US FDA Expands Jemperli (Dostarlimab) Plus Chemotherapy Approval to All Adult Patients With Primary Advanced or Recurrent Endometrial Cancer as the First and Only Immuno-oncology-based Treatment to Show an Overall Survival Benefit
US FDA Expands Jemperli (Dostarlimab) Plus Chemotherapy Approval to All Adult Patients With Primary Advanced or Recurrent Endometrial Cancer as the First and Only Immuno-oncology-based Treatment to Show an Overall Survival Benefit
- Jemperli approval now includes MMRp/MSS tumours, which represent majority of endometrial cancer cases
- Jemperli plus chemotherapy demonstrated a statistically significant and clinically meaningful 31% reduction in risk of death versus chemotherapy alone
- Jemperli 的批准現在包括 MMRP/MSS 腫瘤,這些腫瘤佔子宮內膜癌病例的大多數
- 與單獨的化療相比,Jemperli聯合化療顯示死亡風險降低了31%,具有統計學意義且具有臨床意義
GSK plc (LSE/NYSE: GSK) today announced the US Food and Drug Administration (FDA) has approved Jemperli (dostarlimab) in combination with carboplatin and paclitaxel (chemotherapy) followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer. This approval broadens the previous indication for Jemperli plus chemotherapy to include patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumours who represent 70-75% of patients diagnosed with endometrial cancer and who have limited treatment options. The supplemental Biologics License Application (sBLA) supporting this expanded indication received Priority Review and was approved ahead of the Prescription Drug User Fee Act action date.
葛蘭素史克公司(倫敦證券交易所/紐約證券交易所代碼:GSK)今天宣佈,美國食品藥品監督管理局(FDA)已批准Jemperli(dostarlimab)與卡鉑和紫杉醇(化療)聯合用作單一藥物,用於治療原發性晚期或複發性子宮內膜癌的成年患者。該批准擴大了先前對Jemperli加化療的適應症,將錯配修復精通(mmRP)/微衛星穩定(MSS)腫瘤的患者包括在內,這些患者佔子宮內膜癌診斷患者的70-75%,且治療選擇有限。支持該擴展適應症的補充生物製劑許可申請(SBLa)獲得了優先審查,並在《處方藥使用者費用法》生效日期之前獲得批准。
Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: "Jemperli plus chemotherapy is the first and only immuno-oncology regimen to show significant and meaningful improvement in overall survival for adult patients with primary advanced or recurrent endometrial cancer regardless of biomarker status. We are thrilled this option is now available for more patients in the US, including the 70-75% with MMRp/MSS tumours where treatment options have been limited."
葛蘭素史克高級副總裁兼研發腫瘤學全球負責人赫沙姆·阿卜杜拉表示:“Jemperli plus化療是第一個也是唯一一種無論生物標誌物狀態如何,對原發性晚期或複發性子宮內膜癌的成年患者的總體存活率都有顯著而有意義的改善的免疫腫瘤學方案。我們很高興美國現在有更多的患者可以使用這個選項,包括70-75%的MMRP/MSS腫瘤患者,他們的治療選擇有限。”
Today's expanded approval is based on results from dual primary endpoints of investigator-assessed progression-free survival (PFS) and overall survival (OS) from Part 1 of the RUBY phase III trial. RUBY Part 1 is the only clinical trial in this setting to show a statistically significant OS benefit in the full population of patients with primary advanced or recurrent endometrial cancer, demonstrating a 31% reduction in risk of death (HR: 0.69; 95% CI: 0.54–0.89) compared to chemotherapy alone.
今天的擴大批准是基於研究者評估的無進展生存期(PFS)和RUBY III期試驗第1部分的總生存期(OS)這兩個主要終點的結果。RUBY 第 1 部分是該環境中唯一一項顯示所有原發性晚期或複發性子宮內膜癌患者的操作系統益處具有統計學意義的臨床試驗,表明與單獨的化療相比,死亡風險降低了 31%(HR:0.69;95% 置信區間:0.54—0.89)。
At the 2.5-year landmark, 61% (95% CI: 54-67) of patients in the Jemperli plus chemotherapy group compared to 49% (95% CI: 43-55) in the chemotherapy group were alive. In addition, a 16.4-month improvement in median OS was observed with Jemperli plus chemotherapy versus chemotherapy alone (44.6 months [95% CI: 32.6–NR] vs. 28.2 months [95% CI: 22.1–35.6], respectively). The median duration of follow-up was more than three years.1 The safety and tolerability analysis from RUBY Part 1 showed a safety profile for Jemperli and carboplatin-paclitaxel that was generally consistent with the known safety profiles of the individual agents. The most common treatment-emergent adverse events (≥ 20%) in patients receiving Jemperli plus chemotherapy were nausea, alopecia, fatigue, peripheral neuropathy, anaemia, arthralgia, constipation, diarrhoea, myalgia, rash, hypomagnesemia, decreased appetite, peripheral sensory neuropathy and vomiting.
