– MANEUVER 研究達(dá)到主要終點(diǎn)，第 25 周的客觀緩解率 （ORR） 為54.0%，而安慰劑組為3.2%（p<0.0001）。

       – 在所有關(guān)鍵次要終點(diǎn)（包括疼痛和僵硬）方面也取得了有統(tǒng)計(jì)學(xué)意義和臨床意義的顯著改善。

       – 每日一次口服匹米替尼的治療耐受性良好，因治療相關(guān)不良事件而終止治療的比例極低。

       – 匹米替尼1b期最新研究結(jié)果顯示，其最佳客觀緩解率達(dá)85%，中位治療持續(xù)時(shí)間達(dá)到20個(gè)月。

       11月12日，和譽(yù)醫(yī)藥宣布根據(jù)獨(dú)立盲審委員會(huì)（BIRC）的RECIST v1.1標(biāo)準(zhǔn)，評(píng)估匹米替尼治療腱鞘巨細(xì)胞瘤（TGCT）的3期MANEUVER研究在第25周客觀緩解率（ORR）方面取得了統(tǒng)計(jì)學(xué)意義上的顯著改善，達(dá)到54.0%，而安慰劑為3.2%。

       值得注意的是，該研究還表明，匹米替尼治療對(duì)與TGCT重要患者臨床結(jié)果相關(guān)的次要終點(diǎn)有統(tǒng)計(jì)學(xué)意義和臨床意義的顯著改善，這些次要終點(diǎn)包括按數(shù)字評(píng)定量表測(cè)定僵硬程度（NRS；與基線相比，平均變化為-3.00，安慰劑組為- 0.57，p<0.0001），和按簡(jiǎn)明疼痛量表測(cè)定疼痛程度（BPI；-2.32對(duì)0.23的基線平均變化，p<0.0001）。MANEUEVER研究第1部分的詳細(xì)療效和安全性數(shù)據(jù)將在即將召開的醫(yī)學(xué)會(huì)議上公布。

       在 MANEUVER 研究中，匹米替尼展現(xiàn)出良好的的耐受性，安全性數(shù)據(jù)與先前報(bào)告的數(shù)據(jù)一致，未觀察到膽汁淤積性肝毒性發(fā)生。治療中匹米替尼組出現(xiàn)的不良事件 （TEAE）導(dǎo)致治療終止和劑量下調(diào)的患者分別是1.6%（1名）和7.9%（5名）。

       “腱鞘巨細(xì)胞瘤往往多發(fā)于年輕人。這種罕見的良性腫瘤生長(zhǎng)在關(guān)節(jié)內(nèi)部和周圍，主要影響處于工作年齡的年輕人和中年人。腱鞘巨細(xì)胞瘤主要表現(xiàn)為關(guān)節(jié)腫脹、疼痛、僵硬和活動(dòng)受限，會(huì)嚴(yán)重影響日?；顒?dòng)能力，限制患者的工作和社交生活。其一般需要通過(guò)手術(shù)進(jìn)行治療，但是術(shù)后的高復(fù)發(fā)率以及反復(fù)手術(shù)可能帶來(lái)的并發(fā)癥給患者帶來(lái)了巨大挑戰(zhàn)，因此迫切需要能夠控制腫瘤生長(zhǎng)的系統(tǒng)性療法。” 北京積水潭醫(yī)院骨與軟組織腫瘤診療中心主任牛曉輝教授表示，“基于MANEUVER研究的最新數(shù)據(jù)以及匹米替尼對(duì)CSF-1R的高選擇性和有效抑制作用，加上每日一次的口服給藥方式還有助于提高患者的長(zhǎng)期依從性，匹米替尼有可能為腱鞘巨細(xì)胞瘤患者建立一種新的治療模式。

       和譽(yù)醫(yī)藥董事長(zhǎng)兼CEO徐耀昌博士表示：“MANEUVER 是一項(xiàng)具有里程碑意義的全球性研究。它是首個(gè)在多個(gè)地區(qū)以均衡比例招募亞洲和西方腱鞘巨細(xì)胞瘤患者的全球性試驗(yàn)。這樣就可以進(jìn)行詳細(xì)的結(jié)果比較，有助于更深入地了解不同人群的疾病特征和潛在的反應(yīng)差異。匹米替尼代表了新興CSF-1R抑制劑類別的關(guān)鍵進(jìn)展，有望為全球的腱鞘巨細(xì)胞瘤患者提供新型口服小分子藥物治療方案。我們期待和默克團(tuán)隊(duì)緊密合作，共同推動(dòng)匹米替尼的注冊(cè)申報(bào)，讓匹米替尼成為系統(tǒng)性治療腱鞘巨細(xì)胞瘤的首選方案！”

