This phase II trial compares the effect of immunotherapy with ipilimumab and nivolumab alone to their combination with cabozantinib in treating patients with soft tissue sarcoma that has spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply and may also prevent the growth of new blood vessels that tumors need to grow. By these actions it may help slow or stop the spread of cancer cells. Adding cabozantinib to the combination of ipilimumab and nivolumab may be better in stopping or slowing the growth of tumor compared to ipilimumab and nivolumab alone in patients with advanced soft tissue sarcoma.

开始日期2023-10-25

申办/合作机构

National Cancer Institute

NCT05944224 / Recruiting临床1/2期

A Randomized, Open-label, Phase Ib/IIa Clinical Study to Evaluate the Efficacy and Safety of SPH4336 Monotherapy or in Combination With Cadonilimab in Patients With Advanced Solid Tumors, Including Advanced Well Differentiated/Dedifferentiated Liposarcoma.

This is a randomized, Open-label, Phase Ib/IIa study to evaluate the efficacy and safety of SPH4336 monotherapy or in combination with Cadonilimab in the patients with selected advanced solid tumors.

开始日期2023-10-17

申办/合作机构

上海医药集团股份有限公司

ChiCTR2300075521 / Suspended临床1/2期IIT

Randomized, open, Phase Ib/IIa trial to evaluate the efficacy and safety of SPH4336 monotherapy or in combination with cadonilimab in the treatment of advanced solid tumors, including advanced highly differentiated/dedifferentiated liposarcoma

开始日期2023-09-10

申办/合作机构-

100 项与晚期脂肪肉瘤相关的临床结果

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100 项与晚期脂肪肉瘤相关的转化医学

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0 项与晚期脂肪肉瘤相关的专利（医药）

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项与晚期脂肪肉瘤相关的文献（医药）

2024-07-01·ESMO Open

Current unmet needs in locally advanced (unresectable) or metastatic dedifferentiated liposarcoma, the relevance of progression-free survival as clinical endpoint, and expectations for future clinical trial design: an international Delphi consensus report

Review

作者: Vincenzi, B ; Agulnik, M ; Italiano, A ; Blay, J Y ; Jones, R L ; Pink, D ; Wagner, M J ; Maki, R ; Valverde, C ; Stacchiotti, S ; Schöffski, P ; Chalmers, A

BACKGROUNDLocally advanced (unresectable) or metastatic dedifferentiated liposarcoma (DDLPS) is a common presentation of liposarcoma. Despite established diagnostic and treatment guidelines for DDLPS, critical clinical gaps remain driven by diagnostic challenges, symptom burden and the lack of targeted, safe and effective treatments. The objective of this study was to gather expert opinions from Europe and the United States on the management, unmet needs and expectations for clinical trial design as well as the value of progression-free survival (PFS) in this disease. Other aims included raising awareness and educate key stakeholders across healthcare systems.MATERIALS AND METHODSAn international panel of 12 sarcoma key opinion leaders (KOLs) was recruited. The study consisted of two rounds of surveys with pre-defined statements. Experts scored each statement on a 9-point Likert scale. Consensus agreement was defined as ≥75% of experts scoring a statement with ≥7. Revised statements were discussed in a consensus meeting.RESULTSConsensus was reached on 43 of 55 pre-defined statements across disease burden, treatment paradigm, unmet needs, value of PFS and its association with overall survival (OS), and cross-over trial design. Twelve statements were deprioritised or merged with other statements. There were no statements where experts disagreed.CONCLUSIONThis study constitutes the first international Delphi panel on DDLPS. It aimed to explore KOL perception of the disease burden and unmet need in DDLPS, the value of PFS, and its potential translation to OS benefit, as well as the relevance of a cross-over trial design for DDLPS therapies. Results indicate an alignment across Europe and the United States regarding DDLPS management, unmet needs, and expectations for clinical trials. Raising awareness of critical clinical gaps in relation to DDLPS can contribute to improving patient outcomes and supporting the development of innovative treatments.

