Summary
This study will test the safety of new ways of administering a targeted medicine called sonrotoclax, with gradual increases in the dose over specified periods until the intended target daily dose is reached. The study will have two parts.
In the first part of the study (schedule calibration), each ramp-up dosing schedule will first be tested in a small group of 5-6 participants to assess safety, and establish if the schedule is suitable for further testing in additional participants. During this part of the study, participants will receive zanubrutinib by itself for a fixed period of time, followed by combination treatment with sonrotoclax and zanubrutinib at a study-defined ramp-up schedules until target daily dose will be recahed.
In the second part of the study (schedule expansion), approved ramp-up schedules will be further assessed for safety in approximately 50 participants. During this part, participants will receive zanubrutinin by itself for a fixed period of time, followed by combination treatment with sonrotoclax and zanubrutinib at ramp-up schedules as determined in Part 1.
About the study medicines
Sonrotoclax is an experimental drug that works by blocking a proteiin called B-cell lymphoma-2 (BCL-2). This protien helps certain types of blood tumour cells to survive and grow. When sonrotoclax blocks BCL-2 it slows down or stops the growth of tumour cells and helps them die. This can lead to improvements in patients with certain malignant diseases including Chronic Lymphocytic Leukaemia (CLL). The start of treatment by BCL-2 inhibitor requires progressive ramp-up over the first weeks to avoid potential consequences of initial tumour cell breakage and the release of cell content in the bloodstream. Several ramp-up schedules have already been used so far, and this study aims to optimise the dosing schedule by evaluating new schedules as safe, while simpler and/or faster.
Zanubrutinib is a product already available for treatment that works by blocking a protein called Bruton's tyrosine kinase (BTK) and controlling the activity and survival of malignant B-cells. Zanubrutinib has received approval in many countries for the treatment of people with B-cell malignancies, including CLL.
Both sonrotoclax and zanubrutinib are both administred orally.