Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
Sonrotoclax plus obinutuzumab appears to be well-tolerated and produces deep responses in patients with treatment-naïve CLL / SLL.
Who Performed the Research and Where Was it Presented:
Dr. Marc Hoffmann from the University of Kansas Cancer Center and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting in 2025.
Background:
BCL2 inhibitors are a class of drugs that block BCL2, a protein that is overexpressed in chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) cells. The excess protein allows them to survive much longer than normal white blood cells. Venetoclax is a first-generation BCL2 inhibitor that received FDA approval for the treatment of CLL / SLL in 2016. Because it can kill CLL / SLL cells very rapidly, it must be ramped up gradually over a period of weeks to avoid tumor lysis syndrome. Now, second-generation BCL2 inhibitors are in development, including sonrotoclax, which is a more selective and potent inhibitor of BCL2. This study looked at the safety and preliminary efficacy of the combination of sonrotoclax plus obinutuzumab as a first-line treatment for patients with CLL / SLL.
Methods and Participants:
This study was part of a larger ongoing phase 1/1b, dose-escalation/expansion study (BGB-11417-101) in patients with B-cell cancers. For this arm of the study, patients with treatment-naïve CLL / SLL received sonrotoclax plus obinutuzumab for 15 cycles (a little over one year).
Results:
- A total of 55 patients with treatment-naïve CLL / SLL have enrolled in the study thus far.
- The median follow-up time at the time of analysis was 9 months.
- Efficacy could be evaluated in 37 patients, and the overall response rate was 89%.
- Thus far, 23 patients have reached the cycle 15 measurable residual disease (MRD) assessment.
- All patients with an available MRD assessment reached undetectable MRD (uMRD). Some patients reached cycle 15, but could not be evaluated for MRD or had missing data at the time of analysis.
- In the high-dose group (320 mg), the median time to reach uMRD was 2 months.
- The most common side effects were low platelets (56%), infusion-related reaction (56%), and low neutrophils (49%).
- No side effects led to treatment discontinuation or death.
- No clinical or laboratory tumor lysis syndrome occurred during sonrotoclax ramp up despite 14% or 8/55 patients having high tumor burden.
- One patient, who had discontinued treatment during cycle 1 of obinutuzumab, died from an indeterminate cause.
- Two patients developed progressive disease, which was Richter transformation in both cases.
Conclusions:
The results from this phase 1 clinical trial are encouragingly deep and quick. Sonrotoclax plus obinutuzumab appeared to be well-tolerated with no unexpected safety concerns and produced deep responses in patients with CLL / SLL. Longer studies will be needed to see if reaching uMRD with this combination also translates into longer progression-free survival, but that has proven to be the case with other combinations. Sonrotoclax is also being studied in combination with zanubrutinib, and we have previously reported on these results here: Sonrotoclax and Zanubrutinib as a Frontline CLL Treatment.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: MRD-guided therapy of sonrotoclax (BGB-11417) + obinutuzumab (O) in patients with treatment-naive CLL: Initial results from an ongoing phase 1/1b study, BGB-11417-101
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