Preliminary Safety and Antileukemic Activity of Sonrotoclax (BGB-11417), a Potent andSelective BCL2 Inhibitor, in Patients with Relapsed/Refractory Acute Myeloid LeukemiaAuthors: Pau Montesinos,1 Paul Cannell,2 Jake Shortt,3 Teng Fong Ng,4 David M. Swoboda,5Sophie Leitch,6 Chun Yew Fong,7 Uwe Platzbecker,8 Andrew H. Wei,9 Si Cheng,10 AdamGreenbaum,11 Yu Liu,12 Kendra Sweet,11 Amit Agarwal,11 Courtney DiNardo13Affiliations: 1Hospital Universitari I Politecnic La Fe, Valencia, Spain; 2Fiona Stanley Hospital,
Murdoch WA, Australia; 3Monash Health and Monash University, Clayton, VIC, Australia; 4Gold
Coast University Hospital, Gold Coast, Queensland, Australia; 5Tampa General Hospital,Tampa, FL, USA; 6North Shore Hospital, Auckland, New Zealand; 7Austin Health, Melbourne,Australia; 8Universitaetsklinikum Leipzig Aor, Leipzig, Germany; 9Peter MacCallum Cancer
Centre, Royal Melbourne Hospital, Melbourne, VIC, Australia; 10BeiGene (Shanghai) Co., Ltd.,
Shanghai, China; 11BeiGene USA, Inc, San Mateo, CA, USA; 12BeiGene (Beijing) Co., Ltd.,
Beijing, China; 13MD Anderson Cancer Center, Houston, TX, USA
Background: B-cell lymphoma 2 (BCL2), a key regulator of apoptosis, is overexpressed inmany hematologic malignancies. Although treatment with the BCL2 inhibitor venetoclax has
improved outcomes in some patients (pts) with newly diagnosed acute myeloid leukemia (AML),
it is not approved in relapsed/refractory (R/R) AML. Historically, available salvage regimens for
R/R AML have produced CR/CRh rates of 5%-35% and overall survival of 3-9 months,
depending on the regimen and the presence/absence of targetable mutations. Sonrotoclax(BGB-11417), a next-generation BCL2 inhibitor, is a more selective and pharmacologicallypotent inhibitor of BCL2 vs venetoclax. Here we present data with sonrotoclax + azacitidine inpts with R/R AML.
Aims: To present preliminary safety and antileukemic activity of sonrotoclax + azacitidine in pts
with R/R AML in BGB-11417-103 (NCT04771130; EudraCT: 2021-003285-12).
Methods: BGB-11417-103 is an ongoing, phase 1b/2, global, multicenter, dose finding andexpansion study evaluating sonrotoclax + azacitidine in pts with AML, myelodysplastic
syndrome (MDS), or MDS/myeloproliferative neoplasm. Pts who received prior BCL2 inhibitors
were excluded. Prior HMA was allowed. In cycle 1, a 4-day ramp-up of sonrotoclax began at
one-eighth of the target dose. Dose-limiting toxicities (DLTs) were assessed up to day 28 for

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nonhematologic toxicities and day 42 or cycle 2 initiation for hematologic toxicities. Treatmentemergent AEs (TEAEs) were graded per CTCAE v5.0. The primary endpoint was safety andtolerability of the combination. Response assessment was conducted according to theEuropean Leukemia Net (ELN) 2017 criteria.

Results: As of September 25, 2023, a total of 39 pts with R/R AML (13% with HMA failure) wereenrolled across dose escalation and expansion cohorts and were included in the safety
evaluation. Ten remain on treatment. Median age in all enrolled patients was 63 (range, 29-80)
years and 59% had ELN 2017 adverse risk AML. Median number of prior lines of therapy was 1(range, 1-4). Baseline characteristics are noted in Table 1. Seven dose cohorts have been
evaluated in R/R AML so far: sonrotoclax 40 mg x 10 days, 80 mg x 10 days, 160 mg x 10 days,
160 mg x 21 days, 160 mg x 28 days, 320 mg x 14 days, or 320 mg x 21 days + azacitidine (75mg/m2 x 7 days). At a median follow-up of 6.3 months, 1 pt had a DLT (grade 4thrombocytopenia; 320 mg x 14 days). All pts had ≥1 TEAE. The most common grade ≥3
nonhematologic TEAEs were vomiting, hypokalemia, and hypotension (all 8%); common grade≥3 hematologic TEAEs were neutropenia (49%), anemia (36%), febrile neutropenia (36%), andthrombocytopenia (33%). Grade ≥3 infections occurred in 46% of pts. Six pts (15%) had TEAEs
leading to sonrotoclax dose reductions. The most common TEAE class leading to sonrotoclax
discontinuation was infection (5%). No cases of tumor lysis syndrome occurred. Three ongoing
pts had not reached the first response assessment timepoint as of the data cutoff date; thus, 36
patients were included in the efficacy analysis. CR and CR/CRh rates were 28% and 47%,respectively. Median time to CR and CR/CRh was 2.8 and 1.5 months, respectively. Medianduration for both CR and CR/CRh was 13.1 months. Eight pts (21%) proceeded to allogeneic
stem cell transplant. Preliminary median overall survival was 11.8 (95% CI, 7.4-NE) months.

Summary/Conclusion: In this ongoing dose escalation phase 1b/2 trial, sonrotoclax +azacitidine was generally well tolerated. This combination demonstrated promising antileukemic
activity in pts with R/R AML including in the lowest dose cohorts. Further evaluation in pts withR/R AML is ongoing.

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