A Study of Siremadlin in Combination With Venetoclax Plus Azacitidine in Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Chemotherapy.

The recommended dose of siremadlin in combination with venetoclax plus azacitidine was to be determined to be explored further in the expansion phase and the preliminary efficacy in achieving Complete Remission (CR) evaluated in participants who responded sub-optimally to first-line venetoclax plus azacitidine treatment. The study was planned to be conducted in two parts. The primary purpose of Part 1 (Safety Run- in) was to rule out excessive toxicity of siremadlin when administered in combination with venetoclax plus azacitidine while the primary purpose of Part 2 (Expansion) was to evaluate the preliminary efficacy of siremadlin when combined with venetoclax plus azacitidine in the respective patient population. The study treatment (siremadlin in combination with venetoclax plus azacitidine) was administered in cycles with a planned duration of 28 days for each cycle and would continue until the participants experienced disease progression/relapse or unacceptable toxicity. The initial enrollment plan and safety review was as follow: * In the Safety run-in part, 9-15 participants were planned to be enrolled in each arm. Approximately 3-6 participants were planned to be enrolled at the starting dose level of siremadlin in combination with venetoclax plus azacitidine in both arms independently. Provided the starting dose level was determined to be safe, approximately 6-9 additional participants were planned to be enrolled at dose level +1. Safety review meetings were planned to take place involving participating investigators and the Sponsor Team to make decisions regarding siremadlin dose and determine the recommended dose for expansion. * Approximately 26 patients were planned to be treated at the recommended dose in the expansion part. In the safety run-(Part 1) 10 sites in 7 countries enrolled 14 patients. After enrolling 14 patients (6 patients in Arm 1 and 8 patients in Arm 2), Novartis took the decision to put the enrollment in permanent halt and terminate the siremadlin program. For that reason, the enrollment in Part 2 (expansion phase) did not open. The Novartis decision was not driven by any safety concerns.