2024-01-17·Clinical Cancer Research

SAR-096: Phase II Clinical Trial of Ribociclib in Combination with Everolimus in Advanced Dedifferentiated Liposarcoma (DDL) and Leiomyosarcoma (LMS)

Article

作者: Matloob, Sahar ; Pagan, Cheyenne ; George, Suzanne ; Choy, Edwin ; Veggeberg, Rosanna ; Barker, Emma ; Tetzlaff, Eric D. ; Rink, Lori ; Cai, Kathy Q. ; Zhou, Yan ; Merriam, Priscilla ; von Mehren, Margaret ; Movva, Sujana ; Flieder, Douglas B. ; Zumpano, Delia ; Handorf, Elizabeth A.

AbstractPurpose:Dedifferentiated liposarcoma (DDL) and leiomyosarcoma (LMS) are two common subtypes of soft-tissue sarcoma, a rare group of diseases for which new treatments are needed. Chemotherapy remains the standard option for advanced disease. Targeting cyclin-dependent kinase 4 and 6 (CDK4/6) in DDL and mTOR in LMS is of biologic interest. When combined, the CDK4 inhibitor ribociclib and the mTOR inhibitor everolimus have shown synergistic growth inhibition in multiple tumor models, suggesting that this combination could be beneficial in patients.Patients and Methods:This was a single arm, open label, multicenter phase II study of the combination of ribociclib and everolimus. Patients were enrolled into one of two cohorts: DDL or LMS with intact Rb. The primary endpoint was progression-free rate (PFR) at 16 weeks. Secondary endpoints included progression-free survival (PFS) and overall survival, safety and biomarker analyses.Results:In the DDL cohort, 33.3% [95% confidence interval (CI), 15.6%–55.3%] of patients were progression-free at 16 weeks. Median PFS in this cohort was 15.4 weeks (95% CI, 8–36 weeks) with 2 partial responses. In the LMS cohort the PFR at 16 weeks was 29.2% (95% CI, 12.6%–51.1%). Median PFS in this cohort was 15.7 weeks (95% CI, 7.7–NA). Most common toxicities included fatigue (66.7%), anorexia (43.8%), and hyperglycemia (43.8%). Concordance between Rb testing methodologies was poor.Conclusions:The combination of ribociclib and everolimus demonstrates activity in DDL with prolonged stable disease (≥16 weeks) meeting the primary endpoint. Notably partial responses were observed. The primary endpoint was not reached in the LMS cohort. The combination was well tolerated with expected side effects.

2024-01-01·In Vivo

Chemotherapy With Eribulin Following Potentially Curative Surgery in Patients With Localized Liposarcoma

Article

作者: Brodowicz, Thomas ; Steinbrecher, Oskar ; Popov, Petar ; Lamm, Wolfgang

BACKGROUND/AIMSoft tissue sarcomas are rare and heterogenous malignancies with high recurrence rates following resection and a poor prognosis in advanced stages. Eribulin is used in metastatic soft tissue sarcoma patients, who have failed first line chemotherapy and has been approved for patients with pretreated advanced liposarcoma (LPS) in the United States and Europe following the publication of data of a phase III trial. In addition, no data are available for eribulin as postoperative treatment after potentially curative surgery. We, thus, retrospectively evaluated efficacy and tolerability of adjuvant eribulin in patients with LPS not suitable for intensive chemotherapy in the routine clinical setting.PATIENTS AND METHODSIn this retrospective single center analysis, efficacy and safety of eribulin were retrospectively evaluated in five high risk LPS patients.RESULTSEribulin as treatment was administered to five patients with LPS following surgical resection. Median progression-free survival and overall survival were 12.3 months and 44.3 months, respectively. Toxicity was generally manageable, and grade 3+4 events were rare.CONCLUSIONPostoperative eribulin may be feasible in selected high risk LPS patients, who are not candidates for intensive chemotherapy regimens. Further prospective trials, however, are needed.

