Dp003 | Combination Treatment With Novel Bcl2 Inhibitor Sonrotoclax (bgb-11417) and Zanubrutinib Induces High Rate of Complete Remission for Patients With Relapsed/refractory Mantle Cell Lymphoma
Year: 2025
Type: article
Abstract: BACKGROUND: Sonrotoclax (sonro; BGB-11417), a next-generation BCL2 inhibitor, is a more selective and pharmacologically potent inhibitor of BCL2 than venetoclax. Zanubrutinib (zanu), a next-generation BTK inhibitor (BTKi), is approved for R/R MCL. Updated safety and efficacy of sonro + zanu in R/R MCL in the ongoing BGB-11417-101 (NCT04277637) study are reported. METHODS: Patients (pts) with ≥1 prior treatment [tx] for MCL received zanu (320 mg QD/160mg BID) 8-12 wk before sonro ramp-up to the target dose (80, 160, 320, or 640mg QD) to prevent tumor lysis syndrome (TLS) risk; tx continued until progressive disease (PD)/unacceptable toxicity. Dose expansion occurred at 160 and 320 mg. The primary endpoint was safety (CTCAE v5.0); a secondary endpoint was ORR per 2014 Lugano classification. RESULTS: As of 6 Dec 2024, 49 pts with R/R MCL were enrolled and treated (sonro 80 mg, n=6; 160 mg, n=13; 320 mg, n=25; 640 mg, n=5): 7 were in zanu lead-in; 42 started sonro. Pts had a median of 1 prior tx (range, 1-4; stem cell transplant, n=15 [1 allogeneic, 14 autologous]; CAR T-cell therapy, n=1; BTKi, n=3). Median follow-up was 16.2 mo (range, 0.6-39.7). MTD was not reached up to sonro 640mg; the RP2D was 320 mg. Overall, 20 pts (40.8%) discontinued (d/c) ≥1 tx: 7 d/c zanu only (5 PD during zanu lead-in; 2 AE [diarrhea, meningitis]); 13 d/c sonro + zanu (8 PD, 4 AE [myelodysplastic syndrome, pneumonia, diarrhea, abdominal sepsis], 1 pt withdrawal). Eight pts died due to PD (4 during zanu lead-in). Tx-emergent AEs (TEAEs) in ≥30% of pts were contusion, COVID-19, diarrhea, and neutropenia (30.6% each). The most common grade ≥3 TEAE was neutropenia (20.4%). No laboratory or clinical TLS occurred. No atrial fibrillation/flutter or ventricular arrhythmia occurred. TEAEs led to 2 deaths (4.1%; 1 pneumonia, 1 abdominal sepsis [not tx-related]). In 45 evaluable pts across doses, ORR was 77.8% (CR, n=28; 62.2%) (Figure). Median time to CR was 6.7 mo; at data cutoff, 89% (25/28) remained in CR. In the 160 and 320mg expansion cohorts (median follow-up, 16.2 and 12.9 mo, respectively), ORR was 76.9% (CR, n=7; 53.8%) and 76.2% (CR, n=13; 61.9%), respectively. Two of 3 evaluable pts with prior BTKi tx had partial responses and 1 had PD. CONCLUSIONS: Sonro + zanu was well tolerated and had encouraging antitumor activity, with a CR rate of 62.2%, and responses in pts with prior BTKi tx. A registrational phase 3 study (NCT06742996) with sonro 320mg + zanu is recruiting.
Authors: C. Visco, C.S. Tam, M. Lasica, J.D. Soumerai, S.S. Opat, M.S. Hoffmann, R. García-Sanz, J. Schetelig, T. Munir, R. Weinkove, P. Browett, E. González-Barca, L. Magnano Mayer, A. Bernardelli, J-Z. Hou, Y. Fang, J. Hilger, S. Patel, R. Cordoba
Institutions: University of Verona, The Alfred Hospital, Monash University, St Vincent's Hospital Melbourne, Harvard University, Massachusetts General Hospital, Monash Health, University of Kansas, The University of Kansas Cancer Center, Hospital General Universitario Gregorio Marañón, Centro de Investigación Biomédica en Red de Cáncer, University Hospital Carl Gustav Carus, Technische Universität Dresden, Leeds Teaching Hospitals NHS Trust, Malaghan Institute of Medical Research, Health New Zealand, Auckland City Hospital, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Universitat de Barcelona, Hospital Clínic de Barcelona, Azienda Ospedaliera Universitaria Integrata Verona, University of Pittsburgh Medical Center, Hospital Universitario Fundación Jiménez Díaz
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093123751
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