DREAMM-8 phase III trial showed statistically significant and clinically meaningful improvement in primary endpoint of progression-free survival (PFS)

DREAMM-8 III期试验显示，无进展生存期（PFS）的主要终点有统计学意义和临床意义的改善

Median PFS not yet reached at 21.8 months median follow-up versus 12.7 months in bortezomib combination

中位PFS在21.8个月的中位随访时间尚未达到，而硼替佐米联合治疗的中位随访时间为12.7个月

Second trial to show robust efficacy for a Blenrep combination versus a standard of care in second line and later relapsed/refractory multiple myeloma

第二项试验显示，Blenrep组合与二线和后来复发/难治性多发性骨髓瘤的标准治疗相比具有强大的疗效

Results simultaneously published in the New England Journal of Medicine

结果同时发表在《新英格兰医学杂志》上

GSK plc (LSE/NYSE: GSK) today announced positive results from an interim analysis of the DREAMM-8 phase III head-to-head trial evaluating Blenrep (belantamab mafodotin), in combination with pomalidomide plus dexamethasone (PomDex), versus a standard of care, bortezomib plus PomDex, as a second line and later treatment for relapsed or refractory multiple myeloma.

葛兰素史克股份有限公司（伦敦证交所/纽约证交所：葛兰素史克）今天宣布，对DREAMM-8 III期头对头试验的中期分析显示阳性结果，该试验评估了blerep（belantamab mafodotin）联合pomalidomide加地塞米松（PomDex）与标准治疗，硼替佐米加PomDex，作为复发或难治性多发性骨髓瘤的二线和后续治疗。

These late-breaking data, being presented today at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (31 May – 4 June) in Chicago, IL, were featured in the official ASCO press programme and simultaneously published in the New England Journal of Medicine..

这些最新的数据今天在伊利诺伊州芝加哥举行的2024年美国临床肿瘤学会（ASCO）年会（5月31日至6月4日）上发表，并在ASCO官方新闻节目中发表，同时发表在《新英格兰医学杂志》上。。

On the primary endpoint of progression-free survival (PFS), a statistically significant and clinically meaningful improvement (hazard ratio [HR]: 0.52 [95% confidence interval (CI): 0.37-0.73], p-value<0.001) was observed with the belantamab mafodotin combination (n=155) compared to the bortezomib combination (n=147).

在无进展生存期（PFS）的主要终点上，与硼替佐米联合用药（n=147）相比，belantamab-mafodotin联合用药（n=155）观察到统计学上显着且具有临床意义的改善（危险比[HR]：0.52[95%置信区间（CI）：0.37-0.73]，p值<0.001）。

At a median follow-up of 21.8 months, the median PFS was not yet reached (95% CI: 20.6-not yet reached [NR]) with the belantamab mafodotin combination compared to 12.7 months (95% CI: 9.1-18.5) in the bortezomib combination. At the end of one year, 71% (95% CI: 63-78) of patients in the belantamab mafodotin combination group compared to 51% (95% CI: 42-60) in the bortezomib combination group were alive and had not progressed.

在中位随访21.8个月时，belantamab-mafodotin联合治疗的中位PFS尚未达到（95%CI:20.6-尚未达到[NR]），而硼替佐米联合治疗的中位PFS为12.7个月（95%CI:9.1-18.5）。在一年结束时，belantamab-mafodotin联合组中71%（95%CI:63-78）的患者存活，而硼替佐米联合组中51%（95%CI:42-60）的患者存活并且没有进展。

A benefit for belantamab mafodotin plus PomDex was observed across all pre-specified subgroups including those with poor prognostic features, such as patients who were refractory to lenalidomide and patients with high-risk cytogenetics..

在所有预先指定的亚组中观察到belantamab-mafodotin加PomDex的益处，包括那些预后不良的亚组，例如来那度胺难治性患者和高危细胞遗传学患者。。

Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: “With the robust results from the DREAMM-8 phase III head-to-head trial, we now have consistent data from two phase III trials supporting the potential for Blenrep combinations to redefine the treatment of multiple myeloma at or after first relapse.

