Sonrotoclax Monotherapy Demonstrates Meaningful Activity in Heavily Pretreated Mantle Cell Lymphoma

Clinical Summary:

• Design/Population: The global, phase 1/2 BGB-11417-201 trial evaluated sonrotoclax monotherapy in patients with relapsed or refractory mantle cell lymphoma previously treated with anti-CD20–based therapy and a covalent or noncovalent BTK inhibitor.
• Key Outcomes: At the recommended phase 2 dose of 320 mg once daily, sonrotoclax achieved a 52.4% overall response rate versus 30% historically (P < .0001), with a 15.5% complete response rate. Median duration of response was 15.8 months and median progression-free survival was 6.5 months, with responses also seen in high-risk subgroups.
• Clinical Relevance: Sonrotoclax demonstrated clinically meaningful single-agent activity in a heavily pretreated population with limited treatment options following BTK inhibitor therapy, supporting continued evaluation of this next-generation BCL2 inhibitor. 

According to results from the phase 1/2 BGB-11417-201 study, sonrotoclax monotherapy produced rapid and durable responses in patients with relapsed or refractory mantle cell lymphoma (MCL) previously treated with anti-CD20–based therapy and a Bruton tyrosine kinase (BTK) inhibitor, including patients with high-risk disease features. 

“While [standard first-line] regimens improve outcomes, most patients eventually develop resistance and progress,” stated Toby Eyre, MD, Churchill Hospital, Headington, Oxford, United Kingdom, and coauthors. “Consequently, a substantial unmet need remains for effective and well-tolerated treatments for relapsed or refractory MCL.” 

In this open-label trial, 125 patients received once daily sonrotoclax with a gradual 4-week ramp-up to a target dose of 160 mg (n = 10) or 320 mg (n= 115) to mitigate tumor lysis syndrome (TLS). The phase 2 efficacy expansion included 103 patients treated with 320 mg of once daily sonrotoclax. The primary end point was objective response rate (ORR), assessed via independent review. Key secondary end points included duration of response, progression-free survival (PFS), overall survival (OS), time to response, and safety.  

At a median follow-up of 14.2 months in the efficacy-evaluable population, ORR was 52.4%, significantly excdeeding the historical control rate of 30% (P < .0001). The complete response rate was 15.5%, and the median time to response was 1.9 months. Median duration of response was 15.8 months, with a 62.9% probability of an ongoing response at 9 months. Median PFS was 6.5 months, and the 12-month PFS rate was 35.1%. Median OS was not reached, with a 12-month OS rate of 67.4%.

Responses were also observed across several high-risk subgroups. ORRs were 59.1% among patients with TP53 mutations, 54.8% among those with bulky disease, 49.4% among patients refractory to their most recent therapy, and 47.2% among those with a Ki-67 of ≥30%. Among 14 patients previously treated with pirtobrutinib, the ORR was 50%.

Among patients treated with 320 mg of sonrotoclax, grade ≥3 treatment-emergent adverse event occurred in 52.2% of patients. The most common treatment-emergent adverse events included neutropenia, thrombocytopenia, and anemia. Serious treatment-emergent adverse events occurred in 37.4% of patients. Eight patients experienced TLS; all events were transient, resolved without sequelae, and did not result in treatment discontinuation.

 “These results suggest that sonrotoclax could represent an important development in the management of [relapsed or refractory] MCL,” concluded Dr Eyre et al. 

“This impressive single-agent activity informs the regulatory approval of sonrotoclax in relapsed or refractory MCL and suggests potential utility as bridging therapy prior to chimeric antigen receptor T-cell therapy in patients with MCL refractory to BTK inhibition,” added Journal of Clinical Oncology Editor-in-Chief, Jonathan Friedberg, MD, Wilmot Cancer Institute, Rochester, New York. “Ongoing trials are also investigating rational combinations including sonrotoclax.” 

Source:

Eyre TA, Song Y, Hermine O, et al. Phase I/II study of sonrotoclax (BGB-11417) monotherapy in patients with mantle cell lymphoma previously treated with anti-CD20 therapy and a bruton tyrosine kinase inhibitor. J Clin Oncol. Published online: July 1, 2026. doi: 10.1200/jco-26-00550