Study of BMF-219, a Covalent Menin Inhibitor, in Adult Patients With AML, ALL (With KMT2A/ MLL1r, NPM1 Mutations), DLBCL, MM, and CLL/SLL

Inclusion Criteria:

• Age ≥ 18 years.

• All subjects must have histologically or pathologically confirmed diagnosis of theirmalignancy and/ or measurable R/ R disease, as follows:

1. Cohort 1 only: Refractory or relapsed acute leukemia defined as > 5% blasts inthe bone marrow or reappearance of blasts in the peripheral blood.

2. Cohort 2 only: Previously treated, pathologically confirmed de novo DLBCL, orDLBCL transformed from previously indolent lymphoma (e.g., follicular lymphoma)with documented clinical or radiological evidence of progressive or persistentdisease. At study entry, subjects must have measurable disease as per therevised criteria for response assessment of lymphoma.

3. Cohort 3 only: Measurable MM.

4. Cohort 4 only: Previously treated subjects with active CLL/SLL with meeting atleast 1 of the iwCLL 2018 criteria for requiring treatment.

• Subjects must be refractory or must have progressed on, or following discontinuationof the most recent anti-cancer therapy, with the following considerations:

1. Cohort 1 only: Have failed or are ineligible for any approved standard of caretherapies, including HSCT (Hematopoietic Stem Cell Transplantation).

2. Cohort 2 only: Must have received at least 2 previous systemic regimens for thetreatment of their de novo or transformed DLBCL.

3. Cohort 3 only: Must have received at least 3 anti-MM regimens includingproteasome inhibitor.

4. Cohort 4 only: Must have received at least 2 prior systemic treatment regimens.

• ECOG performance status of 0-2 and an estimated expected life expectancy of > 3months in the opinion of the Investigator.

• Adequate organ function.

• Both men and women of childbearing potential or their partners must use adequatebirth control measures during the course of the trial and for at least 90 days afterdiscontinuing study treatment.

Exclusion Criteria:

Subjects who meet any of the following criteria will not be enrolled in the study (all cohorts, unless otherwise indicated):

• Certain disease subtypes or occurrences, as follows:

1. Cohort 1: Acute promyelocytic leukemia (APL), chronic myeloid leukemia (CML) inblast crisis.

2. Cohort 2: Primary mediastinal B-cell lymphoma (PMBCL), DLBCL transformed fromdiseases other than indolent non-Hodgkin's Lymphoma (NHL).

3. Cohort 3: Active plasma cell leukemia, myeloma with amyloidosis, systemic lightchain amyloidosis.

4. Cohort 4: Known or suspected history of Richter's transformation.

• White Blood Count (WBC) > 50,000/μL (uncontrollable with cytoreductive therapy) (Cohort 1 only).

• Known central nervous involvement, as follows:

1. Cohort 1: Clinically active central nervous system (CNS) leukemia. Previouslycontrolled CNS leukemia is acceptable.

2. Cohort 2: Active CNS lymphoma or meningeal involvement.

3. Cohort 3: Active CNS MM.

4. Cohort 4: Active CNS leukemia.

• Prior menin inhibitor therapy.

• Known positive test for human immunodeficiency virus, hepatitis C, or hepatitis Bsurface antigen.

• Subjects with a pre-existing disorder predisposing them to a serious orlife-threatening infection.

• An active uncontrolled acute or chronic systemic fungal, bacterial, or viralinfection.