Komzifti
Generic: ZIFTOMENIB
Basic Information
Manufacturer
Kura Oncology, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
b650f696-3391-4274-8b55-a5f5e9d04769
Indications & Usage
1 INDICATIONS AND USAGE KOMZIFTI is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 ( NPM1 ) mutation who have no satisfactory alternative treatment options [see Dosage and Administration ( 2.1 ), Clinical Pharmacology ( 12.1 ), and Clinical Studies ( 14 )] .
KOMZIFTI is a menin inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 ( NPM1 ) mutation who have no satisfactory alternative treatment options.
( 1 )
KOMZIFTI is a menin inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 ( NPM1 ) mutation who have no satisfactory alternative treatment options.
( 1 )
Adverse Reactions
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 [see Warnings and Precautions ( 5.2 )] The most common adverse reactions (≥20%) are infection without an identified pathogen, hemorrhage, diarrhea, nausea, fatigue, edema, bacterial infection, musculoskeletal pain, differentiation syndrome, pruritus, febrile neutropenia, and transaminases increased.
( 6.1 ) The most common laboratory abnormalities (≥10%) are aspartate aminotransferase increased, potassium decreased, albumin decreased, alanine aminotransferase increased, sodium decreased, creatinine increased, alkaline phosphatase increased, bilirubin increased, potassium increased.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Kura Oncology, Inc., at 1-844-KURAONC, 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.
Relapsed or Refractory AML with an NPM1 Mutation The safety of KOMZIFTI for the treatment of patients with relapsed or refractory AML with an NPM1 mutation was evaluated in KO-MEN-001 [see Clinical Studies ( 14 )] .
Patients received KOMZIFTI 600 mg once daily (n=112).
The median duration of exposure to KOMZIFTI was 2.2 months (range 0.1 to 21.5 months).
Fatal adverse reactions occurred in 4 (4%) patients who received KOMZIFTI, including 2 with differentiation syndrome, 1 with infection, and 1 with sudden death.
Serious adverse reactions were reported in 79% of patients who received KOMZIFTI.
Serious adverse reactions occurring in ≥ 5% of patients included infection without an identified pathogen (29%), febrile neutropenia (18%), bacterial infection (16%), differentiation syndrome (16%), and dyspnea (6%).
Dosage interruption of KOMZIFTI due to an adverse reaction occurred in 54% of patients.
Adverse reactions that required dose interruption in ≥ 2% of patients included infection without an identified pathogen (15%), differentiation syndrome (13%), febrile neutropenia (5%), pyrexia (4%), electrocardiogram QT prolonged (4%), leukocytosis (4%), bacterial infection (3%), cardiac failure (2%), cholecystitis (2%), diarrhea (2%), pruritus (2%), and thrombosis (2%).
Dose reduction of KOMZIFTI due to an adverse reaction occurred in 4% of patients.
Permanent discontinuation of KOMZIFTI due to an adverse reaction occurred in 21% of patients.
Adverse reactions that required permanent discontinuation of KOMZIFTI in ≥ 2% of patients were infection without an identified pathogen (8%), bacterial infection (4%), cardiac arrest (2%), and differentiation syndrome (2%).
The most common (≥ 20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased, infection without an identified pathogen, potassium decreased, albumin decreased, alanine aminotransferase increased, sodium decreased, creatinine increased, alkaline phosphatase increased, hemorrhage, diarrhea, nausea, fatigue, edema, bacterial infection, musculoskeletal pain, bilirubin increased, potassium increased, differentiation syndrome, pruritus, febrile neutropenia, and transaminases increased.
Table 3 summarizes the adverse reactions in KO-MEN-001.
Table 3 Adverse Reactions Reported in ≥20% (Any Grade) or ≥5% (Grade 3 or 4) of Patients with Relapsed or Refractory AML †Includes the following fatal adverse reactions: infection (n=1) and differentiation syndrome (n=2).