项与晚期脂肪肉瘤相关的新闻（医药）

2023-09-13

·药渡Daily

勃林格殷格翰MDM2-p53拮抗剂国内临床申请获受理

6月30日，CDE官网显示，勃林格殷格翰1类新药BI 907828片国内临床试验申请获受理。P53是一种肿瘤抑制基因，在大多数肿瘤中发现的p53突变会导致无法控制的细胞分裂。BI 907828是一种MDM2-p53拮抗剂，通过阻止MDM2-p53的相互作用，恢复p53的转录活性，从而介导肿瘤细胞凋亡。BI 907828对于胆道系统肿瘤、胰腺癌、肺或膀胱癌患者具有潜在疗效。初步研究显示，P53突变的肉瘤患者对BI 907828治疗有反应。目前勃林格殷格翰正在将该药与标准化疗药物结合进行研究。肉瘤是一种罕见的恶性肿瘤，发生于结缔组织，例如骨、软骨、肌肉、神经、血管以及脂肪和纤维组织，约占全球所有癌症的1%。87.3%的肉瘤发生于软组织中，如肌肉、神经、血管、脂肪和纤维组织，这些被称为软组织肉瘤（STS），其亚型众多，脂肪肉瘤（LPS）是最常见的亚型之一；另外12.7%的肉瘤为骨肉瘤，多起源于骨骼，也可起源于软骨。根据美国国家癌症研究所（NCI）的SEER数据库统计，肉瘤每年的总发病率不到5/10万。在今年的2023ASCO大会期间，勃林格殷格翰更新了BI 907828在TP53野生型MDM扩增的肉瘤中的Ib研究扩展队列的数据。试验共入组137例患者，中位治疗线数为2。6例发生毒性相关的治疗终止。20例（27.4%）为sAE，包括呕吐、肺栓塞、脓毒症和肠梗阻等。其中50例患者为DDLPS（高侵袭性的LPS亚型），均有MDM2扩增，其中42例可评价疗效，8例PR（19%），29例SD。DCR 88.1%，mPFS 8.1个月。2022年10月，勃林格殷格翰BI 907828片登记启动一项国际多中心（含中国）Ⅱ/Ⅲ期临床，评估BI 907828与多柔比星在晚期去分化脂肪肉瘤患者中作为一线治疗的有效性与安全性。今年1月5日，BI 907828用于一线治疗去分化脂肪肉瘤II/II期临床试验Brightline-1在四川大学华西医院成功入组首例DDLPS患者。●默沙东换道超车！Efinopegdutide与司美格鲁肽迎来NASH数据对比●渤健与以色列biotech合作探索“渐冻症”●KRAS抑制剂最新进展

