A Safety Study of SGN-CD33A in Combination With Standard-of-care in Patients With AML

A Phase 1b Dose-escalation Study of SGN-CD33A in Combination With Standard-of-care for Patients With Newly Diagnosed Acute Myeloid Leukemia

This study will examine the safety profile of vadastuximab talirine (SGN-CD33A) by itself (monotherapy) or in combination with other standard treatments. The main purpose of this study is to find the best dose and schedule for SGN-CD33A when given in combination with standard induction treatment, in combination with standard consolidation treatment, or by itself for maintenance treatment. This will be determined by observing the dose-limiting toxicities (the side effects that prevent further increases in dose) of SGN-CD33A. In addition, the pharmacokinetic profile and anti-leukemic activity of the study treatment will be assessed.

The study will be conducted in the following distinct parts:

Part A: Induction dose escalation - 7+3 combined with SGN-CD33A (Day 1 and Day 4 dosing)

Part B: Consolidation dose escalation - consolidation combined with SGN-CD33A; up to 4 cycles of consolidation therapy will be administered after SGN-CD33A (Day 1 of each cycle).

Part C: Maintenance - SGN-CD33A Monotherapy; Up to 24 patients with and up to 24 patient without prior allogeneic stem cell transplant will be treated with SGN-CD33A. Both arms will enroll simultaneously. SGN-CD33A will be administered on Day 1 of each 6-week cycle for up to 8 cycles.

Part D: Induction plus consolidation - induction/consolidation combined with SGN-CD33A; patients who achieve a CR/CRi (with or without a second induction) will receive up to 4 cycles of consolidation therapy administered after SGN-CD33A (Day 1 of each cycle).

Part E: Induction dose escalation - 7+3 combined with SGN-CD33A (Day 1 dosing)

Inclusion Criteria:

• All subtypes of Acute Myeloid leukemia (except for acute promyelocytic leukemia)
• Eastern Cooperative Oncology Group status of 0 or 1
• Adequate baseline renal and hepatic function
• Central venous access
• Part specific requirements: eligible to receive induction; achieved CR/CRi with standard induction and eligible to receive consolidation; in CR with documented blood count recovery for maintenance

Exclusion Criteria:

• Previous treatment for MDS or MPN for dose escalation cohorts
• Inadequate lung function
• Inadequate heart function