葛兰素史克公司研发全球肿瘤学负责人高级副总裁Hesham Abdullah说：“凭借DREAMM-8 III期头对头试验的有力结果，我们现在从两项III期试验中获得了一致的数据，支持Blenrep组合在首次复发时或复发后重新定义多发性骨髓瘤治疗的潜力。

This is exciting news given the high unmet need for new and efficacious combinations once patients relapse or stop responding to initial treatments. We continue to share data and discuss our path forward with regulators.”.

这是一个令人兴奋的消息，因为一旦患者复发或停止对初始治疗的反应，对新的有效组合的需求尚未得到满足。我们继续与监管机构分享数据并讨论我们的前进道路。”。

A positive overall survival (OS) trend was observed but not statistically significant (HR: 0.77 [95% CI: 0.53-1.14]) at the interim analysis. OS follow-up continues and further analyses are planned. At the end of one year, 83% (95% CI: 76-88) of patients were alive in the belantamab mafodotin combination group versus 76% (95% CI: 68-82) in the bortezomib combination group.

中期分析显示总生存率（OS）呈阳性趋势，但无统计学意义（HR:0.77[95%CI:0.53-1.14]）。操作系统的后续行动仍在继续，并计划进行进一步的分析。在一年结束时，belantamab-mafodotin联合组有83%（95%CI:76-88）的患者存活，而硼替佐米联合组有76%（95%CI:68-82）。

The safety and tolerability profile of the belantamab mafodotin combination was broadly consistent with the known profile of the individual agents..

belantamab-mafodotin组合的安全性和耐受性概况与个体药物的已知概况大致一致。。

Suzanne Trudel, MD, Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada, said: “The profound progression-free survival benefit seen in DREAMM-8 highlights the potential for belantamab mafodotin, when used with pomalidomide and dexamethasone, to improve outcomes for patients with relapsed/refractory multiple myeloma.

加拿大多伦多大学健康网络玛格丽特公主癌症中心医学肿瘤学和血液学系医学博士苏珊娜·特鲁德尔（SuzanneTrudel）说：“在DREAMM-8中看到的深刻的无进展生存益处突出了belantamab-mafodotin与pomalidomide和地塞米松联用时的潜力，以改善复发/难治性多发性骨髓瘤患者的预后。

This combination may have potential to redefine treatment of multiple myeloma at or after first relapse, a setting where patients may benefit from novel therapies..

这种组合可能有可能在首次复发时或复发后重新定义多发性骨髓瘤的治疗，患者可能会从新疗法中受益。。

Similar to the results seen in the DREAMM-7 phase III head-to-head trial, in DREAMM-8 the belantamab mafodotin combination also resulted in clinically meaningful improvements consistently across secondary efficacy endpoints, showing that the belantamab mafodotin combination resulted in deeper and more durable responses compared to the bortezomib combination.

与DREAMM-7 III期头对头试验的结果类似，在DREAMM-8中，belantamab-mafodotin组合也在次要疗效终点上一致地导致临床上有意义的改善，表明belantamab-mafodotin组合导致更深和更持久的反应与硼替佐米组合相比。

Key improvements included rate of complete response (CR) or better (more than twofold improvement); minimal residual disease (MRD) negativity rate (nearly fivefold improvement); and duration of response (median not yet reached with the belantamab mafodotin combination versus 17.5 months with the bortezomib combination)..

关键改进包括完全缓解率（CR）或更好（超过两倍的改善）；最小残留病（MRD）阴性率（改善近五倍）；和反应持续时间（belantamab-mafodotin联合用药的中位数尚未达到，而硼替佐米联合用药的中位数为17.5个月）。。

Key and other secondary endpoint summaries are listed below.

