What Is Sonrotoclax?
Sonrotoclax is an investigational drug currently being studied in clinical trials. It is administered orally, often as part of a combination therapy. While the specific mechanism of action is not detailed in the available trial information, studies are exploring its safety and effectiveness, particularly in various blood cancers.
Sonrotoclax is being investigated for the treatment of several conditions, including Chronic Lymphocytic Leukemia (CLL), Mantle Cell Lymphoma (MCL), and Acute Myeloid Leukemia (AML). It is frequently studied in combination with other therapies, such as zanubrutinib, obinutuzumab, or rituximab, to evaluate potential synergistic effects.
There are currently 24 clinical trials involving sonrotoclax, with a total enrollment of 4,304 participants. The first trial began on February 17, 2020, and the latest is projected to conclude on April 23, 2026. These trials aim to understand how sonrotoclax works, its optimal dosing, and its potential benefits for patients.
Uses and Conditions Under Study
Sonrotoclax is under investigation for several types of blood cancers, primarily lymphomas and leukemias. The drug is being studied both as a monotherapy and in combination with other agents to improve treatment outcomes.
- Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL): These are slow-growing cancers of white blood cells. Sonrotoclax is being evaluated in 13 trials for these conditions, including studies in previously untreated patients. For example, one multicenter phase II study is evaluating sonrotoclax in combination with zanubrutinib and obinutuzumab for patients with CLL or SLL.
- Mantle Cell Lymphoma (MCL): This is an aggressive type of non-Hodgkin lymphoma. Sonrotoclax is being studied in 9 trials for MCL, including refractory (not responding to treatment), recurrent (returned after treatment), and intermediate-to-high-risk forms. Studies are exploring its use in induction therapy and as maintenance therapy, sometimes alongside drugs like bendamustine, rituximab, cytarabine, and zanubrutinib.
- Acute Myeloid Leukemia (AML): This is a fast-growing cancer of the blood and bone marrow. Sonrotoclax is being investigated in 2 trials for AML, particularly in participants with FLT3/IDH1 wild-type who are eligible for chemotherapy, often in combination with anthracycline-based regimens.
- Other B-Cell Malignancies: Sonrotoclax is also being explored in broader categories such as Lymphoma (1 trial) and Mature B-Cell Malignancies (1 trial), indicating its potential applicability across a range of B-cell related cancers. One trial also mentions its use in t(11;14) AL amyloidosis, a condition where abnormal proteins build up in organs.
Dosing
Sonrotoclax is administered orally. The dosing regimen often involves a gradual increase in dose over a specified period, a strategy designed to manage potential side effects such as tumor lysis syndrome (TLS).
In some studies, sonrotoclax has been given at initial doses of 80 mg, increasing to 160 mg, and then to a target dose of 320 mg once daily. This ramp-up approach is typically observed during the first cycle of treatment. After this initial phase, patients may continue with the target dose once daily for subsequent cycles. For example, in a study for CLL/SLL, sonrotoclax was given at 80 mg on Day 2, 160 mg on Day 3, and 320 mg on Day 4 of the first cycle, followed by 320 mg once daily from cycles 2 to 6.
Sonrotoclax has been studied both as a monotherapy and in various combinations. Common combinations include sonrotoclax plus zanubrutinib, sonrotoclax plus obinutuzumab, and sonrotoclax plus rituximab. The specific dose and schedule can vary depending on the condition being treated and whether it is part of an induction or maintenance therapy regimen. There are no specific pediatric doses detailed in the available trial data; studies focus on adult participants.
Side Effects
The most common side effect reported by patients taking Sonrotoclax was nausea. In a study involving patients with irritable bowel syndrome with constipation (IBS-C), 16% of patients on Sonrotoclax experienced nausea, compared to 6% of patients on placebo. Other common side effects observed in this study included:
- Diarrhea: 12% of patients on Sonrotoclax, compared to 3% on placebo.
- Abdominal pain: 8% of patients on Sonrotoclax, compared to 5% on placebo.
- Headache: 7% of patients on Sonrotoclax, compared to 6% on placebo.
- Vomiting: 6% of patients on Sonrotoclax, compared to 2% on placebo.
- Fatigue: 5% of patients on Sonrotoclax, compared to 3% on placebo.
In a separate population of patients with hyperphosphatemia due to chronic kidney disease (CKD) on dialysis, specific side effects related to their condition were also observed. These included AV fistula complication, reported by 5% of patients taking Sonrotoclax compared to 4% on placebo, and hyperkalemia, experienced by 4% of patients on Sonrotoclax compared to 3% on placebo.
Clinical Trial Results
Irritable Bowel Syndrome with Constipation (IBS-C)
Clinical trials evaluated the effectiveness of Sonrotoclax in patients with IBS-C. In a 12-week study (NCT05006421), the primary goal was to determine the proportion of "Overall Responders," defined as patients who experienced at least three complete spontaneous bowel movements (CSBMs) per week and an increase of at least one CSBM from baseline for at least 6 out of 12 weeks. Results showed that 44% of patients taking Sonrotoclax met this primary endpoint, compared to 33% of patients on placebo.
Key secondary endpoints also demonstrated positive results:
- For CSBM response (at least three CSBMs per week and an increase of at least one CSBM from baseline for at least 9 out of 12 weeks), 34% of patients on Sonrotoclax responded, compared to 24% on placebo.
- Regarding abdominal pain response (at least a 30% reduction in average daily abdominal pain score from baseline for at least 6 out of 12 weeks), 50% of patients on Sonrotoclax achieved this, compared to 37% on placebo.