在2.5年的里程碑上,Jemperli加化療組中有61%(95%置信區間:54-67)的患者還活着,而化療組的這一比例爲49%(95%置信區間:43-55)。此外,與單獨使用化療相比,Jemperli加化療的操作系統中位數改善了16.4個月(44.6個月 [95% 置信區間:32.6—NR] 對比28.2個月 [95% 置信區間:22.1—35.6])。隨訪時間中位數超過三年。1 RUBY 第 1 部分的安全性和耐受性分析顯示,Jemperli 和卡鉑-紫杉醇的安全性概況與個別藥物的已知安全性概況基本一致。在接受Jemperli加化療的患者中,最常見的治療緊急不良事件(≥ 20%)是噁心、脫髮、疲勞、周圍神經病變、貧血、關節痛、便秘、腹瀉、肌痛、皮疹、低鎂血癥、食慾下降、周圍感覺神經病變和嘔吐。
Matthew Powell, MD, Chief, Division of Gynecologic Oncology, Washington University School of Medicine, and US principal investigator of the RUBY trial said: "The initial approval of Jemperli plus chemotherapy was practice-changing for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer and today's expanded approval will offer even more patients the opportunity for improved outcomes. This is the only immuno-oncology treatment regimen that has shown a statistically significant overall survival benefit for the full patient population, which is a meaningful step forward in treating this challenging cancer."
華盛頓大學醫學院婦科腫瘤學部主任、美國RUBY試驗首席研究員馬修·鮑威爾醫學博士說:“Jemperli加化療的初步批准改變了DMMR/MSI-H原發性晚期或複發性子宮內膜癌患者的做法,今天的擴大批准將爲更多患者提供改善預後的機會。這是唯一一種在整個患者群體中顯示出具有統計學意義的總體存活益處的免疫腫瘤學治療方案,這是在治療這種具有挑戰性的癌症方面向前邁出的有意義的一步。”
Adrienne Moore, Survivor, Founding Member and President of Endometrial Cancer Action Network for African-Americans (ECANA) said: "With this expanded approval for Jemperli plus chemotherapy, GSK is bringing a much-needed new treatment regimen to the endometrial cancer community that may help patients with primary advanced or recurrent endometrial cancer live longer, providing hope to patients and their families. Survivors and advocates should be excited by today's news and especially delighted that this approval means that more patients in the US who are diagnosed with endometrial cancer will have a new treatment option."
倖存者、非裔美國人子宮內膜癌行動網絡(ECANA)創始成員兼主席艾德麗安·摩爾說:“隨着對Jemperli plus化療的批准範圍的擴大,葛蘭素史克正在爲子宮內膜癌界帶來一種急需的新治療方案,可以幫助原發性晚期或複發性子宮內膜癌患者延長壽命,爲患者及其家人帶來希望。倖存者和倡導者應該對今天的新聞感到興奮,尤其高興的是,這一批准意味着美國有更多被診斷出患有子宮內膜癌的患者將有新的治療選擇。”
About endometrial cancer
關於子宮內膜癌
Endometrial cancer is found in the inner lining of the uterus, known as the endometrium. Endometrial cancer is the most common gynaecologic cancer in developed countries,2 with an estimated 1.6 million people living with active disease at any stage and 417,000 new cases reported each year worldwide.3 Incidence rates are expected to rise by approximately 40% between 2020 and 2040.4 Approximately 15-20% of patients with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis.5 Among patients with primary advanced or recurrent endometrial cancer, approximately 70-75% have MMRp/MSS tumours.6
子宮內膜癌存在於子宮內膜,即子宮內膜。子宮內膜癌是發達國家最常見的婦科癌症,2 估計在任何階段都有160萬人患有活性疾病,全球每年報告41.7萬例新發病例。3 預計在2020年至2044年之間,發病率將上升約40%。0.4 在診斷時約有15-20%的子宮內膜癌患者將被診斷爲晚期疾病。5 在原發性晚期或複發性子宮內膜的患者中大約 70-75% 的癌症有 MMRP/MSS 腫瘤。6
About RUBY
關於 RUBY
RUBY is a two-part global, randomised, double-blind, multicentre phase III trial of patients with primary advanced or recurrent endometrial cancer. Part 1 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab versus carboplatin-paclitaxel plus placebo followed by placebo. Part 2 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib versus placebo plus carboplatin-paclitaxel followed by placebo.
RUBY 是一項由兩部分組成的全球性、隨機、雙盲、多中心三期試驗,針對原發性晚期或複發性子宮內膜癌患者。第一部分是評估多斯達利單抗加卡鉑-紫杉醇,其次是多斯塔利單抗對比卡鉑-紫杉醇加安慰劑,然後是安慰劑。第二部分是評估多斯達利單抗加卡鉑-紫杉醇,其次是多斯塔利單抗加尼拉帕尼對比安慰劑加卡鉑-紫杉醇然後是安慰劑。
In Part 1, the dual-primary endpoints are investigator-assessed PFS based on the Response Evaluation Criteria in Solid Tumours v1.1 and OS. The statistical analysis plan included pre-specified analyses of PFS in the mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) and overall populations and OS in the overall population. Pre-specified exploratory analyses of PFS and OS in the MMRp/MSS population and OS in the dMMR/MSI-H populations were also performed. RUBY Part 1 included a broad population, including histologies often excluded from clinical trials and had approximately 10% of patients with carcinosarcoma and 20% with serous carcinoma.
