A Study to Investigate the Safety of Novel Dose Ramp-up Schedule(s) When Initiating Sonrotoclax in Participants Treated for Blood Cancers.

BeiGene

Status and phase: Begins enrollment this month; Phase 2; Phase 1

Conditions: CLL; Chronic Lymphocytic Leukemia

Treatments: Drug: Sonrotoclax; Drug: Zanubrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06697184

BGB-11417-108

Details and patient eligibility

About

The purpose of this study is to establish the safety of novel dosing and ramp-up schedules for sonrotoclax in participants with hematological malignancies.

Full description

This study will test the safety of novel sonrotoclax dosing with gradual increases of sonrotoclax dose over specified periods until the intended target daily dose is reached. The focus will be on tumor lysis syndrome (TLS) and related toxicity signals.

In the first part of the study, each ramp-up dosing schedule will first be tested in a small group of approximately 5 to 6 participants to assess safety and establish if the schedule is suitable for further testing in additional participants (schedule calibration). In the second part of the study, approved ramp-up schedules will be further assessed for safety in approximately 50 participants (schedule expansion).

Sonrotoclax is an experimental drug that works by blocking a protein called B-cell lymphoma-2 (BCL-2). This protein helps certain types of blood tumor cells to survive and grow. When sonrotoclax blocks Bcl-2 it slows down or stops the growth of tumor cells and helps them die. This can lead to improvements in patients with certain malignant diseases including Chronic Lymphocytic leukemia (CLL). The start of treatment by BCL2 inhibitor requires progressive ramp-up over the first weeks to avoid potential consequences of initial tumor cell breakage and the release of cell content in the bloodstream. Several ramp-up schedules have already been utilized so far, and this study aims to optimize the dosing schedule by evaluating novel ones as safe, while simpler and/or faster.

Zanubrutinib is a commercialized product 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 over 65 countries/regions worldwide for the treatment of adult participants with B cell malignancies, including CLL.

This study will take place at multiple centers worldwide. The overall time to participate in this study is approximately 17 months.

Enrollment: 56 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Stable ECOG Performance Status ≤ 2.
2. Adequate organ function and no very recent transfusion or blood growth factor
3. Participants of childbearing potential must be willing to use a highly effective method of birth control and refrain from egg donation for the duration of the study and for ≥ 90 days after the last dose of sonrotoclax or ≥ 30 days after the last dose of zanubrutinib, whichever is later.
4. Confirmed diagnosis of CLL, based on Hallek et al 2018, and requiring treatment due to certain features of their disease
5. At least 1 measurable lesion based on computed tomography (CT)/magnetic resonance imaging (MRI) and no history of prolymphocytic leukemia or Richter's transformation.

Exclusion criteria

1. Participants unable to comply with the requirements of the protocol
2. Serologic status reflecting active viral HBV or HCV infection
3. Positive HIV serology (HIVAb) status unless certain conditions are met.
4. Participants with any major surgical procedure ≤ 28 days before first dose of study treatment
5. Prior systemic treatment for the CLL
6. Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia requiring treatment

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

56 participants in 2 patient groups

Part 1: Schedule Calibration

Experimental group

Description:

Participants will receive zanubrutinib monotherapy with fixed duration, followed by combination sonrotoclax with zanubrutinib at protocol-defined ramp-up schedules until target daily dose will be reached.

Treatment:

Drug: Zanubrutinib

Drug: Sonrotoclax

Part 2: Schedule Expansion

Experimental group

Description:

Participants will receive zanubrutinib monotherapy with fixed duration, followed by combination sonrotoclax with zanubrutinib at ramp-up schedules as determined in Part 1.

Treatment:

Drug: Zanubrutinib

Drug: Sonrotoclax