UPDATED INTERIM RESULTS OF SONROTOCLAX + DEXAMETHASONE IN PATIENTS WITH T(11;14)-POSITIVE RELAPSED/REFRACTORY MULTIPLE MYELOMA (R/R MM): AN ALL-ORAL TREATMENT

IF 3.3 4区 医学 Q2 HEMATOLOGY
B. Dhakal, M. Hultcrantz, N. Nathwani, C. P. Venner, J. Lu, M. J. Slade, J. L. Kaufman, H. Chuah, C. Min, K. Kim, H. Cheng, A. Idoine, W. Zhang, X. Wang, A. Agarwal, H. Quach
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Updated results in pts treated with sonro + dexamethasone (dex) are presented.</p><p><b>Methods:</b> Eligible pts had R/R MM with centrally confirmed t(11;14) and received oral sonro (320 or 640 mg QD) + dex (40 mg QW). Tx-emergent adverse events (TEAEs) were graded by CTCAE v5.0 and efficacy was assessed by the investigator per IMWG criteria.</p><p><b>Results:</b> As of January 20, 2025, 14 and 36 evaluable pts were enrolled in the sonro 320-mg and 640-mg cohorts, respectively; median (range) follow-up was 6.2 mo (2.6–34.5) and 12.1 mo (0.1–28.9), respectively. The median (range) prior lines of tx were 3 (1–7) in the 320-mg cohort and 3 (1–12) in the 640-mg cohort; 78.6% and 66.7% of pts were refractory to 3 tx classes, respectively. At data cutoff, 7 pts (50.0%) in the 320-mg cohort and 14 (38.9%) in the 640-mg cohort remained on tx; progression was the most common reason for discontinuation (35.7% and 41.7%, respectively). The ORR (95% CI) was 64.3% (35.1–87.2) in the 320-mg cohort and 80.6% (64.0–91.8) in the 640-mg cohort, with VGPR or better rates (95% CI) of 35.7% (12.8–64.9) and 55.6% (38.1–72.1), respectively (Figure). The median time to response was 0.7 mo in both cohorts. Median (95% CI) duration of response was 5.9 mo (1.8-not estimable [NE]) in the 320-mg cohort and 12.2 mo (8.3–18.9) in the 640-mg cohort. Median (95% CI) PFS was 6.6 mo (2.9-NE) in the 320-mg cohort and 13.3 mo (9.0–19.6) in the 640-mg cohort.</p><p>The most common TEAEs were fatigue (35.7%) in the 320-mg cohort, and insomnia (38.9%) and diarrhea (38.9%, all grade 1/2) in the 640-mg cohort. Grade ≥ 3 TEAEs occurred in 5 pts (35.7%) in the 320-mg cohort and 17 pts (47.2%) in the 640-mg cohort; serious TEAEs occurred in 3 (21.4%) and 10 (27.8%), respectively. Grade ≥ 3 hematologic TEAEs occurred in 1 (7.1%) and 9 (25.0%) and grade ≥ 3 infections in 3 (21.4%) and 4 (11.1%) pts, respectively. Two pts (14.3%) in the 320-mg cohort and 2 (5.6%) in the 640-mg cohort died during the tx-emergent part for reasons unrelated to tx (320 mg, pneumonia RSV and COVID-19; 640 mg, hypoventilation [related to pulmonary involvement with PD] and metastatic pancreatic cancer). Four more deaths occurred &gt; 30 d after the last 640-mg dose.</p><p><b>Conclusions:</b> This ongoing study showed that the all-oral combination of sonro + dex is tolerable, with low rates of infection and hematologic toxicity, and promising efficacy, with an ORR of 81% in the 640-mg cohort, in this t(11;14)-positive R/R MM population. Additional tx combinations with sonro are being investigated.</p><p><b>Research</b> <b>funding declaration:</b> This study was sponsored by BeiGene, Ltd.</p><p><b>Encore Abstract:</b> EHA 2025</p><p><b>Keywords:</b> combination therapies; ongoing trials; multiple myeloma</p><p><b>Potential sources of conflict of interest:</b></p><p><b>B. 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引用次数: 0

Abstract

Introduction: Despite the clinical efficacy of BCL2 inhibition in t(11;14)-positive MM, no BCL2-targeted treatments (tx) are approved. Sonrotoclax (sonro; BGB-11417), a next-generation BCL2 inhibitor, is a more selective and pharmacologically potent inhibitor of BCL2 than venetoclax, with a shorter half-life and no drug accumulation. BGB-11417-105 (NCT04973605) is an ongoing phase 1b/2 study of sonro as mono- or combination tx in patients (pts) with t(11;14)-positive R/R MM. Updated results in pts treated with sonro + dexamethasone (dex) are presented.

Methods: Eligible pts had R/R MM with centrally confirmed t(11;14) and received oral sonro (320 or 640 mg QD) + dex (40 mg QW). Tx-emergent adverse events (TEAEs) were graded by CTCAE v5.0 and efficacy was assessed by the investigator per IMWG criteria.