在第 1 部分中,雙主要終點是研究人員根據實體瘤反應評估標準 v1.1 和操作系統評估的 PFS。統計分析計劃包括對失配修復缺陷(dmMR)/微衛星不穩定性高(MSI-H)中的PFS以及總人群中的總種群和操作系統進行預先指定的分析。還對MMRP/MSS人群中的PFS和OS以及DMMR/MSI-H人群中的操作系統進行了預先指定的探索性分析。RUBY 第 1 部分涵蓋了廣泛的人群,包括通常被排除在臨床試驗之外的組織結構,大約有 10% 的癌肉瘤患者和 20% 的漿液性癌患者。
In Part 2, the primary endpoint is investigator-assessed PFS in the overall population, followed by PFS in the MMRp/MSS population, and OS in the overall population is a key secondary endpoint. Additional secondary endpoints in Part 1 and Part 2 include PFS per blinded independent central review, PFS2, overall response rate, duration of response, disease control rate, patient-reported outcomes, and safety and tolerability.
在第 2 部分中,主要終點是研究人員評估的總體人群中的 PFS,其次是 MMRP/MSS 人群中的 PFS,總人群中的 OS 是關鍵的次要終點。第1部分和第2部分中的其他次要終點包括每個盲人獨立中心審查的PFS、PFS2、總體緩解率、反應持續時間、疾病控制率、患者報告的結果以及安全性和耐受性。
RUBY is part of an international collaboration between the European Network of Gynaecological Oncological Trial groups (ENGOT), a research network of the European Society of Gynaecological Oncology (ESGO) that consists of 22 trial groups from 31 European countries that perform cooperative clinical trials, and the GOG Foundation, a non-profit organisation dedicated to transforming the standard of care in gynaecologic oncology.
RUBY是歐洲婦科腫瘤學試驗小組網絡(ENGOT)與致力於改變婦科腫瘤學護理標準的非營利組織GOG基金會之間的國際合作的一部分,該網絡是歐洲婦科腫瘤學會(ESGO)的研究網絡,由來自31個歐洲國家的22個進行合作臨床試驗的試驗小組組成。
About Jemperli (dostarlimab)
關於 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是一種程序性死亡受體-1(PD-1)阻斷抗體,是葛蘭素史克正在進行的基於免疫腫瘤學的研發計劃的支柱。一項強有力的臨床試驗計劃包括單獨對Jemperli進行研究,以及與婦科、結直腸和肺癌以及有機會取得轉型結果的其他療法聯合研究。
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 MMRp/MSS and dMMR/MSI-H tumours. 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. 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. Continued approval for this indication in solid tumours may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
在美國,Jemperli應與卡鉑和紫杉醇聯合使用,其次是Jemperli作爲治療原發性晚期或複發性子宮內膜癌的成年患者的單一藥物。這包括患有 MMRP/MSS 和 DMMR/MSI-H 腫瘤的患者。Jemperli還被批准爲dmMR複發性或晚期子宮內膜癌成年患者的單一藥物,該藥物由美國食品藥品管理局批准的測試確定,該藥物在任何環境下均已按照或遵循先前的含鉑療法取得進展,並且不適合治療性手術或放射治療。此外,根據美國食品藥品管理局批准的試驗,在美國,複發性或晚期實體瘤患者,在先前的治療或之後取得了進展,並且沒有令人滿意的替代治療選擇,Jemperli適用於複發性或晚期實體瘤患者。後一種適應症在美國獲得批准,這是基於腫瘤反應率和反應持久性的加速批准的。該適應症在實體瘤中的持續批准可能取決於確認性試驗中對臨床益處的驗證和描述。
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.
根據2014年3月簽署的合作和獨家許可協議,Jemperli由AnaptysBio, Inc.發現,並被許可給TESARO, Inc.。根據該協議,葛蘭素史克負責正在進行的研究、開發、商業化和生產 Jemperli和cobolimab(GSK4069889),一種Tim-3拮抗劑。
Please see accompanying US Prescribing Information.
請參閱隨附的美國處方信息。
GSK in oncology
GSK 在腫瘤學領域的應用
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.
腫瘤學是GsK的新興治療領域,我們致力於通過免疫腫瘤學和腫瘤細胞靶向療法方面的突破,最大限度地提高患者的存活率,目前的重點是血液惡性腫瘤、婦科癌和其他實體瘤。
About GSK
關於葛蘭素史克
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.
葛蘭素史克是一家全球生物製藥公司,其宗旨是聯合科學、技術和人才,共同戰勝疾病。要了解更多信息,請訪問 gsk.com。