Vadastuximab Talirine (SGN-CD33A; 33A) Combined With Azacitidine or Decitabine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia

Hypomethylating agents (HMAs), such as decitabine or azacitidine, are considered a standard
treatment for older patients with AML. The primary goals of this study are to test whether
patients treated with an HMA (either decitabine or azacitidine) in combination with 33A will
have better anti-tumor activity and/or survive longer than patients treated with an HMA in
combination with placebo.

Patients who meet eligibility criteria will be randomly assigned to one of two treatment
groups: 1) 33A plus HMA (Experimental Arm); or 2) placebo plus HMA (Comparator Arm). In
addition to evaluating survival and remission rates, the minimal residual disease
(MRD)-negative remission rate, duration of remission, event free- and leukemia-free survival,
and safety and tolerability will be compared between arms.

Inclusion Criteria:

- Newly diagnosed, previously untreated, cytologically/histologically confirmed de novo
or secondary AML according to World Health Organization (WHO) classification (except
for acute promyelocytic leukemia (APL))

- Intermediate or adverse cytogenetic risk

- Eligible for therapy with either decitabine or azacitidine

- Acceptable hematologic and organ function

Exclusion Criteria:

- AML associated with favorable risk karyotypes including inv(16), t(8;21), t(16;16), or
t(15;17)

- Patients who are candidates for allogeneic stem cell transplant at the time of
enrollment

- Patients with a history of one of the following myeloproliferative neoplasms:
essential thrombocythemia, polycythemia vera, and primary myelofibrosis

- Received prior treatment with HMA or chemotherapy for antecedent myelodysplastic
syndrome (MDS)