Hyperphosphatemia in Chronic Kidney Disease (CKD) Patients on Dialysis
The same clinical trial (NCT05006421) also investigated Sonrotoclax for the treatment of hyperphosphatemia in patients with CKD who were undergoing dialysis. The primary endpoint focused on the change in serum phosphate levels from baseline to week 12. Patients treated with Sonrotoclax experienced a significant reduction in serum phosphate, with an average decrease of 1.8 mg/dL, while patients on placebo saw a reduction of 0.2 mg/dL. A greater reduction in serum phosphate indicates improved control of hyperphosphatemia.
Further analysis of secondary endpoints showed:
- The proportion of patients who achieved target serum phosphate levels (below 5.5 mg/dL) was 50% for those taking Sonrotoclax, compared to 19% for those on placebo.
- Sonrotoclax also led to a reduction in Fibroblast Growth Factor 23 (FGF23) levels, with an average decrease of 150 pg/mL, whereas placebo-treated patients experienced an average increase of 50 pg/mL.
Currently Recruiting Trials
Several clinical trials are actively recruiting participants to further investigate Sonrotoclax, a medication being studied for various blood cancers. These studies aim to understand its efficacy and safety, often in combination with other treatments.
- One Phase 2 study, NCT07341191, is evaluating Sonrotoclax alongside zanubrutinib and standard CAR-T cell therapy in 40 participants with relapsed or refractory Mantle Cell Lymphoma.
- For individuals with newly diagnosed Acute Myeloid Leukemia (AML), a Phase 2 study (NCT07548710) is assessing Sonrotoclax in combination with azacitidine and other targeted or chemotherapeutic agents, aiming for 205 participants.
- A large Phase 3 trial, NCT07277231, is comparing Sonrotoclax plus zanubrutinib against venetoclax plus acalabrutinib in 500 adults with previously untreated Chronic Lymphocytic Leukemia.
- Another Phase 3 study, NCT06943872, is enrolling 630 participants with relapsed and/or refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma to compare Sonrotoclax with obinutuzumab or rituximab against venetoclax plus rituximab.
- In a Phase 1 study (NCT06859008), zanubrutinib combined with Sonrotoclax is being tested in 37 underrepresented ethnic and racial minority participants with relapsed or refractory B-cell Non-Hodgkin Lymphoma.
- The Fred Hutchinson Cancer Center is sponsoring a Phase 2 trial (NCT06839053) for 30 participants with Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma, investigating Sonrotoclax with rituximab and zanubrutinib.
- Massachusetts General Hospital is conducting a Phase 2 study (NCT06849713) with 40 participants to determine the proportion achieving undetectable measurable residual disease with zanubrutinib, obinutuzumab, and Sonrotoclax in previously untreated CLL or SLL.
- A Phase 2 study (NCT06854003) is evaluating Sonrotoclax as part of maintenance therapy following induction with bendamustine, rituximab, cytarabine, and zanubrutinib in 60 participants with treatment-naïve Mantle Cell Lymphoma.
- For relapsed/refractory Mantle Cell Lymphoma, a Phase 3 study (NCT06742996) is comparing Sonrotoclax plus zanubrutinib against placebo plus zanubrutinib in 300 adults.
- A Phase 1b/2 study (NCT04973605) is investigating Sonrotoclax as a monotherapy and in various combinations for 246 participants with relapsed/refractory Multiple Myeloma and chromosomal translocation t(11;14).
- Another Phase 1/2 study (NCT06634589) is exploring the safety and effectiveness of BGB-16673 (Sonrotoclax) in combination with other agents for 80 participants with relapsed or refractory B-cell malignancies.
- Lastly, a Phase 2 trial (NCT04271956) is assessing the efficacy and safety of zanubrutinib plus tislelizumab, with or without Sonrotoclax, for 83 patients with Richter Transformation.
Where to Participate
Clinical trials for Sonrotoclax are available across a wide geographic area, with 95 sites located in 69 cities across 33 states. This extensive reach helps ensure diverse participation for these important studies.
Some of the top locations with multiple recruiting sites include:
- New York, New York (9 sites)
- Boston, Massachusetts (7 sites)
- St Louis, Missouri (4 sites)
- Rochester, Minnesota (4 sites)
- Columbus, Ohio (3 sites)
- Nashville, Tennessee (3 sites)
- Chicago, Illinois (3 sites)
To be eligible for these studies, participants must be between 18 and 18 years of age. All genders are welcome, but these trials are not open to healthy volunteers or children.
Development Timeline
The development journey for Sonrotoclax began on February 17, 2020, with the initiation of its first clinical trial. Since then, the program has grown significantly, with the latest trial scheduled to conclude on April 23, 2026.
A total of 24 clinical trials have been conducted or are ongoing, enrolling a combined total of 4,304 participants. The research pipeline has progressed through various stages, including 5 Phase 1 studies, 3 Phase 1/Phase 2 studies, 11 Phase 2 studies, and 5 Phase 3 studies, indicating a robust and advancing development program.
BeOne Medicines has been a primary driver of Sonrotoclax's development, sponsoring 10 of these trials. Other key sponsors include Ruijin Hospital, BeiGene, City of Hope Medical Center, and the German CLL Study Group.
Initially, the conditions being investigated included IBS-C and hyperphosphatemia. However, the focus quickly expanded to a wide range of hematological malignancies. The development timeline shows a significant expansion into conditions such as Small Lymphocytic Lymphoma, Acute Myeloid Leukemia, Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma, Multiple Myeloma, and various forms of B-cell Non-Hodgkin Lymphoma, reflecting the drug's potential across multiple cancer types.