GSK plc (LSE/NYSE: GSK) announced today that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for Jemperli (dostarlimab) for the treatment of patients with locally advanced mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) rectal cancer. The Breakthrough Therapy Designation aims to expedite the development and review of drugs with the potential to treat a serious condition and where preliminary clinical evidence may indicate substantial improvement over currently available therapy.1 This is the second regulatory designation for dostarlimab in locally advanced dMMR/MSI-H rectal cancer, following Fast Track designation for the same patient population in January 2023.2.

葛兰素史克股份有限公司（LSE/NYSE:GSK）今天宣布，美国食品和药物管理局（FDA）已批准Jemperli（dostarlimab）突破性治疗指定，用于治疗局部晚期错配修复缺陷（dMMR）/微卫星不稳定性高（MSI-H）直肠癌患者。突破性治疗指定旨在加速开发和审查有可能治疗严重疾病的药物，初步临床证据可能表明比目前可用的治疗方法有实质性改善[1]。这是在2023年1月对同一患者群体进行快速指定后，在局部晚期dMMR/MSI-H直肠癌中对dostarlimab进行的第二次监管指定。

Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: “Today’s designation, which is based on the unprecedented 100% clinical complete response rate of dostarlimab reported to date, supports a path to help change the treatment paradigm for patients with locally advanced dMMR/MSI-H rectal cancer, who face long-term adverse quality-of-life effects.

葛兰素史克研发全球肿瘤学负责人高级副总裁Hesham Abdullah表示：“今天的指定是基于迄今为止报道的前所未有的100%临床完全缓解率，支持一条有助于改变局部晚期dMMR/MSI-H直肠癌患者治疗模式的途径，这些患者面临长期不良生活质量影响。

Our registrational AZUR-1 trial is continuing to study dostarlimab in this patient population.”.

我们的注册AZUR-1试验正在继续研究该患者人群中的dostarlimab。”。

The US FDA’s Breakthrough Therapy Designation is supported by preliminary clinical evidence from the ongoing phase II GSK supported collaborative study with Memorial Sloan Kettering Cancer Center. In frontline locally advanced dMMR rectal cancer, the trial has shown an unprecedented 100% clinical complete response (cCR) in all 42 patients who completed treatment with dostarlimab, defined as no evidence of tumours as assessed by magnetic resonance imaging, endoscopy, PET scan and digital rectal exam.

美国FDA的突破性治疗指定得到了GSK与纪念斯隆·凯特琳癌症中心正在进行的第二阶段合作研究的初步临床证据的支持。在一线局部晚期dMMR直肠癌中，该试验在所有42名完成dostarlimab治疗的患者中显示出前所未有的100%临床完全缓解（cCR），定义为通过磁共振成像，内窥镜检查，PET扫描和数字直肠检查评估没有肿瘤证据。

In the first 24 patients evaluated, a sustained cCR with a median follow-up of 26.3 months (95% CI: 12.4-50.5) was observed. The safety and tolerability profile of dostarlimab was generally consistent with the known safety profile of the agent. No adverse events of grade 3 or higher were reported in this trial.3 The trial continues to evaluate enrolled patients.

在评估的前24名患者中，观察到持续的cCR，中位随访时间为26.3个月（95%CI:12.4-50.5）。dostarlimab的安全性和耐受性概况通常与该药物的已知安全性概况一致。该试验未报告3级或更高级别的不良事件。3该试验继续评估入选患者。

GSK’s ongoing phase II registrational AZUR-1 trial in locally advanced dMMR/MSI-H rectal cancer aims to confirm the findings of this supported collaborative study..

GSK正在进行的局部晚期dMMR/MSI-H直肠癌II期注册AZUR-1试验旨在证实这项支持的合作研究的结果。。

The current standard of care for patients with dMMR/MSI-H locally advanced rectal cancer is initial treatment with chemotherapy plus radiation followed by surgery to remove the tumour along with portions of the intestine and/or surrounding tissue.4 This results in initial positive outcomes for most patients, but nearly one-third ultimately die from cancer that has spread to other parts of the body (distant metastasis).5 Additionally, the surgery and chemoradiotherapy associated with standard of care can lead to long-term negative impact on quality-of-life, including bowel, urinary and sexual dysfunction, secondary cancers and infertility.2.

目前对dMMR/MSI-H局部晚期直肠癌患者的护理标准是化疗加放疗，然后进行手术切除肿瘤以及部分肠道和/或周围组织[4]。这导致大多数患者的初始积极结果，但近三分之一的患者最终死于已扩散到身体其他部位的癌症（远处转移）[5]。此外，与标准护理相关的手术和放化疗可能对生活质量产生长期负面影响，包括肠，泌尿和性功能障碍，继发性癌症和不孕症。

Dostarlimab is not approved anywhere in the world for the frontline treatment of locally advanced dMMR/MSI-H rectal cancer.

