Sonrotoclax monotherapy produced durable responses in Chinese patients with relapsed/refractory mantle cell lymphoma.
Sonrotoclax (Beqalzi) monotherapy had clinically meaningful activity in Chinese patients with heavily pretreated, relapsed/refractory mantle cell lymphoma (MCL), according to a China subpopulation analysis of the phase 1/2 BGB-11417-201 trial (NCT05471843) presented at the
Notably, data from the overall population of the trial supported the
In the China subpopulation analysis, an overall response rate (ORR) per independent review committee (IRC) of 61.8% (95% CI, 43.6%-77.8%) was reported with the monotherapy in Chinese patients with BTK inhibitor–pretreated relapsed/refractory MCL (n = 34).1 The IRC-assessed complete response rate for these patients was 26.5% (95% CI, 12.9%-44.4%), and at a median study follow-up of 15.6 months (95% CI, 10.2-20.6), the median duration of response (DOR) by IRC was 15.8 months (95% CI, 7.4–not evaluable [NE]). Moreover, at a median follow-up of 17.4 months (95% CI, 12.0-22.8), the median progression-free survival (PFS) per IRC was 11.9 months (95% CI, 6.3-19.8), and the median overall survival (OS) was not reached (95% CI, 7.7 months-NE) at a median follow-up of 18.7 months (95% CI, 16.2-21.0).
“Sonrotoclax monotherapy demonstrated clinically meaningful activity in heavily pretreated patients with MCL in China,” lead study author Yuqin Song, MD, PhD, and coauthors wrote in a presentation of the data. “[These data are] similar to the overall population [data from the trial].”
Song is the vice director and chief doctor of the Lymphoma Department at Peking University Cancer Hospital in Beijing, China.
The ongoing, open-label, multicenter trial enrolled patients who were at least 18 years with histologically confirmed MCL per World Health Organization 2016 classification. Patients also needed to have received at least prior 1 anti-CD20–based therapy and at least 1 prior BTK inhibitor, have an ECOG performance status of 2 or less, and have not previously received a BCL-2 inhibitor.
In parts 1a and 1b of the study, sonrotoclax was administered orally once daily at target doses of 160 mg (n = 10) and then 320 mg (n = 12), achieved gradually over an approximately 4-week ramp-up period. In the efficacy-expansion part of the study, patients received sonrotoclax at the recommended phase 2 dose until they experienced disease progression (n = 103).
The primary end point of part 2 was ORR by IRC per Lugano 2014 criteria; secondary end points included ORR by investigator, DOR, PFS, OS, time to response (TTR), health-related quality of life, and safety.
As of the July 18, 2025, data cutoff, 55 patients in China had enrolled. The efficacy analysis included the 34 patients treated with sonrotoclax at 320 mg in part 2, and the safety analysis included all 45 patients assigned to receive that dose across parts 1 and 2.
Baseline characteristics revealed that Chinese patients in the analysis had a median age of 66 years (range, 50-81), and 73.3% of patients were male. Most patients had stage III or IV disease (88.9%), whereas fewer had bulky disease with a longest diameter of at least 5 cm (26.7%). Most patients had high or intermediate simplified MCL International Prognostic Index scores (64.5%) and had discontinued their last line of therapy due to disease progression (80.0%). TP53 mutations were observed in 31.4% of evaluable patients (n =35), bone marrow involvement was observed in 46.7% of patients, and 46.5% of evaluable patients (n = 43) had a Ki-67 score that was 30% or higher. Patients had also received a median of 2 prior lines of therapy (range, 1-8), and 20.0% of patients had received at least 2 distinct BTK inhibitors.
Across all safety-evaluable patients (n = 45), any-grade treatment-emergent adverse effects (TEAEs) occurred in 97.8%, and grade 3 or higher TEAEs occurred in 46.7%. Serious TEAEs occurred in 26.7% of patients. TEAEs led to treatment discontinuation in 8.9% of patients, and 4.4% of patients experienced grade 5 TEAEs.
Neutropenia was the most common any-grade TEAE (53.3%) and the most common grade 3 or higher TEAE (20.0%). Other common any-grade TEAEs were decreased white blood cell count (51.1%), hypokalemia (35.6%), and hyperuricemia (31.1%).
Any-grade tumor lysis syndrome occurred in 6.7% of patients, febrile neutropenia was reported in 2.2% of patients, and infections were seen in 35.6% of patients. Investigators reported that the incidences of grade 3 or higher TEAEs, serious TEAEs, and TEAEs leading to discontinuation were generally similar between the China subpopulation and the global population.
The investigators noted that the phase 3 CELESTIAL-RRMCL trial (NCT06742996) evaluating sonrotoclax in combination with zanubrutinib (Brukinsa) in patients with relapsed/refractory MCL is currently recruiting.
