (12.5) | 6.8, 20.4* |
Median DOCR4 (months) | 4.3* | 1.0, NE |
CRh n (%) | 9 (8.7) | 4.0, 15.8* |
Median DOCRh5 (months) | 6.4* | 1.9, NE |
Source: REVUFORJ Prescribing information
1 CR is defined as bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC ≥1.0 × 109/L and platelet count ≥100 × 109/L.
2 CRh is defined as bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; residual neutropenia (>0.5 × 109/L) and thrombocytopenia (>50 × 109/L), but the count recovery criteria for CR are not met.
3 Duration of CR+CRh is defined as the time from first CR or CRh to the first documented relapse or death, whichever occurs first.
4 Duration of CR is defined as the time from first CR to the first documented relapse or death, whichever occurs first.
5 Duration of CRh is defined as the time from first CRh to the first documented relapse or death, whichever occurs first.
* The 95% CI of the response rate is derived using the exact method based on binomial distribution. The median of the response duration is derived using Kaplan-Meier method.
Abbreviations: ANC, absolute neutrophil count; CI, confidence interval; CR, complete remission; CRh, complete remission with partial hematologic recovery; DOCR, duration of CR; DOCRh, duration of CRh; NE, not estimable
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: REVUFORJ worked similarly in males and females.
- Race: REVUFORJ worked similarly in White, Unknown, Black, and Asian patients. The number of patients of other races was small; therefore, differences in how the drug worked could not be determined.
- Age: REVUFORJ worked similarly in patients younger and older than 65 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3. Efficacy Results (CR or CRh Rate) by Subgroup, Efficacy Population
Subgroup | REVUFORJ N=104 n/Ns (%) | 95% CI |
|---|---|---|
Sex |
|
|
Female | 15/67 (22.4) | 13.1, 34.2 |
Male | 7/37 (18.9) | 8.0, 35.2 |
Race |
|
|
White | 15/17 (20.0) | 11.6, 30.8 |
Black | 1/8 (12.5) | 0.3, 52.7 |
Asian | 4/10 (40) | 12.2, 73.8 |
Unknown | 2/10 (20) | 2.5, 55.6 |
Multiple | 0/1 (0) | 0.0, 97.5) |
Age group, years |
|
|
<17 | 7/25 (28.0) | 12.1, 49.4 |
17 to 65 | 10/67 (14.9) | 7.4, 25.7 |
>65 | 5/12 (41.7) | 15.2, 72.3 |
Source: Adapted from FDA Review
Note: Some values are not available, denoted by NA, due to the small number of responders in the specified category.
Abbreviations: CI, confidence interval; CR, complete remission; CRh, complete remission with partial hematologic recovery; N, number of patients in treatment arm; n, number of patients meeting criteria; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
What are the possible side effects?
The most common side effects of REVUFORJ are bleeding (hemorrhage), nausea and vomiting, muscle pain, infections (including bacterial and viral infections), low white blood cell counts with fever, diarrhea, changes in liver function tests, swelling in the arms and legs, decreased appetite, constipation, and tiredness.
REVUFORJ may cause serious side effects including:
- Differentiation syndrome, a serious, but common condition that affects blood cells, which may be life-threatening or lead to death if not treated. Signs and symptoms of differentiation syndrome include fever, cough, shortness of breath, severe headache, confusion, dizziness or lightheadedness, fast weight gain, swelling of arms, legs, neck, groin, or underarm area, and decreased urination.
- Changes in electrical activity of the heart (QT prolongation), that can cause irregular heartbeats that can be life-threatening or lead to death.
- REVUFORJ can cause harm to an unborn baby.
What are the possible side effects (results of trials used to assess safety)?