*No Grade 4 events were reported for this adverse reaction.
a Includes abdominal abscess, abscess limb, anal abscess, anorectal infection, bronchitis, conjunctivitis, device related infection, device related sepsis, diverticulitis, emphysematous cystitis, enterocolitis infectious, gingivitis, hordeolum, infection, large intestine infection, nail infection, necrotizing fasciitis, penile infection, periodontitis, perirectal abscess, peritonitis, pneumonia, postoperative abscess, respiratory tract infection, rhinitis, sepsis, septic shock, sinusitis, skin infection, soft tissue infection, tooth infection, upper respiratory tract infection, urosepsis, vaginal infection, vascular device infection, wound infection.
b Includes bacteremia, bacterial infection, bacterial pyelonephritis, breast cellulitis, cellulitis, clostridial infection, clostridium difficile colitis, clostridium difficile infection, enterobacter sepsis, enterococcal bacteremia, erysipelas, escherichia bacteremia, escherichia infection, escherichia sepsis, escherichia urinary tract infection, klebsiella bacteremia, klebsiella infection, klebsiella urinary tract infection, paronychia, pneumonia bacterial, pneumonia klebsiella, pseudomonal bacteremia, staphylococcal bacteremia.
c Includes adenovirus infection, COVID-19, genital herpes, herpes simplex reactivation, herpes virus infection, herpes zoster, nasal herpes, oral herpes, pneumonia influenzas, pneumonia parainfluenza viral, respiratory syncytial virus infection, rhinovirus infection.
d Includes angina bullosa hemorrhagic, bladder tamponade, catheter site hematoma, conjunctival hemorrhage, contusion, disseminated intravascular coagulation, ecchymosis, epistaxis, gastric hemorrhage, gastrointestinal hemorrhage, gingival bleeding, hematemesis, hematochezia, hematoma, hematuria, hemoptysis, hemorrhage, hemorrhoidal hemorrhage, hyperfibrinolysis, injection site hematoma, injection site hemorrhage, lower gastrointestinal hemorrhage, melaena, mouth hemorrhage, oral blood blister, petechiae, purpura, rectal hemorrhage, retinal hemorrhage, shock hemorrhagic, skin hemorrhage, subdural hematoma, tongue hemorrhage, traumatic hematoma, upper gastrointestinal hemorrhage, vaginal hemorrhage, vitreous hemorrhage.
e Includes diarrhea, colitis, colitis erosive.
f Includes nausea, vomiting.
g Includes fatigue, asthenia, malaise.
h Includes edema, edema peripheral, generalized edema, localized edema, peripheral swelling.
i Includes arthralgia, back pain, bone pain, flank pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, pain in extremity.
j Includes pruritus, nasal pruritus.
k Includes white blood cell count increased, leukocytosis, hyperleukocytosis.
l Includes transaminases increased, alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyl transferase increased, hypertransaminasemia.
m Includes renal impairment: acute kidney injury, azotemia, blood creatinine increased, blood urea increased, chronic kidney disease, postrenal failure, renal failure.
Adverse Reaction KOMZIFTI N=112 All Grades † (%) Grade 3 or 4 (%) Infections and infestations Infection without identified pathogen a 52 38 Bacterial infection b 28 17 Viral infection c 16 5 Vascular disorders Hemorrhage d 38 8 Hypertension 11 5 Gastrointestinal disorders Diarrhea e* 36 5 Nausea f* 35 2 General disorders and administration site conditions Fatigue g 34 8 Edema h* 30 3 Musculoskeletal and connective tissue disorders Musculoskeletal pain i 28 4 Neoplasms benign, malignant, and unspecified (incl cysts and polyps) Differentiation syndrome 26 13 Skin and subcutaneous Pruritus j* 23 0 Blood and lymphatic system disorder Febrile neutropenia 22 22 Leukocytosis k* 16 5 Investigations Transaminases increased l 21 8 Electrocardiogram QT prolonged * 12 8 Renal and urinary disorders Renal impairment m 19 6 Respiratory, thoracic, and mediastinal disorders Hypoxia 9 5 Table 4 summarizes the laboratory abnormalities in KO-MEN-001.
