Medically reviewed by Dr. Brian Koffman
The Bottom Line:
Early data on a combination of sonrotoclax plus zanubrutinib for previously untreated CLL / SLL is very promising. Clinical trials testing this combination are open and enrolling patients.
Who Performed the Research and Where Was it Presented:
In this interview, Dr. Mazyar Shadman from Fred Hutchinson Cancer Center and Dr. Brian Koffman discuss current clinical trials using fixed-duration combination therapies taken orally. Dr. Constantine Tam from Alfred Health and Monash University and colleagues presented one of the studies discussed at the American Society for Hematology (ASH) Annual Meeting in 2023.
Background:
The treatment landscape for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) has changed dramatically in the last decade as we have moved from chemotherapy to targeted therapies. Now, researchers are looking to develop new combination therapies that can be taken for a limited period of time and consist of all oral therapies. In this interview, Dr. Shadman highlights two clinical trials doing this work with second-generation BTK inhibitors (acalabrutinib, zanubrutinib) and BCL2 inhibitors (sonrotoclax).
- Phase 3 clinical trial of acalabrutinib + venetoclax vs. venetoclax + obinutuzumab for previously untreated CLL / SLL
This study, also known as the MAJIC study, compares two excellent treatment options. It is currently ongoing but is no longer recruiting patients.
- Phase 1/2 clinical trial of sonrotoclax + zanubrutinib for previously untreated CLL / SLL
The initial results of this trial were presented at ASH 2023 and are discussed below. This trial is still ongoing and open to patients with various B-cell cancers, including CLL / SLL. Sonrotoclax is a second-generation BCL2 inhibitor that is more potent than venetoclax.
Methods and Participants:
This is an ongoing phase 1/2 clinical trial of sonrotoclax + zanubrutinib in patients with various B-cell cancers. The data presented here are from patients with previously untreated CLL / SLL. To minimize the risk of tumor lysis syndrome, patients received zanubrutinib for 8 to 12 weeks before starting the sonrotoclax ramp-up.
Results:
- At the time of data analysis (May 2023), 94 patients with treatment-naïve CLL / SLL were enrolled in the trial.
- The median follow-up was relatively short (8.5 months) since it is still early in the study.
- There were no cases of tumor lysis syndrome, a known side effect of venetoclax treatment.
- The most common side effects were bruising, low white blood cell count, and gastrointestinal issues.
- A total of 56 patients had a response assessment, and all patients responded to treatment (overall response rate = 100%).
- No patients have experienced disease progression thus far.
- Over half of patients had achieved undetectable measurable residual disease at six months.
Conclusions:
Thus far, the data on a combination of sonrotoclax plus zanubrutinib is very promising. All patients have responded, none have relapsed, and there have been no cases of tumor lysis syndrome. We look forward to seeing if these results hold as the trial progresses. This trial is still open to patients with various B-cell cancers. If you are interested in participating, more information can be found here: Study of Bcl-2 Inhibitor BGB-11417 in Participants With Mature B-Cell Malignancies.
As Dr. Shadman mentioned, a phase 3 clinical trial comparing sonrotoclax + zanubrutinib vs. venetoclax + obinutuzumab for CLL / SLL recently opened. If you are interested in participating, more information can be found here: Study of Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Obinutuzumab in Participants With Chronic Lymphocytic Leukemia (CLL)
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Combination Treatment with Sonrotoclax (BGB-11417), a Second-Generation BCL2 Inhibitor, and Zanubrutinib, a Bruton Tyrosine Kinase (BTK) Inhibitor, Is Well Tolerated and Achieves Deep Responses in Patients with Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (TN-CLL / SLL): Data from an Ongoing Phase 1/2 Study
Take care of yourself first.
Ann Liu, PhD