Table 4. Safety Results, Safety Population
Adverse Reaction | REVUFORJ, N=135 | |
|---|---|---|
All Grades % | Grade 3 or 4 % | |
Vascular disorders | ||
Hemorrhagea* | 53 | 9 |
Thrombosisb | 10 | 5 |
Gastrointestinal disorders | ||
Nauseac | 51 | 4 |
Diarrhead | 30 | 4 |
Constipation | 23 | 1 |
Musculoskeletal and connective tissue disorders | ||
Musculoskeletal paine | 42 | 6 |
Infections and infestations | ||
Infectionf | 41 | 29 |
Bacterial infectiong | 31 | 20 |
Viral infectionh | 23 | 4 |
Blood and lymphatic system disorders | ||
Febrile neutropenia | 35 | 33 |
Leukocytosis | 8 | 5 |
Neoplasms benign, malignant and unspecified (including cysts and polyps) | ||
Differentiation syndrome* | 29 | 13 |
Investigations | ||
Electrocardiogram QT prolonged | 29 | 12 |
Metabolism and nutrition disorders | ||
Decreased appetite | 24 | 8 |
General disorders and administration site conditions | ||
Edemai | 23 | 1 |
Fatiguej | 22 | 5 |
Source: REVUFORJ Prescribing Information
* Includes the following fatal adverse reactions: Differentiation syndrome (n=2); hemorrhage (n=1)
a Includes epistaxis, contusion, petechiae, gingival bleeding, haematuria, mouth hemorrhage, hematoma, hemoptysis, hemorrhoidal hemorrhage, subdural hematoma, vaginal hemorrhage, catheter site hemorrhage, conjunctival hemorrhage, ecchymosis, hemorrhage intracranial, anal hemorrhage, brain stem hemorrhage, eye hematoma, gastrointestinal hemorrhage, genital contusion, hematochezia, injection site hematoma, lower gastrointestinal hemorrhage, melena, mucosal hemorrhage, oral contusion, pulmonary, upper gastrointestinal hemorrhage, and vitreous hemorrhage.
b Includes disseminated intravascular coagulation, pulmonary embolism, cerebrovascular accident, deep vein thrombosis, embolism, hemorrhoids thrombosed, medical device site thrombosis, renal infarct, superficial vein thrombosis, thrombosis, and transient ischemic attack.
c Includes nausea and vomiting.
d Includes diarrhea, colitis, and neutropenic colitis.
e Includes back pain, arthralgia, pain in extremity, neck pain, myalgia, musculoskeletal chest pain, myositis, flank pain, musculoskeletal discomfort, and musculoskeletal pain.
f Includes sepsis, pneumonia, urinary tract infection, septic shock, sinusitis, upper respiratory tract infection, device related infection, skin infection, acute sinusitis, enterocolitis infectious, perirectal abscess, rectal abscess, rhinitis, abscess limb, appendicitis, bronchitis, conjunctivitis, endocarditis, epididymitis, eye infection, gastroenteritis, neutropenic sepsis, osteomyelitis, rash pustular, retinitis, shock, sialadenitis, tooth abscess, tooth infection, and vascular device infection.
g Includes bacteremia, cellulitis, clostridium difficile infection, staphylococcal bacteremia, paronychia, clostridium test positive, enterobacter infection, enterobacter sepsis, escherichia bacteremia, alpha haemolytic streptococcal infection, bacteriuria, cellulitis staphylococcal, enterobacter bacteremia, enterococcal bacteremia, enterococcal infection, escherichia urinary tract infection, folliculitis, klebsiella infection, klebsiella sepsis, lactobacillus bacteremia, and pseudomonal bacteremia.
h Includes COVID-19, rhinovirus infection, respiratory syncytial virus infection, cytomegalovirus infection reactivation, herpes simplex, herpes simplex reactivation, herpes zoster, COVID-19 pneumonia, coronavirus infection, cytomegalovirus infection, cytomegalovirus test positive, enterovirus infection, enterovirus test positive, Epstein-Barr virus infection, herpes simplex pharyngitis, herpes virus infection, norovirus infection, oral herpes, and pneumonia cytomegaloviral.
i Includes edema peripheral, generalised edema, edema, localized edema, and peripheral swelling.
j Includes fatigue and malaise.
Clinically relevant adverse reactions in less than 20% of patients who received REVUFORJ include:
- Cardiac disorders: Cardiac failure, pericardial effusion, ventricular tachycardia, and 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 and hyperkalemia
- Nervous system disorders: Taste disorder, syncope, headache, and paresthesia
- Renal disorders: Renal impairment
- Skin and subcutaneous disorders: Rash
Were there any differences in side effects among sex, race, and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: The occurrence of side effects was similar in White, Unknown, Black, and Asian patients. The number of patients of other races was small; therefore, differences in side effects could not be determined.
- Age: The occurrence of side effects was similar in patients 65 years and older. Compared to younger patients, the incidences of QTc prolongation and edema were higher in patients 65 and older.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 5. Side Effects by Subgroup, Safety Population
Subgroup | REVUFORJ N=135 n/Ns (%) |
|---|---|
Sex |
|
Female | 78/80 (97.5) |
Male | 55/55 (100) |
Race |
|
White | 88/90 (97.8) |
Black | 12/12 (100) |
Asian | 11/11 (100) |
Unknown | 19/19 (100) |
Multiple | 2/2 (100) |
Other | 1/1 (100) |
Age group, years |
|
<17 | 30/31 (96.8) |
17 to 65 | 89/90 (98.9) |
>65 | 14/14 (100) |
Source: Adapted from FDA Review
Abbreviations: N, number of patients in treatment arm; n, number of patients meeting criteria; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.