ASCO会议临床结果临床1期临床2期临床申请

2023-08-23

·药智网

转出首个上市产品的部分商业化权利，德琪医药意欲何为？

近日，港股上市公司德琪医药发布公告称，与翰森制药达成独家合作协议，由翰森制药负责塞利尼索在中国大陆的商业化，德琪医药将获最高2亿元首付款及最高5.35亿元里程碑付款。据了解，塞利尼索是德琪医药首个上市商业化产品，从Karyopharm引进，拥有中国及其他亚太地区独家开发和商业化权利，在将塞利尼索推向上市两年后，将中国大陆的商业化权利再次转手，德琪医药意欲何为？01首个创新药产品，塞利尼索的成名之路在引入中国之前，塞利尼索归属Karyopharm公司。2019年7月，美国FDA批准塞利尼索用于治疗复发或难治性多发性骨髓瘤，当年在美销售收入为0.31亿美元；2020年在美适应症扩展，先后获FDA批准用于治疗复发或难治性弥漫性大b细胞淋巴瘤和至少一次既往治疗后多发性骨髓瘤患者，2020年销售收入实现145%的增长，最终在2022年成为Karyopharm收入过亿（美元）产品。数据来源：公开信息整理值得一提的是，塞利尼索在除中国及亚太地区外的“登陆”版图也越来越大，2021年以来已先后在以色列、英国、欧盟27个成员国以及冰岛、列支敦士登、挪威和北爱尔兰等获批上市，且在2022年获美国FDA和欧盟EC授予的骨髓纤维化(MF)孤儿药资格。德琪医药引入塞利尼索后，首个获批国家为韩国：2021年7月，塞利尼索联合地塞米松孤儿药上市申请获韩国MFDS批准，用于治疗已接受至少四种既往治疗复发或难治性多发性骨髓瘤成人患者，以及单药治疗既往接受过至少2线治疗复发难治性弥漫性大B细胞淋巴瘤(rrDLBCL)的成年患者。之后，塞利尼索在中国及亚太地区一路“绿灯”，又在新加坡、澳大利亚等地获批上市；2022年12月，德琪医药又向马来西亚、泰国提交NDA申请，获批在即。数据来源：德琪医药公告塞利尼索的上市，让德琪医药在2021年告别了无产品收入的时代，当年收入0.29亿元，2022年收入1.6亿元。随着塞利尼索在亚太地区获批范围以及适应症和给药治疗方式的持续拓展，塞利尼索将有更大市场空间。图片来源：德琪医药2022年报除了获批地域的扩大和适应症的扩展，塞利尼索也获得了国际认可，Karyopharm在2023年美国临床肿瘤学会（ASCO）年会和欧洲血液学会（EHA）年会上分别展示了塞利尼索的4项和3项研究数据。图片来源：Karyopharm官网另外，据德琪医药2022年报显示，塞利尼索的适应症有5项及11个给药方式的临床研究，且全部进入临床阶段，其中2项适应症的4个给药方式获批，另外有联合硼替佐米、地塞米松用于复发/难治性多发性骨髓瘤和单药治疗复发/难治性弥漫性大B细胞淋巴瘤的两项研究已进展至3期临床。图片来源：德琪医药2022年报一路走来，塞利尼索前途一片光明，为何在关键时候，德琪医药将首款上市产品的中国大陆商业化权利转出？02Biotech两大困境为何转出部分商业化权利，与Biotech两大困境有关。据德琪医药2021年报显示，塞利尼索的适应症研究并非只有5项，另外还包括非小细胞肺癌、骨髓纤维化、子宫内膜癌维持治疗、晚期脂肪肉瘤、新诊断及复发性脑胶质瘤，值得注意的是，就连最先获批的复发或难治性多发性骨髓瘤适应症，也有可能扩展至新诊断的多发性骨髓瘤，这些适应症都已推至临床阶段。图片来源：德琪医药2021年报以非小細胞肺癌为例，中国2019年有76.1万例，预计到2024年将达88.43万例，市场规模达964亿元，塞利尼索非小細胞肺癌临床研究在2021年都已进展至2期临床，而彼时国内尚无临床开发的SINE拟制剂可用于非小细胞肺癌治疗。时间就是金钱，“先到先得”的竞争铁律，让德琪医药在塞利尼索的发展选择上，采取了持续研发，联手商业化更为成熟的翰森制药，将已有适应症进行推广、销售。此外，据德琪医药2022年报显示，除塞利尼索外，德琪医药已进入临床阶段的管线产品还有8个，其中进展最快的是ATG-008，其联合特瑞普利单抗用于宫颈癌和晚期实体瘤已处于2期临床。ATG-008在2022年美国临床肿瘤学会（ASCO）年会上也展示了积极的临床数据，联合特瑞普利单抗治疗复发性或转移性宫颈癌的客观缓解率(ORR)为52.4%，PD-L1表达阳性受试者的ORR为77.8%。图片来源：德琪医药2022年报除了以上核心药物，还有2022年9月获美国FDA授予孤儿药资格的ATG-101，也等待着快速实现价值。除了集中力量研发创新药外，Biotech的销售费用过高，也是德琪医药转出商业化权利的另一重要原因。德琪医药2022年的销售及分销开支为3.55亿元，除去里程碑付款，有2.19亿元主要用于了产品市场推广，比2021年增长220%，主要是因塞利尼索的市场开发开支增加以及雇员成本增加，值得注意的是，2022年商业化雇员还比2021年减少了4名，此外塞利尼索上市以来的销售额合计为1.89亿元，而两年市场开发开支和雇员成本合计就有2.42亿元。图片来源：德琪医药2022年报而反观翰森制药，其商业化能力随着6款创新药在中国获批上市得到大幅提高。2022年，翰森制药创新药销售收入约为50.6亿元，占比由2021年的42.3%上升至53.4%，近五年来，除2018年销售及分销开支为收入的42%外，自2019年起均未超过40%，且较为稳定，没有过大起伏，2022年为38%。图片来源：翰森制药2022年报翰森制药商业化的接力，让德琪医药无市场商业化后顾之忧，安心研发创新药，也不排除后续将更多的地域商业化权利再转交给翰森制药或其他药企。03小结研发不易，商业化更不易，然而造药也好，卖药也罢，除了金钱的收益，患者的健康也是药企孜孜不倦的追求，德琪医药将首款产品交由“他人”代卖，除了考虑降低销售成本外，更多的是考虑“好钢用在刀刃上”，将有限的资源用在药物的潜力开发上，只有走得更好，才能走的更远。声明：本内容为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 八角转载开白 | 马老师 18996384680（同微信）商务合作 | 王存星 19922864877（同微信）阅读原文，是昨天最受欢迎的文章哦