关键和其他次要终点摘要如下所示。

Key and Other Secondary Endpoints

关键和其他次要端点

Endpoint

端点

belantamab mafodotin + pomalidomide and dexamethasone (BPd)(n= 155)

贝兰他单抗-马福多汀+泊马度胺和地塞米松（BPd）（n=155）

pomalidomide + bortezomib and dexamethasone (PVd)(n=147)

泊马度胺+硼替佐米和地塞米松（PVd）（n=147）

ORR (overall response rate), % (95% CI)

ORR（总体回应率），%（95%置信区间）

77% (70.0-83.7)

77% (70.0-83.7)

72% (64.1-79.2)

72% (64.1-79.2)

sCR (stringent complete   response), %

sCR（严格的完全响应），%

9%

9%

3%

3%

CR (complete response),   %

CR（完全响应），%

31%

31%

14%

14%

VGPR (very good partial    response), %

VGPR（非常好的部分响应），%

24%

24%

22%

22%

PR (partial response), %

PR（部分响应），%

14%

14%

34%

34%

CR or better rate (sCR+CR), % (95% CI)

CR或更高比率（sCR+CR），%（95%置信区间）

40% (32.2-48.2)

40% (32.2-48.2)

16% (10.7-23.3)

16% (10.7-23.3)

VGPR or better rate(sCR+CR+VGPR), % (95% CI)

VGPR或更高比率（sCR+CR+VGPR），%（95%CI）

64% (55.8-71.4)

64% (55.8-71.4)

38% (30.2-46.5)

38% (30.2-46.5)

MRD negativity rate* % (95% CI)

MRD阴性率*%（95%置信区间）

23.9% (17.4-31.4)

23.9% (17.4-31.4)

4.8% (1.9-9.6)

4.8% (1.9-9.6)

Duration of response (months), median (95% CI)

反应持续时间（月），中位数（95%置信区间）

NR (24.9-NR)

NR（24.9-NR）

17.5 months (12.1-26.4)

17.5个月（12.1-26.4）

Overall Survival**

总体生存率**

HR (95% CI)

人力资源（95%置信区间）

0.77 (0.53-1.14)

0.77 (0.53-1.14)

* Measured in patients with a sCR or CR.** Follow-up for OS is ongoing.NR: Not reached.

*在患有sCR或CR的患者中进行测量。*OS的随访正在进行中。NR：未达到。

Grade 3 or higher non-ocular adverse events (AEs) of clinical interest in the belantamab mafodotin combination versus bortezomib combination arms, respectively, included neutropenia (57% versus 39%; 42 patients/100 person-years in both arms); thrombocytopenia (38% versus 29%; 28 versus 31 patients/100 person-years); and pneumonia (17% versus 8%; 13 versus 8 patients/100 person-years)..

belantamab-mafodotin联合用药与硼替佐米联合用药组临床感兴趣的3级或更高级别非眼部不良事件（AE）分别包括中性粒细胞减少症（57%比39%；42例患者/100人年）；血小板减少症（38%比29%；28比31患者/100人年）；和肺炎（17%对8%；13对8患者/100人年）。。

Eye-related side effects, a known risk of treatment with belantamab mafodotin, were generally reversible, manageable with dose modifications, and led to low (9%) treatment discontinuation rates. Grade 3 or higher ocular adverse events occurred in 43% of patients receiving the belantamab mafodotin combination (Grade 3: 42%; Grade 4: 1%).

与眼睛相关的副作用是用belantamab-mafodotin治疗的已知风险，通常是可逆的，可以通过剂量调整来控制，并且导致治疗中断率低（9%）。接受belantamab-mafodotin联合治疗的患者中有43%发生3级或更高级别的眼部不良事件（3级：42%；4级：1%）。

Most commonly reported grade 3 or higher ocular symptoms included blurred vision (Grade 3: 17%; Grade 4: 0), dry eye (Grade 3: 8%: Grade 4: 0), and foreign body sensation in the eyes (Grade 3: 6%; Grade 4: 0). Fifty-one patients (34%) with a best corrected visual acuity (BCVA) of 20/25 or better in at least one eye at baseline had a worsening in both eyes to 20/50 or worse.

最常见的3级或更高级别眼部症状包括视力模糊（3级：17%；4级：0），干眼症（3级：8%：4级：0）和眼睛异物感（3级：6%；4级：0）。基线时至少一只眼睛的最佳矫正视力（BCVA）为20/25或更好的51名患者（34%）的双眼恶化至20/50或更差。

At the time of this analysis, the first occurrence of such events had improved in 92% of these patients, and resolved in 85%, with a median time to resolution of 57 days (range: 14-451 days)..

