DFP-10917 in Combination With Venetoclax in Relapsed or Refractory Acute Myeloid Leukemia

Inclusion Criteria:

• Signed informed consent and ability to comply with protocol requirements.

• Histologically or pathologically confirmed diagnosis of acute myeloid leukemia basedon World Health Organization classification that has relapsed after, or isrefractory to, up to 2 prior induction regimens that may have included intensivechemotherapy (e.g., "7+3" cytarabine and daunorubicin), epigenetic therapy (i.e.,azacitidine or decitabine with/without venetoclax), or targeted therapy (e.g.,FLT-3, IDH 1/2, BCL-2, monoclonal antibody).

(Relapse is defined as reemergence of ≥5% leukemia blasts in bone marrow or ≥1% blasts in peripheral blood 90 days to 24 months after first complete remission or complete remission with incomplete hematologic recovery. Refractory acute myeloid leukemia is defined as persistent disease ≥28 days after initiation of intensive induction therapy (up to 2 induction cycles) or relapse <90 days after first complete remission or complete remission with incomplete hematologic recover. Refractory disease for patients undergoing hypomethylating agent induction is defined as lack of remission following at least 2 cycles of epigenetic therapy without reduction in bone marrow blast status).

• Adequate organ function as defined by the following laboratory values:

• Creatinine clearance >30 mL/min (by Cockcroft-Gault method),

• Total serum bilirubin <1.5 × upper limit of normal unless due to Gilbert'ssyndrome, leukemic organ involvement, hemolysis or considered an effect ofregular blood transfusions,

• Alanine aminotransferase and aspartate aminotransferase <3 × upper limit ofnormal, unless due to leukemic organ involvement.

• Eastern Cooperative Oncology Group performance status of 0, 1, or 2).

• Projected life expectancy of ≥12 weeks.

• Female patients of childbearing potential must:

• Have a negative serum or urine pregnancy test prior to study treatmentinitiation.

• Agree to use at least 1 highly effective form of contraception during studytreatment and for 3 months after the last dose.

• Male patients with female partners of childbearing potential must -- Agree to use atleast 1 highly effective form of contraception during study treatment and for atleast 3 months after the last dose.

Exclusion Criteria:

• Any >Grade 1 persistent clinically significant toxicities from prior chemotherapy.

• Leukemic blast count >25 × 109/L. Hydroxyurea permitted to control leukocytosis.

• Known history of human immunodeficiency virus or active hepatitis B or activehepatitis C infection.

• Concomitant malignancies for which patients are receiving active therapy at the timeof signing consent. Patients with adequately treated basal or squamous cellcarcinoma of the skin, adequately treated carcinoma in situ (e.g., cervix), breastcancer receiving adjuvant endocrine therapy or prostate cancer not under activesystemic treatment other than hormonal therapy may enroll irrespective of the timeof diagnosis, with Medical Monitor approval.

• Known active central nervous system involvement by leukemia. Patients withpreviously diagnosed central nervous system leukemia are eligible if the centralnervous system leukemia is under control and intrathecal treatment may continuethroughout the study.

• Diagnosis of acute promyelocytic leukemia.

• Prior exposure to anticancer therapies including chemotherapy, radiotherapy or otherinvestigational therapy, including targeted small molecule agents within 14 days ofthe first day of study treatment or within 5 half-lives prior to first dose of studytreatment. Note that hydroxyurea up to 5 g daily × 3 days is permitted to reduceelevated white blood cell (WBC) count.

• Venetoclax exposure in more than 1 prior regimen.

• Prior exposure to biologic agents (e.g., monoclonal antibodies) for anti-neoplasticintent within 14 days prior to first dose of study drug.

• Prior hematopoietic stem cell transplantation.

• Malabsorption syndrome or other condition that precludes enteral route ofadministration.

• Pregnancy or lactation.

• Active uncontrolled systemic infection (viral, bacterial, or fungal).

• Ongoing treatment with strong or moderate CYP3A inhibitors or CYP3A inducers, P-gpinhibitors, or narrow therapeutic index P-gp substrates that cannot be discontinuedat least 1 week prior to start of venetoclax dosing excluding antifungalprophylaxis.