Table 4 Selected New or Worsening Laboratory Abnormalities in Patients with Relapsed or Refractory AML *The denominator used to calculate the rate varied from 108 to 110 based on the number of patients with a baseline value and at least one post-baseline value.
Laboratory Abnormality KOMZIFTI Grades 1-4* (%) Grade 3-4* (%) Aspartate aminotransferase increased 53 4 Potassium decreased 52 22 Albumin decreased 51 5 Alanine aminotransferase increased 50 6 Sodium decreased 49 3 Creatinine increased 45 4 Alkaline phosphatase increased 41 5 Bilirubin increased 27 6 Potassium increased 26 6
( 6.1 ) The most common laboratory abnormalities (≥10%) are aspartate aminotransferase increased, potassium decreased, albumin decreased, alanine aminotransferase increased, sodium decreased, creatinine increased, alkaline phosphatase increased, bilirubin increased, potassium increased.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Kura Oncology, Inc., at 1-844-KURAONC, 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.
Relapsed or Refractory AML with an NPM1 Mutation The safety of KOMZIFTI for the treatment of patients with relapsed or refractory AML with an NPM1 mutation was evaluated in KO-MEN-001 [see Clinical Studies ( 14 )] .
Patients received KOMZIFTI 600 mg once daily (n=112).
The median duration of exposure to KOMZIFTI was 2.2 months (range 0.1 to 21.5 months).
Fatal adverse reactions occurred in 4 (4%) patients who received KOMZIFTI, including 2 with differentiation syndrome, 1 with infection, and 1 with sudden death.
Serious adverse reactions were reported in 79% of patients who received KOMZIFTI.
Serious adverse reactions occurring in ≥ 5% of patients included infection without an identified pathogen (29%), febrile neutropenia (18%), bacterial infection (16%), differentiation syndrome (16%), and dyspnea (6%).
Dosage interruption of KOMZIFTI due to an adverse reaction occurred in 54% of patients.
Adverse reactions that required dose interruption in ≥ 2% of patients included infection without an identified pathogen (15%), differentiation syndrome (13%), febrile neutropenia (5%), pyrexia (4%), electrocardiogram QT prolonged (4%), leukocytosis (4%), bacterial infection (3%), cardiac failure (2%), cholecystitis (2%), diarrhea (2%), pruritus (2%), and thrombosis (2%).
Dose reduction of KOMZIFTI due to an adverse reaction occurred in 4% of patients.
Permanent discontinuation of KOMZIFTI due to an adverse reaction occurred in 21% of patients.
Adverse reactions that required permanent discontinuation of KOMZIFTI in ≥ 2% of patients were infection without an identified pathogen (8%), bacterial infection (4%), cardiac arrest (2%), and differentiation syndrome (2%).
The most common (≥ 20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased, infection without an identified pathogen, potassium decreased, albumin decreased, alanine aminotransferase increased, sodium decreased, creatinine increased, alkaline phosphatase increased, hemorrhage, diarrhea, nausea, fatigue, edema, bacterial infection, musculoskeletal pain, bilirubin increased, potassium increased, differentiation syndrome, pruritus, febrile neutropenia, and transaminases increased.
Table 3 summarizes the adverse reactions in KO-MEN-001.
Table 3 Adverse Reactions Reported in ≥20% (Any Grade) or ≥5% (Grade 3 or 4) of Patients with Relapsed or Refractory AML †Includes the following fatal adverse reactions: infection (n=1) and differentiation syndrome (n=2).
*No Grade 4 events were reported for this adverse reaction.
a Includes abdominal abscess, abscess limb, anal abscess, anorectal infection, bronchitis, conjunctivitis, device related infection, device related sepsis, diverticulitis, emphysematous cystitis, enterocolitis infectious, gingivitis, hordeolum, infection, large intestine infection, nail infection, necrotizing fasciitis, penile infection, periodontitis, perirectal abscess, peritonitis, pneumonia, postoperative abscess, respiratory tract infection, rhinitis, sepsis, septic shock, sinusitis, skin infection, soft tissue infection, tooth infection, upper respiratory tract infection, urosepsis, vaginal infection, vascular device infection, wound infection.