       2023年12月，和譽(yù)醫(yī)藥與總部位于德國(guó)達(dá)姆施塔特的領(lǐng)先科技公司默克醫(yī)藥健康達(dá)成許可協(xié)議，授予其在中國(guó)大陸、中國(guó)香港、中國(guó)澳門和中國(guó)臺(tái)灣地區(qū)的獨(dú)家商業(yè)化許可，以及匹米替尼全球商業(yè)權(quán)利的獨(dú)家選擇權(quán)。

       “對(duì)于主要由CSF-1過(guò)表達(dá)引起的TGCT，臨床上迫切需要有效且耐受性良好的系統(tǒng)性治療，該疾病會(huì)導(dǎo)致關(guān)節(jié)組織增厚和過(guò)度生長(zhǎng)，嚴(yán)重影響患者的生活。MANEUVER的III期數(shù)據(jù)證實(shí)了和譽(yù)醫(yī)藥I期研究的結(jié)果，表明pimicotinib靶向CSF-1有望為患者提供新的治療選擇。我們將與和譽(yù)醫(yī)藥合作并審閱該研究數(shù)據(jù)，準(zhǔn)備和中國(guó)的監(jiān)管機(jī)構(gòu)分享研究結(jié)果，我們的共同目標(biāo)是盡快將pimicotinib帶給有需要的患者。”默克醫(yī)藥健康全球研發(fā)負(fù)責(zé)人兼首席醫(yī)學(xué)官Danny Bar-Zohar表示。

       關(guān)于MANEUVER

       MANEUVER 關(guān)鍵研究是一項(xiàng)由三部分組成的、隨機(jī)、雙盲、安慰劑對(duì)照臨床3 期研究，旨在評(píng)估匹米替尼對(duì)符合接受系統(tǒng)性治療條件且既往未接受過(guò)抗 CSF1/CSF1R 治療的 TGCT 患者中的療效和安全性。該研究正在中國(guó)（45 例患者）、歐洲（28 例）、美國(guó)和加拿大（21 例）開展。

       在第1部分雙盲研究階段，94名患者 以 2：1 的比例隨機(jī)接受 50 mg QD 的 匹米替尼（n=63）或安慰劑 （n=31）治療24 周。其主要終點(diǎn)是在意向治療人群中第 25 周時(shí)的客觀緩解率 （ORR），由獨(dú)立盲審委員會(huì)基于實(shí)體瘤反應(yīng)評(píng)估標(biāo)準(zhǔn) （RECIST）1.1 版進(jìn)行評(píng)估。次要終點(diǎn)包括基于腫瘤體積的評(píng)分、主動(dòng)關(guān)節(jié)活動(dòng)度、數(shù)字評(píng)定量表（NRS）測(cè)定的僵硬程度、簡(jiǎn)要疼痛量表（BPI）測(cè)定的疼痛程度和 PROMIS 身體功能評(píng)估。

       在第 1 部分雙盲研究完成后，符合條件的患者可以繼續(xù)接受開放標(biāo)簽的第 2 部分，完成最長(zhǎng) 24 周的治療。完成第 2 部分的患者可以進(jìn)入開放標(biāo)簽延長(zhǎng)期（第 3 部分）以進(jìn)行延長(zhǎng)治療和安全隨訪。

       匹米替尼治療腱鞘巨細(xì)胞瘤 1b期研究的最新長(zhǎng)期隨訪結(jié)果

       和譽(yù)醫(yī)藥還公布了評(píng)估匹米替尼對(duì)TGCT患者安全性和有效性的1期開放標(biāo)簽多中心研究的最新結(jié)果。題為“匹米替尼（ABSK021）在腱鞘巨細(xì)胞瘤（TGCT）中的長(zhǎng)期療效和安全性概況：1b期研究更新報(bào)告”的壁報(bào)將在2024年11月13日至16日于美國(guó)圣地亞哥舉行的結(jié)締組織腫瘤學(xué)會(huì)（CTOS）年會(huì)上展示。