在进行分析时，这些事件的首次发生率在92%的患者中有所改善，在85%的患者中得到了解决，中位解决时间为57天（范围：14-451天）。。

Global health status quality of life (QOL), as measured by the EORTC-QLQ-C30 remained stable in both treatment arms over time, suggesting that treatment did not lead to any decline in overall health related QOL.

EORTC-QLQ-C30测量的全球健康状况生活质量（QOL）随着时间的推移在两个治疗组中保持稳定，表明治疗并未导致整体健康相关生活质量的任何下降。

The DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) clinical development programme continues to evaluate the potential of belantamab mafodotin in early lines of treatment and in combination with novel therapies and standard of care treatments. DREAMM-8 is the second phase III head-to-head belantamab mafodotin combination trial in second line and later treatment for multiple myeloma to report positive results.

DREAMM（推动多发性骨髓瘤治疗方法的卓越）临床开发计划继续评估belantamab-mafodotin在早期治疗中以及与新疗法和标准治疗相结合的潜力。DREAMM-8是多发性骨髓瘤二线和后期治疗的第二个III期头对头belantamab-mafodotin联合试验，报告阳性结果。

Positive findings from DREAMM-7, a phase III head-to-head trial evaluating belantamab mafodotin in combination with bortezomib and dexamethasone (BorDex) versus daratumumab plus BorDex in the same treatment setting, were presented1 at the ASCO Plenary Series on 6 February 2024, shared in an encore presentation at the 2024 ASCO Annual Meeting, and published in the New England Journal of Medicine..

DREAMM-7是一项III期头对头试验，评估belantamab-mafodotin联合硼替佐米和地塞米松（BorDex）与daratumumab加BorDex在同一治疗环境中的阳性结果，于2024年2月6日在ASCO全体会议上发表，并在2024年ASCO年会上发表在《新英格兰医学杂志》上。。

About DREAMM-8

关于DREAMM-8

The DREAMM-8 phase III clinical trial is a multicentre, open-label, randomised trial evaluating the efficacy and safety of belantamab mafodotin in combination with PomDex compared to a combination of bortezomib and PomDex in patients with relapsed/refractory multiple myeloma previously treated with at least one prior line of multiple myeloma therapy, including a lenalidomide-containing regimen, and who have documented disease progression during or after their most recent therapy.

DREAMM-8 III期临床试验是一项多中心，开放标签的随机试验，评估了belantamab-mafodotin联合PomDex与硼替佐米和PomDex联合治疗复发/难治性多发性骨髓瘤患者的疗效和安全性，这些患者先前至少接受过一种多发性骨髓瘤治疗，包括含来那度胺的方案，并且在最近的治疗期间或之后记录了疾病进展。

Compared to the patient population studied in the DREAMM-7 trial, patients in DREAMM-8 were more heavily pre-treated in that all had prior exposure to lenalidomide, 75% were refractory to lenalidomide, 25% had prior daratumumab exposure and of those most were daratumumab refractory..

与DREAMM-7试验中研究的患者人群相比，DREAMM-8患者的预处理程度更高，因为所有患者都曾接触过来那度胺，75%对来那度胺难治，25%曾接触过达拉木单抗，其中大多数是达拉木单抗难治性的。。

A total of 302 participants were randomised at a 1:1 ratio to receive either belantamab mafodotin plus PomDex, or bortezomib plus PomDex.

共有302名参与者以1:1的比例随机接受belantamab-mafodotin加PomDex或硼替佐米加PomDex。

The primary endpoint is PFS as per an independent review committee. Key secondary endpoints include OS, minimal residual disease negativity as assessed by next-generation sequencing, and duration of response. Other secondary endpoints include ORR, patient-reported quality of life outcomes, adverse events, eye exam findings, and laboratory investigations..

根据独立审查委员会的规定，主要终点是PFS。关键的次要终点包括OS，通过下一代测序评估的最小残留疾病阴性以及反应持续时间。其他次要终点包括ORR，患者报告的生活质量结果，不良事件，眼科检查结果和实验室检查。。

About multiple myeloma

关于多发性骨髓瘤

Multiple myeloma is the third most common blood cancer globally and is generally considered treatable but not curable.2,3 There are approximately 176,000 new cases of multiple myeloma diagnosed globally each year.4 Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.5.