孤儿药引进/卖出上市批准ASCO会议医药出海

2023-03-29

·医药观澜

速递！上海医药CDK4/6抑制剂获FDA孤儿药资格

▎药明康德内容团队报道3月29日，上海医药发布公告称，其自主研发的SPH4336用于脂肪肉瘤适应症获得美国FDA授予孤儿药资格。公开资料显示，这是一款CDK4/6抑制剂，正在中国开展针对晚期实体瘤的1期临床试验，以及在美国开展针对局部晚期或转移性脂肪肉瘤的2期临床试验。脂肪肉瘤（LPS）是软组织肉瘤中常见的组织学类型，约占软组织肉瘤的20%。手术切除是当前脂肪肉瘤治疗的主要手段，可用的靶向治疗及免疫治疗的药物及疗效均非常有限。晚期脂肪肉瘤患者往往预后差、复发率高。因此，全面了解脂肪肉瘤的病理特点，探索并开发新型、有效的针对脂肪肉瘤的治疗方案，是亟待解决的临床问题。SPH4336是一种新型高选择性口服抑制剂，具有广谱的抗肿瘤作用。该产品对CDK4/6靶点具有较高的选择性，同时具有广谱抗Rb阳性肿瘤活性。在临床病人来源的脂肪肉瘤PDX的裸小鼠皮下移植瘤模型上，SPH4336显示出较好的抗肿瘤作用。在中国开展的针对晚期实体瘤的1期临床试验数据显示，该产品具有良好的药效、较高的安全性和优良的药代动力学性质，即将进入中国1b/2a期脂肪肉瘤临床研发。今年3月，上海医药与康方生物旗下康方药业签订新药联用开发合作协议，共同推进CDK4/6抑制剂SPH4336片联合PD-1/CTLA-4双特异性抗体新药开坦尼（卡度尼利单抗注射液），针对高分化脂肪肉瘤（WDLS）/去分化脂肪肉瘤（DDLS）等肿瘤适应症。上海医药在公告中表示，本次SPH4336获得FDA孤儿药资格，能够加快推进临床试验及上市注册的进度。参考资料：[1]上海医药集团股份有限公司关于SPH4336获得美国FDA孤儿药资格认定的公告. Retrieved Mar 29 2023 from http://www.cninfo.com.cn/new/disclosure/detail?stockCode=601607&announcementId=1216242771&orgId=gssh0600849&announcementTime=2023-03-29[2]上海医药集团股份有限公司关于与康方药业签订新药联用开发合作协议的公告 Retrieved Mar 8， 2023, from http://www.cninfo.com.cn/new/disclosure/detail?stockCode=601607&announcementId=1216063930&orgId=gssh0600849&announcementTime=2023-03-08本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈。转发授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

孤儿药免疫疗法临床2期临床1期