       截至2024年6月30日，此前報(bào)告的42名50 mg劑量組患者的數(shù)據(jù)更新如下：

       - 根據(jù)獨(dú)立審查委員會(huì)（IRC）的RECIST v1.1評(píng)估，最佳ORR為85.0%。中位治療持續(xù)時(shí)間為20.67個(gè)月（0.5, 30.1），54.8%的患者持續(xù)治療時(shí)間≥18個(gè)月，38.1%的患者持續(xù)治療時(shí)間≥24個(gè)月?；贙aplan-Meier評(píng)估，中位緩解持續(xù)時(shí)間尚未達(dá)到（NR），69.0%的患者仍在接受治療。在長(zhǎng)期治療過(guò)程中，觀察到腫瘤持續(xù)縮小、疼痛程度和僵硬緩解程度以及關(guān)節(jié)活動(dòng)能力的逐步改善。

       - 總體安全性狀況與既往報(bào)道保持一致，長(zhǎng)期隨訪未發(fā)現(xiàn)特殊的不良事件。

       - 未觀察到膽汁淤積性肝毒性發(fā)生。

       Pimicotinib Significantly Improved Outcomes for Patients with Tenosynovial Giant Cell Tumor in a Global Phase III Trial

       – The MANEUVER study met the primary endpoint with an objective response rate (ORR) at week 25 of 54.0% compared with 3.2% for placebo (p< 0.0001 ) –

       – Statistically significant and clinically meaningful improvements also seen in all key secondary endpoints, including pain and stiffness -

       – Treatment with oral, once-daily pimicotinib was well-tolerated, with very low rates of discontinuation due to treatment-related adverse events –

       – Updated results from Phase 1b study of pimicotinib demonstrated best ORR of 85% with median treatment duration of 20 months –

       Abbisko today announced that the Phase 3 MANEUVER study evaluating pimicotinib in the treatment of tenosynovial giant cell tumor (TGCT) achieved statistically significant improvements in objective response rate (ORR) at Week 25 of 54.0%, compared with 3.2% for placebo (p< 0.0001) based on RECIST v1.1 per Blinded Independent Review Committee（BIRC）.

       Notably, the study also showed that treatment with pimicotinib provided statistically significant and clinically meaningful improvements in secondary endpoints associated with important patient outcomes in TGCT, including stiffness by Numeric Rating Scale (NRS; -3.00 mean change from baseline vs. -0.57 for placebo, p<0.0001) and pain by Brief Pain Inventory (BPI; -2.32 vs. 0.23 mean change from baseline, p<0.0001). Further efficacy and safety data from Part 1 of the MANEUEVER study will be presented at an upcoming medical conference.

       In MANEUVER, pimicotinib was well-tolerated, and the safety profile was consistent with prior reported data, with no evidence of cholestatic hepatotoxicity. Treatment-emergent adverse events (TEAEs) leading to treatment discontinuation occurred in 1.6% (n=1) of patients treated with pimicotinib; TEAEs leading to dose reduction occurred in 7.9% (n=5) of pimicotinib-treated patients.

       “TGCT tends to be a disease of the young. This rare, benign tumor that grows in and around the joints primarily affects young and middle-aged adults in their working years. The swelling, pain, stiffness and limited mobility caused by the disease can have a significant impact on the ability to perform daily activities, limiting patients’ work and social lives. Treatment often involves surgery, yet the high recurrence rate and potential complications from repeated surgical interventions can be very challenging for patients to deal with, creating an urgent need for systemic therapy that could control tumor growth,” said Professor Niu Xiaohui, Director of the Bone and Soft Tissue Tumour Diagnosis and Research Centre at Beijing Jishuitan Hospital. “Based on these new data from the MANEUVER study, together with once-daily oral administration that may promote long-term adherence and pimicotinib’s selective inhibition of CSF-1R, this investigational medicine has the potential to establish a new treatment paradigm for patients with TGCT .”

       Yaochang Xu, Chairman and CEO of Abbisko Therapeutics, said, “As the first global trial to enroll both Asian and Western patients with TGCT in balanced proportions across multiple regions, MANEUVER is a landmark global study that allows for detailed outcome comparisons. This can facilitate a deeper understanding of disease characteristics and potential similar response across different populations. This unique study shows that pimicotinib has the potential to provide a novel oral small molecule therapy option for TGCT patients, representing a key advancement within the emerging class of CSF-1R inhibitors. We look forward to collaborating with Merck as we pursue registration of pimicotinib as the first therapy option indicated for the systemic treatment of TGCT in China.”

