BGB-11417-203, an ongoing, phase 2 study of sonrotoclax (BGB-11417), a nextgeneration BCL2 inhibitor, in patients with Waldenström macroglobulinemia

Authors: Jeffrey V. Matous,1 Hui-Peng Lee,2 Stephen Opat,3 John Hrom,4 David Kliman,5Paula Marlton,6 Peng Liu,7 Chenmu Du,8 Amber Lussier,9 Jun Zhang,9 Haiyi Guo,10 Steven
Treon11Affiliations: 1Colorado Blood Cancer Institute, Denver, CO, USA; 2Flinders Medical Centre,
Bedford Park, SA, Australia; 3Lymphoma Research Group, School of Clinical Sciences at
Monash Health, Monash University, Clayton, VIC, Australia; 4Hattiesburg Clinic, Hattiesburg,MS, USA; 5Genesis Care North Shore, St Leonards, NSW, Australia; 6Princess Alexandra
Hospital and University of Queensland, Brisbane, QLD, Australia; 7Affiliated Zhongshan
Hospital of Fudan University, Shanghai, China; 8BeiGene (Beijing) Co, Ltd, Beijing, China;
9

BeiGene USA, Inc, San Mateo, CA, USA; 10BeiGene (Shanghai) Co, Ltd, Shanghai, China;

11Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

Background: Bruton tyrosine kinase (BTK) inhibitors and anti-CD20 antibody–based
systemic therapies are included within the preferred treatment algorithms for Waldenström
macroglobulinemia (WM). However, to date, no treatments have been approved for patientswith WM that is refractory to both BTK inhibitors and anti-CD20–based therapy. Venetoclax,
the first-generation BCL2 inhibitor, has demonstrated clinical activity in patients withrelapsed/refractory (R/R) WM (Castillo et al. J Clin Oncol. 2022), but venetoclax has noregulatory approvals in WM. Sonrotoclax, a next-generation BCL2 inhibitor, is more selective
and a more pharmacologically potent inhibitor of BCL2 than venetoclax. In a phase 1 trial,
sonrotoclax monotherapy was well tolerated at all tested dose levels ≤640 mg and showedpromising evidence of antitumor activity in patients with R/R WM (Soumerai et al. Blood.
2022). Based on the data from these earlier studies, a phase 2 study of sonrotoclax
monotherapy in patients with R/R WM has been initiated and is currently recruiting.
Methods: BGB-11417-203 (NCT05952037) is an open-label, international, phase 2 study.
Eligible patients have histologically confirmed WM that is R/R to both BTK inhibitor therapy
and anti-CD20–based systemic therapy combined with chemotherapy or a proteasome
inhibitor (PI; cohort 1); R/R to anti-CD20–based systemic therapy combined withchemotherapy or a PI and intolerance of BTK inhibitor therapy (cohort 2); or R/R to a BTK
EHA 2024

inhibitor and unsuitable for chemoimmunotherapy (cohort 3). Patients who have received
previous treatment with a BCL2 inhibitor are ineligible. Approximately 85 patients will beenrolled across cohorts to receive sonrotoclax until disease progression, death, unacceptabletoxicity, patient withdrawal, loss to follow-up, or study termination. The primary endpoint ismajor response rate (MRR; defined as partial response or better) in cohort 1 per IWWM-11
criteria, as assessed by an independent review committee (IRC). Key secondary endpoints
include MRR assessed by investigator (INV) in cohort 1 and by IRC and INV in both cohorts 2
and 3; overall response rate, duration of response, and progression-free survival by IRC andINV; overall survival; and safety and tolerability. Patient recruitment is ongoing in Australia,
the US, China, and Europe.

EHA 2024