Study of HDM201 in combination with MBG453 or Venetoclax in acute myeloid leukemia or myelodysplastic syndrome

Summary description of the study

This is an international study. Approximately 80 patients worldwide will participate in this study and will be divided into two groups: 40 patients will receive the combination of HDM201 and MBG453 and the other 40 will receive the combination of HDM201 and Venetoclax. The purpose of this study is to determine the dose strengths and administration schedules of HDM201+MBG453 (Group 1) and HDM201+Venetoclax (Group 2) that can be administered safely, and to find out if the combinations show a potential benefit in patients with AML or MDS. HDM201 is a drug that restores the normal function of a protein p53, leading to slower growth of tumor cells or possibly their death. MBG453 is an antibody that blocks a protein called TIM-3 and may thereby enhance the activity of certain immune cells (T-lymphocytes) to attack your cancer. Venetoclax is a drug that inhibits a protein called Bcl-2, leading to slower growth of tumor cells or possibly their death. Study visits are divided into cycles. Each cycle lasts 4 weeks (28 days). Participation in the study includes hospital or clinic stays, physical examinations, and the collection of blood and other samples. In the first cycle, patients must come to the study doctor's clinic 9 times, 8 times in Cycle 2, 4 times in Cycle 3, and 3 times from Cycle 4 until the study treatment is completed. The duration of visits depends on the planned examinations. The duration of the treatment phase is variable, as each patient may respond differently to the study treatment. After treatment ends, there will be further follow-up examinations for safety and possibly until disease progression.

(BASEC)

Intervention under investigation

Each group of 40 patients will receive either the combination of HDM201 and MBG453 or HDM201 and Venetoclax.

Patients assigned to the combination group HDM201+MBG453 will take HDM201 for the first 5 days of each cycle. Each cycle lasts 28 days. MBG453 will be administered either on days 1 and 15 of each cycle or only on day 1 of each cycle.

Patients in the combination group HDM201+Venetoclax will take HDM201 for the first 5 days of each cycle. In the first 4 to 5 days of Cycle 1, escalating doses of Venetoclax will be administered and then a fixed daily dose will be continued.

(BASEC)

Disease under investigation

Patients with one of the following blood cancers may participate in this study: acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

(BASEC)

Sponsor

Novartis Pharma Schweiz AG

(BASEC)

Name of the authorising ethics committee (for multicentre studies, only the lead committee)

Ethics Committee northwest/central Switzerland EKNZ

(BASEC)

Date of authorisation

23.08.2019

(BASEC)

Results of the trial