b Includes bacteremia, bacterial infection, bacterial pyelonephritis, breast cellulitis, cellulitis, clostridial infection, clostridium difficile colitis, clostridium difficile infection, enterobacter sepsis, enterococcal bacteremia, erysipelas, escherichia bacteremia, escherichia infection, escherichia sepsis, escherichia urinary tract infection, klebsiella bacteremia, klebsiella infection, klebsiella urinary tract infection, paronychia, pneumonia bacterial, pneumonia klebsiella, pseudomonal bacteremia, staphylococcal bacteremia.
c Includes adenovirus infection, COVID-19, genital herpes, herpes simplex reactivation, herpes virus infection, herpes zoster, nasal herpes, oral herpes, pneumonia influenzas, pneumonia parainfluenza viral, respiratory syncytial virus infection, rhinovirus infection.
d Includes angina bullosa hemorrhagic, bladder tamponade, catheter site hematoma, conjunctival hemorrhage, contusion, disseminated intravascular coagulation, ecchymosis, epistaxis, gastric hemorrhage, gastrointestinal hemorrhage, gingival bleeding, hematemesis, hematochezia, hematoma, hematuria, hemoptysis, hemorrhage, hemorrhoidal hemorrhage, hyperfibrinolysis, injection site hematoma, injection site hemorrhage, lower gastrointestinal hemorrhage, melaena, mouth hemorrhage, oral blood blister, petechiae, purpura, rectal hemorrhage, retinal hemorrhage, shock hemorrhagic, skin hemorrhage, subdural hematoma, tongue hemorrhage, traumatic hematoma, upper gastrointestinal hemorrhage, vaginal hemorrhage, vitreous hemorrhage.
e Includes diarrhea, colitis, colitis erosive.
f Includes nausea, vomiting.
g Includes fatigue, asthenia, malaise.
h Includes edema, edema peripheral, generalized edema, localized edema, peripheral swelling.
i Includes arthralgia, back pain, bone pain, flank pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, pain in extremity.
j Includes pruritus, nasal pruritus.
k Includes white blood cell count increased, leukocytosis, hyperleukocytosis.
l Includes transaminases increased, alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyl transferase increased, hypertransaminasemia.
m Includes renal impairment: acute kidney injury, azotemia, blood creatinine increased, blood urea increased, chronic kidney disease, postrenal failure, renal failure.
Adverse Reaction KOMZIFTI N=112 All Grades † (%) Grade 3 or 4 (%) Infections and infestations Infection without identified pathogen a 52 38 Bacterial infection b 28 17 Viral infection c 16 5 Vascular disorders Hemorrhage d 38 8 Hypertension 11 5 Gastrointestinal disorders Diarrhea e* 36 5 Nausea f* 35 2 General disorders and administration site conditions Fatigue g 34 8 Edema h* 30 3 Musculoskeletal and connective tissue disorders Musculoskeletal pain i 28 4 Neoplasms benign, malignant, and unspecified (incl cysts and polyps) Differentiation syndrome 26 13 Skin and subcutaneous Pruritus j* 23 0 Blood and lymphatic system disorder Febrile neutropenia 22 22 Leukocytosis k* 16 5 Investigations Transaminases increased l 21 8 Electrocardiogram QT prolonged * 12 8 Renal and urinary disorders Renal impairment m 19 6 Respiratory, thoracic, and mediastinal disorders Hypoxia 9 5 Table 4 summarizes the laboratory abnormalities in KO-MEN-001.
Table 4 Selected New or Worsening Laboratory Abnormalities in Patients with Relapsed or Refractory AML *The denominator used to calculate the rate varied from 108 to 110 based on the number of patients with a baseline value and at least one post-baseline value.
Laboratory Abnormality KOMZIFTI Grades 1-4* (%) Grade 3-4* (%) Aspartate aminotransferase increased 53 4 Potassium decreased 52 22 Albumin decreased 51 5 Alanine aminotransferase increased 50 6 Sodium decreased 49 3 Creatinine increased 45 4 Alkaline phosphatase increased 41 5 Bilirubin increased 27 6 Potassium increased 26 6