       In December 2023, Abbisko Therapeutics entered into a licensing agreement granting Merck, a leading science and technology company headquartered in Darmstadt, Germany, an exclusive license to commercialize pimicotinib in Chinese mainland, Hong Kong, Macau, and Taiwan, as well as an exclusive option for global commercial rights of pimicotinib.

       “There is a tremendous unmet need for effective, well-tolerated systemic treatment for TGCT, a disease primarily caused by CSF-1 overexpression that leads to joint tissue thickening and overgrowth, severely impacting patients’ lives. These Phase III data from MANEUVER confirm results of Abbisko’s Phase I study, indicating that targeting CSF-1R with pimicotinib has the potential to offer a new treatment option for patients. As we work with Abbisko to review the data from this study and prepare to share it with regulators in China, we are focused on our shared goal of bringing pimicotinib to patients in need,” said Danny Bar-Zohar, Global Head of Research & Development and Chief Medical Officer for the Healthcare business sector of Merck.

       About MANEUVER

       The pivotal Phase 3 MANEUVER study is a three-part, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of pimicotinib in patients with TGCT who are eligible for systemic therapy and who have not received prior anti-CSF1/CSF1R therapy. The study is being conducted in China (n=45), Europe (n=28), and the US and Canada (n=21).

       In the double-blind Part 1, 94 patients were randomized 2:1 to receive either 50 mg QD of pimicotinib (n=63) or placebo (n=31) for 24 weeks. The primary endpoint is objective response rate (ORR) at Week 25 as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by BIRC in the intent-to-treat (ITT) population. Secondary endpoints include tumor volume score, active range of motion, stiffness by Numeric Rating Scale (NRS), pain by Brief Pain Inventory (BPI), and physical function measured by PROMIS.

       After the double-blind Part 1, eligible patients may continue to the open-label Part 2 for up to 24 weeks of dosing. Patients who complete Part 2 may then enter the open-label extension phase (Part 3) for extended treatment and safety follow-up.

       Updated long-term follow-up results from the phase 1b study of pimicotinib in TGCT

       Abbisko also announced the updated results from the Phase 1 open-label, multicenter study evaluating the safety and efficacy of pimicotinib in patients with TGCT. The poster, titled, “Long-term efficacy and safety profile of Pimicotinib (ABSK021) in tenosynovial giant cell tumor: Phase 1b update,” will be presented at the Connective Tissue Oncology Society 2024 Annual Meeting in San Diego, United States on November 13-16, 2024.

       As of June 30, 2024, data from 42 patients who received the 50 mg dose of pimicotinib showed:

       - The best ORR was 85.0% by RECIST v1.1 per IRC. With a median treatment duration of 20.67 months (0.5, 30.1), 54.8% and 38.1% patients had an exposure of ≥ 18 months and ≥ 24 months, respectively. The median duration of response was not reached (NR) by Kaplan

       -Meier estimates, and 69.0% patients remained on treatment. Continuous and gradual improvement in tumor regression, pain and stiffness relief, and joint mobility were observed during long-term treatment.

       - The overall safety profile remains largely consistent, with no distinct adverse events emerging upon long-term follow-up.- No evidence of cholestatic hepatotoxicity was observed.

       關(guān)于和譽(yù)

       和譽(yù)醫(yī)藥(香港聯(lián)交所代碼:02256)是一家立足中國(guó),著眼全球的創(chuàng)新藥研發(fā)公司.公司的創(chuàng)始人和管理團(tuán)隊(duì)擁有多年頂尖跨國(guó)藥企的研發(fā)和管理經(jīng)驗(yàn),并參與了多個(gè)臨床及上市新藥的研發(fā).和譽(yù)醫(yī)藥專注于腫瘤新藥研發(fā),以小分子腫瘤精準(zhǔn)治療和小分子腫瘤免疫治療藥物為核心,著眼病患及醫(yī)藥市場(chǎng)的需求,秉承國(guó)際新藥開發(fā)的理念和標(biāo)準(zhǔn),致力于開發(fā)新穎及高潛力藥物靶點(diǎn)的潛在first-in-class或best-in-class創(chuàng)新藥物,用于改善中國(guó)及全球病人的生活質(zhì)量.

       自2016年成立以來(lái),和譽(yù)醫(yī)藥已擁有由16種候選藥物組成的產(chǎn)品管線,涵蓋腫瘤精準(zhǔn)治療領(lǐng)域以及腫瘤免疫治療領(lǐng)域.