Dostarlimab在世界任何地方都没有被批准用于局部晚期dMMR/MSI-H直肠癌的一线治疗。

About dMMR/MSI-H rectal cancer

关于dMMR/MSI-H直肠癌

Rectal cancer is a form of cancer that starts in the rectum, the final section of the large intestine, and is often categorised as part of a group of cancers called colorectal cancer. Colorectal cancer is the third most commonly diagnosed cancer in the world.6 In the US, it is estimated that approximately 46,220 individuals are diagnosed annually with rectal cancer.7 Approximately 5-10% of all rectal cancers are dMMR/MSI-H, meaning that they contain abnormalities that affect the proper repair of DNA when copied in a cell.8 Mismatch repair deficient status is a biomarker that has been shown to predict response to immune checkpoint blockade with PD-1 therapy.9,10 Tumours with this biomarker are most commonly found in endometrial, colorectal and other gastrointestinal cancers but may also be found in other solid tumours.11-14.

直肠癌是一种始于直肠（大肠的最后一部分）的癌症，通常被归类为一组称为结直肠癌的癌症的一部分。结直肠癌是世界上第三大最常被诊断的癌症[6]。在美国，估计每年约有46220人被诊断出患有直肠癌[7]。所有直肠癌中约有5-10%是dMMR/MSI-H，这意味着它们含有影响DNA在细胞中复制时正确修复的异常[8]。错配修复缺陷状态是一种生物标志物，已被证明可以预测PD-1治疗对免疫检查点阻断的反应[9,10]。这种生物标志物的肿瘤最常见于子宫内膜癌，结直肠癌和其他胃肠道癌，但也可能在其他实体瘤中发现[11-14]。

About Jemperli (dostarlimab)

关于Jemperli（Dostarlimab）

Jemperli, a programmed death receptor-1 (PD-1)-blocking antibody, is the backbone of GSK’s ongoing immuno-oncology-based research and development programme. A robust clinical trial programme includes studies of Jemperli alone and in combination with other therapies in gynaecologic, colorectal and lung cancers, as well as where there are opportunities for transformational outcomes..

Jemperli是一种程序性死亡受体-1（PD-1）阻断抗体，是GSK正在进行的基于免疫肿瘤学的研究和开发计划的骨干。一个强大的临床试验计划包括单独研究Jemperli，并与妇科，结直肠癌和肺癌的其他疗法相结合，以及有机会取得变革性结果的研究。。

In the US, Jemperli is indicated in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer. This includes patients with mismatch repair proficient/microsatellite stable (MMRp/MSS) and dMMR/MSI-H tumours.

在美国，Jemperli与卡铂和紫杉醇联合使用，其次是Jemperli作为单一药物治疗成人原发性晚期或复发性子宫内膜癌患者。这包括错配修复熟练/微卫星稳定（MMRp/MSS）和dMMR/MSI-H肿瘤的患者。

Jemperli is also approved as a single agent for adult patients with dMMR recurrent or advanced endometrial cancer, as determined by a US FDA-approved test, that has progressed on or following a prior platinum-containing regimen in any setting and are not candidates for curative surgery or radiation.

Jemperli也被批准作为dMMR复发或晚期子宫内膜癌成年患者的单一药物，这是由美国FDA批准的测试确定的，该药物在任何情况下都在先前的含铂方案上或之后取得了进展，并且不适合进行根治性手术或放疗。

Additionally, Jemperli is indicated in the US for patients with dMMR recurrent or advanced solid tumours, as determined by a US FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. The latter indication is approved in the US under accelerated approval based on tumour response rate and durability of response.

此外，Jemperli在美国适用于dMMR复发或晚期实体瘤患者，这是由美国FDA批准的测试确定的，这些患者在之前的治疗或之后已经取得进展，并且没有令人满意的替代治疗选择。后一种适应症在美国根据肿瘤反应率和反应持久性加速批准。

Continued approval for this indication in solid tumours may be contingent upon verification and description of clinical benefit in a confirmatory trial(s)..

在实体瘤中继续批准这种适应症可能取决于验证性试验中临床益处的验证和描述。。

Jemperli was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc., under a collaboration and exclusive license agreement signed in March 2014. Under this agreement, GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of Jemperli and cobolimab (GSK4069889), a TIM-3 antagonist. .

Jemperli‡是由AnaptysBio，Inc.发现的，并根据2014年3月签署的合作和独家许可协议授权给TESARO，Inc。根据该协议，葛兰素史克（GSK）负责对TIM-3拮抗剂Jemperli和cobolimab（GSK4069889）进行持续的研究，开发，商业化和生产。 .

Important Information for Jemperli in the EU

Jemperli在欧盟的重要信息

Jemperli is indicated:

Jemperli表示：

in combination with carboplatin and paclitaxel, for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer and who are candidates for systemic therapy;

联合卡铂和紫杉醇治疗错配修复缺陷型（dMMR）/微卫星不稳定性高（MSI-H）原发性晚期或复发性子宫内膜癌的成年患者，以及全身治疗的候选者；

as monotherapy for treating adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen.

作为单一疗法，用于治疗错配修复缺陷型（dMMR）/微卫星不稳定性高（MSI-H）复发或晚期子宫内膜癌的成年患者，这些患者在先前使用含铂方案治疗时或之后已经进展。

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。。