Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as 14C-bleximenib, JNJ-75276617
Bleximenib · 4 trials · 5 indications
CR is defined as Bone marrow blasts less than (\<) 5 percent (%); Absence of circulating blasts; Absence of extramedullary disease; Absolute neutrophil count (ANC) greater than or equal to (\>=) 1.0 \* 10\^9/Liter (1,000/microliter \[mcL\]); Platelet count \>= 100 \* 10\^9/L (100,000/mcL).
Overall survival time is defined as the time duration from the date of randomization to death due to any cause.
Total amount excreted into the urine, expressed as a percentage of the administered dose will be reported.
Total amount excreted into the feces expressed as a percentage of the administered dose will be reported.
Aeu defined as the total amount of bleximenib and radioactivity excreted into the urine will be reported.
Aef defined as the total amount of bleximenib and radioactivity excreted into the feces will be reported.
AUC0-t in whole blood and plasma will be reported.
Maximum observed concentration in whole blood and plasma will be determined.
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Number of Participants with AEs by severity will be reported. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Number of participants with DLT will be reported according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Percentage of participants with DLT will be assessed accordingly to national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 5.
Rate of CR/CRh is defined as the percentage of participants achieving a CR or CRh at any time post-treatment.
| Arm | Type | Description |
|---|---|---|
| Arm A: Bleximenib and Venetoclax (VEN) + Azacitidine (AZA) | EXPERIMENTAL | Participants with acute myeloid leukemia (AML) will receive bleximenib in combination with venetoclax (VEN) and azacitidine (AZA) for 28-days treatment cycles and treatment will continue until progression or unacceptable toxicity. |
| Arm B: Placebo and Venetoclax (VEN) + Azacitidine (AZA) | PLACEBO_COMPARATOR | Participants with AML will receive placebo in combination with VEN and AZA for 28-days treatment cycles, and treatment will continue until progression or unacceptable toxicity. |
| Bleximenib | EXPERIMENTAL | Participants will receive a single oral dose of 14C-bleximenib on Cycle 1 Day 1. The recommended Phase 2 dose (RP2D) of bleximenib will start on Cycle 1 Day 2 with non-radiolabeled bleximenib and will continue until the end of Cycle 1 (cycle duration=28 days), with subsequent roll-over for eligible participants to 75276617ALE1001 (NCT04811560) for continued non-radiolabeled bleximenib administration as appropriate. |
| Arm A: Relapsed/Refractory Setting | EXPERIMENTAL | Participants with relapsed/refractory AML harboring NPM1, KMT2A, NUP98, or NUP214 alterations will receive bleximenib in combination with either venetoclax (VEN) (Cohort A1: bleximenib+VEN) or azacitidine (AZA) (Cohort A2: bleximenib +AZA) or VEN+AZA (Cohort A3: bleximenib+VEN+AZA) or VEN + AZA (Cohort A4: bleximenib + VEN + AZA) in adolescent participants aged greater than or equal to (\>=) 12 years and less than (\<) 18 years of age, to select the recommended phase 2 dose (RP2D) of bleximenib in combination with VEN, AZA or VEN+AZA (dose selection). In dose expansion portion of the study, participants will receive bleximenib in combination with AML directed therapies at the RP2D(s). |
| Arm B: Newly Diagnosed Chemotherapy Ineligible Setting | EXPERIMENTAL | Participants will receive bleximenib in combination with VEN+AZA as frontline chemo therapy for newly diagnosed AML participants harboring KMT2A, NPM1, NUP98, or NUP214 alterations who are \>=75 years of age or \>=18 years of age to \<75 years of age with comorbidities that preclude the use of intensive induction chemotherapy. |
| Arm C: Newly Diagnosed Chemotherapy Eligible Setting | EXPERIMENTAL | Participants will receive combination of bleximenib with cytarabine+daunorubicin or idarubicin chemotherapy as frontline treatment regimen for participants \>= 18 to \<75 years of age with AML harboring NPM1, KMT2A, NUP98, or NUP214 alterations and eligible for intensive chemotherapy. |
| Name | Type | Description |
|---|---|---|
| Bleximenib | DRUG | Bleximenib will be administered orally. |
| Venetoclax (VEN) | DRUG | VEN will be administered orally. |
| Azacitidine (AZA) | DRUG | AZA will be administered intravenously or subcutaneously. |
| Placebo | DRUG | Placebo will be administered orally. |
| 14C-bleximenib | DRUG | 14C-bleximenib will be administered orally. |
| Cytarabine | DRUG | Participants will receive cytarabine. |
| Daunorubicin or Idarubicin | DRUG | Participants will receive daunorubicin or idarubicin. |
Inclusion criteria: * Be 18 years of age or older at the time of informed consent * Previously untreated lysine N-methyltransferase 2A gene rearranged (KMT2Ar) or nucleophosmin 1 gene mutated (NPM1m) acute myeloid leukemia (AML) with greater than or equal to (\> or =) 10% bone marrow blasts per 202...
Bleximenib is an investigational oral therapy being studied for acute leukemias, including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). It is being evaluated both as a single agent and in combinations, including with venetoclax and azacitidine in newly diagnosed AML. It is not yet approved for any indication.
Bleximenib targets the menin/KMT2A interaction. Menin is a scaffold protein that binds KMT2A (formerly MLL) fusion proteins and drives leukemogenic gene expression in certain acute leukemias. Bleximenib is a small molecule designed to disrupt that protein-protein interaction. It is classified within the -nib (kinase inhibitor) naming family.
Bleximenib is being developed by Johnson & Johnson, which trades on the New York Stock Exchange under the ticker JNJ. The company is running the clinical program across multiple countries, including the United States, Europe, Asia, Australia, and Latin America.
Bleximenib is in clinical development and has not been approved by the FDA. Its program spans Phase 1 through Phase 3. A Phase 3 trial in newly diagnosed acute myeloid leukemia is currently recruiting, while earlier-phase studies in acute leukemia are ongoing or have been completed.
Bleximenib is being studied in several trials. NCT06852222 is a Phase 3 study combining bleximenib with venetoclax and azacitidine in newly diagnosed AML. NCT04811560 is a Phase 1/2 study in acute leukemia (cAMeLot-1). NCT05453903 is a Phase 1 study in combination with AML-directed therapies, and NCT07295951 evaluated radiolabeled 14C-bleximenib.
14C-bleximenib is a radiolabeled form of bleximenib used in a completed Phase 1 study (NCT07295951) in participants with acute leukemia in the United Kingdom. It contains a carbon-14 label to allow researchers to track how the drug is absorbed, distributed, metabolized, and excreted in the body.