多发性骨髓瘤是全球第三大最常见的血癌，通常被认为是可治疗但不可治愈的[2,3]。全球每年诊断出约176000例多发性骨髓瘤新病例[4]。由于多发性骨髓瘤通常难以治疗，因此需要对新疗法进行研究。

About Blenrep

关于Blenrep

Blenrep is an antibody-drug conjugate comprising a humanised B-cell maturation antigen monoclonal antibody conjugated to the cytotoxic agent auristatin F via a non-cleavable linker. The drug linker technology is licensed from Seagen Inc.; the monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa Inc., a member of the Kyowa Kirin Group..

Blenrep是一种抗体-药物缀合物，其包含通过不可切割的接头与细胞毒性剂auristatin F缀合的人源化B细胞成熟抗原单克隆抗体。drug linker技术由Seagen Inc.许可。；单克隆抗体是使用由协和麒麟集团成员BioWa Inc.许可的POTELLIGENT技术生产的。。

Refer to the Blenrep UK Summary of Product Characteristics6 for a full list of adverse events and the complete important safety information in the United Kingdom.

有关英国不良事件的完整列表和完整的重要安全信息，请参阅Blenrep UK产品特性摘要6。

GSK in oncology

葛兰素史克与肿瘤学

Oncology is an emerging therapeutic area for GSK where we are committed to maximising patient survival with a current focus on haematologic malignancies, gynaecologic cancers, and other solid tumours through breakthroughs in immuno-oncology and tumour-cell targeting therapies.

肿瘤学是GSK的一个新兴治疗领域，我们致力于通过免疫肿瘤学和肿瘤细胞靶向治疗的突破，最大限度地提高患者的生存率，目前专注于血液系统恶性肿瘤，妇科癌症和其他实体瘤。

About GSK

GSK

GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com.

葛兰素史克是一家全球性生物制药公司，旨在将科学、技术和人才团结起来，共同战胜疾病。更多信息请访问gsk.com。

Cautionary statement regarding forward-looking statements

关于前瞻性声明的警示声明

GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D “Risk factors” in GSK’s Annual Report on Form 20-F for 2023, and GSK’s Q1 Results for 2024..

葛兰素史克提醒投资者，葛兰素史克所作的任何前瞻性陈述或预测，包括本公告中所作的前瞻性陈述或预测，都存在风险和不确定性，可能导致实际结果与预测结果存在重大差异。这些因素包括但不限于葛兰素史克2023年20-F表年度报告第3.D项“风险因素”中所述的因素，以及葛兰素史克2024年第一季度的业绩。。

References

参考文献

GSK press release issued 05 February 2024. DREAMM-7 phase III trial shows Blenrep combination nearly tripled median progression-free survival versus standard of care combination in patients with relapsed/refractory multiple myeloma. Available at: https://www.gsk.com/en-gb/media/press-releases/dreamm-7-phase-iii-trial-shows-pfs-improvement-and-strong-os-trend-for-blenrep-combo-versus-soc-combo-in-multiple-myeloma/..

葛兰素史克新闻稿于2024年2月5日发布。DREAMM-7 III期试验显示，与复发/难治性多发性骨髓瘤患者的标准治疗组合相比，Blenrep组合的中位无进展生存期几乎增加了三倍。网址：https://www.gsk.com/en-gb/media/press-releases/dreamm-7-phase-iii-trial-shows-pfs-improvement-and-strong-os-trend-for-blenrep-combo-versus-soc-combo-in-multiple-myeloma/..

Sung H, Ferlay J, Siegel R, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660.

Sung H，Ferlay J，Siegel R等人，《2020年全球癌症统计：GLOBOCAN对185个国家36种癌症的全球发病率和死亡率的估计》。CA癌症J临床。2021年；71（3）：209-249。doi:10.3322/caac.21660。

Kazandjian D. Multiple myeloma epidemiology and survival: A unique malignancy. Semin Oncol. 2016;43(6):676–681.doi:10.1053/j.seminoncol.2016.11.004.

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