Results: As of January 20, 2025, 14 and 36 evaluable pts were enrolled in the sonro 320-mg and 640-mg cohorts, respectively; median (range) follow-up was 6.2 mo (2.6–34.5) and 12.1 mo (0.1–28.9), respectively. The median (range) prior lines of tx were 3 (1–7) in the 320-mg cohort and 3 (1–12) in the 640-mg cohort; 78.6% and 66.7% of pts were refractory to 3 tx classes, respectively. At data cutoff, 7 pts (50.0%) in the 320-mg cohort and 14 (38.9%) in the 640-mg cohort remained on tx; progression was the most common reason for discontinuation (35.7% and 41.7%, respectively). The ORR (95% CI) was 64.3% (35.1–87.2) in the 320-mg cohort and 80.6% (64.0–91.8) in the 640-mg cohort, with VGPR or better rates (95% CI) of 35.7% (12.8–64.9) and 55.6% (38.1–72.1), respectively (Figure). The median time to response was 0.7 mo in both cohorts. Median (95% CI) duration of response was 5.9 mo (1.8-not estimable [NE]) in the 320-mg cohort and 12.2 mo (8.3–18.9) in the 640-mg cohort. Median (95% CI) PFS was 6.6 mo (2.9-NE) in the 320-mg cohort and 13.3 mo (9.0–19.6) in the 640-mg cohort.

The most common TEAEs were fatigue (35.7%) in the 320-mg cohort, and insomnia (38.9%) and diarrhea (38.9%, all grade 1/2) in the 640-mg cohort. Grade ≥ 3 TEAEs occurred in 5 pts (35.7%) in the 320-mg cohort and 17 pts (47.2%) in the 640-mg cohort; serious TEAEs occurred in 3 (21.4%) and 10 (27.8%), respectively. Grade ≥ 3 hematologic TEAEs occurred in 1 (7.1%) and 9 (25.0%) and grade ≥ 3 infections in 3 (21.4%) and 4 (11.1%) pts, respectively. Two pts (14.3%) in the 320-mg cohort and 2 (5.6%) in the 640-mg cohort died during the tx-emergent part for reasons unrelated to tx (320 mg, pneumonia RSV and COVID-19; 640 mg, hypoventilation [related to pulmonary involvement with PD] and metastatic pancreatic cancer). Four more deaths occurred > 30 d after the last 640-mg dose.

Conclusions: This ongoing study showed that the all-oral combination of sonro + dex is tolerable, with low rates of infection and hematologic toxicity, and promising efficacy, with an ORR of 81% in the 640-mg cohort, in this t(11;14)-positive R/R MM population. Additional tx combinations with sonro are being investigated.

Research funding declaration: This study was sponsored by BeiGene, Ltd.

Encore Abstract: EHA 2025

Keywords: combination therapies; ongoing trials; multiple myeloma

Potential sources of conflict of interest:

B. Dhakal

Consultant or advisory role: BMS, Janssen, Arcellx, Kite, Pfizer, Karyopharm, Genentech, Natera, Sanofi

Honoraria: BMS, Karyopharm

Other remuneration: Speaker's bureau: Janssen, Sanofi, Karypharm, BMS

M. Hultcrantz

Consultant or advisory role: BMS, Johnson & Johnson

Other remuneration: Research funding: GSK, AbbVie, BeiGene, Daiichi Sankyo

C. P. Venner

Honoraria: Forus, AbbVie, Pfizer, Johnson & Johnson, Amgen, Sanofi

M. J. Slade

Honoraria: Menarini Silicon Biosystems

Other remuneration: Research funding: Pfizer

J. L. Kaufman

Consultant or advisory role: AbbVie, Ascentage, BMS, Genentech, Sanofi, Sebia, Incyte

Other remuneration: Research funding: AbbVie, BeiGene, BMS, Genentech, Heidelberg Pharma AG, Janssen, Novartis, Pfizer, Takeda

H. Chuah

Consultant or advisory role: AbbVie

Other remuneration: Speaker's bureau: BeiGene; Travel, accommodations, expenses: Janssen

