DOI: 10.1200/jco-26-00550 ISSN: 0732-183X

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

Toby A. Eyre, Yuqin Song, Olivier Hermine, Yuerong Shuang, Wojciech Jurczak, João Samuel Farias, Carolina Mahuad, Muhit Özcan, Ron D. Jachimowicz, Tianlei Chen, Elena Ivanova, Xiaotong Li, Gabriel Man, Priscille Bourquelot, Remus Vezan, Michael Wang
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PURPOSE

Mantle cell lymphoma (MCL) is a rare and typically aggressive B-cell non-Hodgkin lymphoma characterized by recurrent relapse after short remissions. Sonrotoclax (BGB-11417) is a next-generation B-cell lymphoma 2 inhibitor with greater selectivity and potency than venetoclax, a shorter half-life, and no drug accumulation. Sonrotoclax monotherapy was evaluated in Bruton tyrosine kinase inhibitor–pretreated patients with relapsed/refractory (R/R) MCL.

METHODS

BGB-11417-201 (ClinicalTrials.gov identifier: NCT05471843 ) is an ongoing global, open-label, phase I/II trial. Sonrotoclax was orally administered once daily with gradual, 4-week ramp-up to 160 mg or 320 mg to mitigate tumor lysis syndrome (TLS). The primary end point was overall response rate by the independent review committee (ORR-IRC) per Lugano classification; secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

RESULTS

Overall, 125 patients were enrolled and assigned to receive sonrotoclax 160 mg (n = 10) or 320 mg (n = 115) target doses once daily. Most patients had advanced disease (stage IV, 78.3%) and were heavily pretreated (median prior therapies, 3). In efficacy-evaluable patients (n = 103), the ORR-IRC was 52.4% (95% CI, 42.4 to 62.4), a statistically significant increase versus the historic control ORR (30%; P < .0001); the complete response rate was 15.5%. Responses were seen across high-risk subgroups, including patients with TP53 mutation (59.1%). With a median study follow-up of 14.2 months, the median DOR-IRC was 15.8 months, and the median PFS-IRC was 6.5 months. Median OS was not reached. The most common all-grade/grade ≥3 treatment-emergent adverse events were neutropenia (35.7%/19.1%), thrombocytopenia (24.3%/9.6%), and anemia (24.3%/7.8%). TLS occurred in 7.0% of patients; all cases resolved without sequelae.

CONCLUSION

Sonrotoclax demonstrated rapid, durable responses and manageable safety in heavily pretreated patients with R/R MCL, including high-risk subgroups, supporting its further clinical evaluation as an oral therapy for R/R MCL.

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