This is a Phase Ib/II, single arm, open label, multi-center study of siremadlin as monotherapy and in combination with DLI, in adult participants with AML who are in complete remission (CR) or CR with incomplete count recovery (CRi) post allo-SCT but are at high risk for relapse based on the presence of pre-transplant risk factors.~The primary purpose of the study is to confirm the safe dose and schedule of siremadlin monotherapy and in combination with DLI. The study is also designed to assess the preliminary efficacy in preventing hematologic relapse.~The study will enroll approximately 38 participants and will start with a dose confirmation of siremadlin monotherapy (Part 1) to determine the siremadlin recommended dose, followed by a treatment strategy of siremadlin/DLI (Part 2).~In part 1, approximately 12 participants will be enrolled in 2 cohorts (starting dose 30 mg/day on days 1-5 of a 28-day treatment cycle, dose level +1 at 40 mg/day and dose level -1 at 20 mg/day) and participants will be treated for a maximum of 24 cycles. In part 2, participants will follow a treatment strategy, which contains three consecutive phases for a maximum of 24 cycles in total:~A priming phase with siremadlin monotherapy at the recommended dose determined in Part 1 (for at least 2 cycles). Participants who are not eligible for the combination phase of siremadlin/DLI may continue priming phase with siremadlin monotherapy.~A combination phase of siremadlin in combination with DLI (siremadlin/DLI) for participants who are eligible to receive DLI (up to a total of 3 combination cycles).~A maintenance phase with siremadlin monotherapy.~Enrollment in part 2 will start after obtaining Health Authority's approval as applicable.~The decision of DLI administration in part 2 in eligible participants for combination will be at the discretion of the treating investigator per standard of practice/institutional guidelines.
The purpose of this study is to confirm a safe dose and schedule as well as the preliminary efficacy of siremadlin alone, and in combination with donor lymphocyte infusion (DLI), in adult participants with AML who are in remission following allogeneic stem cell transplantation (allo-SCT) but are at high risk for relapse based on the presence of pre-transplant risk factors.