H. Cheng

Employment or leadership position: BeiGene

Stock ownership: BeiGene

A. Idoine

Employment or leadership position: BeiGene

Stock ownership: BeiGene

Other remuneration: Travel, accommodations, expenses: BeiGene

W. Zhang

Employment or leadership position: BeiGene

Stock ownership: BeiGene

X. Wang

Employment or leadership position: BeiGene

Stock ownership: BeiGene

A. Agarwal

Employment or leadership position: BeiGene

Stock ownership: BeiGene

H. Quach

Consultant or advisory role: GSK, AbbVie, BMS, Pfizer, Johnson & Johnson, Roche

Other remuneration: Research funding: GSK, AbbVie, BMS

Abstract Image

sonrotoclax +地塞米松治疗t(11;14)阳性复发/难治性多发性骨髓瘤(r / r mm)患者的最新中期结果:全口服治疗
尽管BCL2抑制t(11;14)阳性MM具有临床疗效,但尚未批准BCL2靶向治疗(tx)。Sonrotoclax (sonro;BGB-11417)是新一代BCL2抑制剂,是一种比venetoclax更具选择性和药理效力的BCL2抑制剂,半衰期更短,无药物蓄积。BGB-11417-105 (NCT04973605)是一项正在进行的1b/2期研究,将sonro作为单药或联合治疗t(11;14)阳性R/R MM患者(pts)。方法:符合条件的患者有R/R MM,中央确认t(11;14),口服sonro(320或640 mg QD) + dex (40 mg QW)。采用CTCAE v5.0对tx紧急不良事件(teae)进行分级,研究者根据IMWG标准对疗效进行评估。结果:截至2025年1月20日,分别有14名和36名可评估患者入组sonro 320-mg和640-mg队列;中位(范围)随访时间分别为6.2个月(2.6-34.5)和12.1个月(0.1-28.9)。在320毫克组中,tx的中位(范围)为3(1-7)条,在640毫克组中为3(1-12)条;78.6%和66.7%的PTS分别为3 tx级难治。在数据截止时,320毫克组中有7例(50.0%)和640毫克组中有14例(38.9%)仍在服用tx;进展是最常见的停药原因(分别为35.7%和41.7%)。320毫克组的ORR (95% CI)为64.3%(35.1-87.2),640毫克组的ORR为80.6% (64.0-91.8),VGPR或更优率(95% CI)分别为35.7%(12.8-64.9)和55.6%(38.1-72.1)(图)。两组患者的中位反应时间均为0.7个月。中位(95% CI)反应持续时间在320毫克组为5.9个月(1.8-不可估计[NE]),在640毫克组为12.2个月(8.3-18.9)。320毫克组的中位(95% CI) PFS为6.6个月(2.9-NE), 640毫克组的中位PFS为13.3个月(9.0-19.6)。320毫克组最常见的teae是疲劳(35.7%),640毫克组最常见的teae是失眠(38.9%)和腹泻(38.9%,均为1/2级)。≥3级teae在320 mg组中发生5例(35.7%),在640 mg组中发生17例(47.2%);严重teae分别为3例(21.4%)和10例(27.8%)。1例(7.1%)和9例(25.0%)发生≥3级血液学teae, 3例(21.4%)和4例(11.1%)分别发生≥3级感染。320 mg组中2例(14.3%)和640 mg组中2例(5.6%)因与tx (320 mg、肺炎RSV和COVID-19无关的原因死亡;640毫克,低通气[与PD肺部受累有关]和转移性胰腺癌)。又有四人死亡。最后一次640毫克剂量后30天。结论:这项正在进行的研究表明,在t(11;14)阳性R/R MM人群中,全口服联合sonro + dex是可耐受的,具有低感染率和血液毒性,并且有希望的疗效,在640 mg队列中ORR为81%。正在研究与sonro的其他tx组合。研究经费声明:本研究由百济神州股份有限公司(BeiGene, ltd .)赞助。正在进行试验;潜在的利益冲突来源:B。顾问或顾问角色:BMS、Janssen、Arcellx、Kite、Pfizer、Karyopharm、Genentech、Natera、SanofiHonoraria: BMS、KaryopharmOther薪酬:发言人局:Janssen、Sanofi、Karypharm、BMSM。顾问或顾问角色:BMS, Johnson &;其他报酬:研究经费:GSK, AbbVie, BeiGene, Daiichi SankyoC。P. VennerHonoraria: Forus, AbbVie, Pfizer, Johnson &;强生,安进,赛诺菲。J. SladeHonoraria:美纳里尼硅生物系统公司其他报酬:研究经费:辉瑞公司。L. kaufman顾问或顾问角色:AbbVie, ascencentage, BMS, Genentech, Sanofi, Sebia, incyte其他报酬:研究经费:AbbVie, BeiGene, BMS, Genentech,海德堡制药公司,杨森,诺华,辉瑞,武德。顾问或顾问角色:abbview其他报酬:演讲者办公室:百济神州;旅行、住宿、费用:工作或领导职务:贝吉纳股份:贝吉纳理想工作或领导职位:贝吉斯股份:贝吉斯其他报酬:差旅、住宿、费用:贝吉斯。工作或领导职务:贝健股份:贝健药业。工作或领导职务:贝吉纳股份:贝吉纳工作或领导职务:贝吉斯股份:贝吉斯顾问或顾问角色:GSK、AbbVie、BMS、Pfizer、Johnson &;其他报酬:研究经费:葛兰素史克,艾伯维,BMS
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来源期刊
Hematological Oncology
Hematological Oncology 医学-血液学
CiteScore
4.20
自引率
6.10%
发文量
147
审稿时长
>12 weeks
期刊介绍: Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged: -Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders -Diagnostic investigations, including imaging and laboratory assays -Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases -Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies -Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems. Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.
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