Phase 1b/2 Trial Using Neoadjuvant Lurbinectedin With Concurrent Preoperative Radiation in Patients With Locally Advanced Soft Tissue Sarcomas of Extremity, Trunk, and Retroperitoneum

This is a multi-center, multi-arm open-label phase Ib/II clinical study assessing the efficacy of concurrent lurbinectedin in combination with radiotherapy in patients with locally advanced, resectable, high-grade sarcomas.

开始日期2024-10-31

申办/合作机构

The University of California, San Francisco

[+1]

NCT06496048

/ Recruiting临床3期

A Phase III, Multicenter, Randomized, Open-label Study of Lurbinectedin As Monotherapy or in Combination with Irinotecan Versus Topotecan in Patients with Relapsed Small-cell Lung Cancer (SCLC)

Multicenter, open-label, randomized, controlled phase III clinical trial to evaluate and compare the activity and safety of two experimental arms consisting of Lurbinectedin monotherapy or Lurbinectedin + Irinotecan combined therapy versus Topotecan comparator in Small-cell Lung Cancer (SCLC) patients who failed one prior platinum-containing line.

开始日期2024-09-14

申办/合作机构

綠葉製藥集團有限公司

100 项与芦比替定相关的临床结果

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100 项与芦比替定相关的转化医学

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100 项与芦比替定相关的专利（医药）

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216

项与芦比替定相关的文献（医药）

2025-07-01·LUNG CANCER

Lurbinectedin for extensive stage − small cell lung cancer (ES-SCLC): real world response patterns and survival outcomes

Article

作者: Basel, Afifi ; Roisman, Laila C ; Sorotsky, Hadas Gantz ; Peled, Nir ; Krayim, Belal ; Rotem, Ofer ; Kian, Waleed ; Mann, Shir ; Hanovich, Ekaterina ; Urban, Damian ; Asna, Noam ; Kornev, Gleb ; Gillis, Roni ; Bar, Jair ; Shalata, Walid ; Moskovitz, Mor ; Marie, Ranin

BACKGROUND:

Small cell lung cancer (SCLC) remains a therapeutic challenge with limited treatment options and poor survival outcomes. Lurbinectedin has been approved for the post-platinum setting, but there is a lack of real-world evidence and information related to its optimal sequencing and effectiveness across different lines of therapy. This study aimed to analyze line-dependent outcomes and response patterns of lurbinectedin in SCLC patients.

METHODS:

In this retrospective multi-center study analysis, we enrolled SCLC patients treated with lurbinectedin between January 2020 and December 2024. Patient demographics, treatment histories, and outcomes were collected from electronic medical records. Response assessment was performed using RECIST v1.1 criteria. Overall survival, progression-free survival, and treatment duration were analyzed using Kaplan-Meier methodology, with specific attention to outcomes across different lines of therapy.

RESULTS:

A total of 64 patients were enrolled, with 59 evaluable for analysis (36 males [56.3 %], median age 65 years [range 37-81]). Lurbinectedin was given as second-line therapy in 39 patients (66.1 %) and as third-line or beyond in 20 patients (33.9 %). The overall response rate (ORR) was 37.3 % (n = 22), including 1 complete response (1.7 %) and 21 partial responses (35.6 %). By line of therapy, the ORR was 38.5 % (n = 15) in second-line and 35.0 % (n = 7) in third-line or later. The median overall survival (mOS) for all evaluable patients was 7.7 months, and the median duration of treatment (mDoT) was 4.3 months. At data cutoff, 13 patients (22 %) were alive and censored in the OS analysis, with a median follow-up of 8.5 months among survivors. Prior immune checkpoint inhibitor (IO) exposure was documented in 71.9 % of patients (n = 46); although those with prior IO had numerically longer mOS (8.8 vs. 6.0 months, p = 0.06) and mDoT (4.6 vs. 2.3 months, p = 0.14), neither difference reached statistical significance. This survival analysis included 43 patients in the prior-IO group (3 patients with prior IO were excluded due to incomplete follow-up) and 16 patients in the no-IO group. The presence of baseline brain metastases (47 %) did not preclude clinical benefit. Treatment was generally well tolerated: the most common hematologic toxicities observed were anemia (44.1 %), thrombocytopenia (37.3 %), and neutropenia (15.3 %), predominantly grade 1-2, and no grade 4 adverse events were observed.

CONCLUSIONS:

Lurbinectedin demonstrated meaningful clinical activity in second-line therapy for SCLC, while also showing durable responses in heavily pretreated cases. These findings support the consideration of lurbinectedin also beyond second-line therapy in selected SCLC patients, though larger prospective studies are needed to validate these response patterns.

2025-06-04·MOLECULAR CANCER THERAPEUTICS

Unveiling the Mechanism of Lurbinectedin’s Action and Its Potential in Combination Therapies in Small Cell Lung Cancer

Review

作者: Cuevas, Carmen ; Avilés, Pablo ; Martinez Diez, Marta ; Calles, Antonio ; Egly, Jean-Marc ; Calvo, Emiliano ; Guillén, María José ; Gupta, Aparna ; Costanzo, Federico ; Santamaría Nuñez, Gema

Abstract:

Lurbinectedin is a selective inhibitor of oncogenic transcription approved for the treatment of adult patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy. Preclinical data provide evidence for lurbinectedin exerting its actions in a unique manner that involves oncogenic transcription inhibition, DNA damage, reshaping of the tumor microenvironment, and inducing anticancer immunity. Understanding the mechanism of action has facilitated the rational combination of lurbinectedin and anticancer therapies with complementary modes of action, in order to obtain synergistic effects that could potentially lead to improved efficacy. This review evaluates the mechanism of action for lurbinectedin and provides an overview of the therapeutic landscape with regards to lurbinectedin combination therapies for the treatment of small cell lung cancer based on data from preclinical and clinical studies.

2025-06-01·LANCET

Efficacy and safety of first-line maintenance therapy with lurbinectedin plus atezolizumab in extensive-stage small-cell lung cancer (IMforte): a randomised, multicentre, open-label, phase 3 trial

Article

作者: Iannone, Robert ; Czyżewicz, Grzegorz ; Majem, Margarita ; Chakrabarti, Debasis ; Lin, Ya-Chen ; Graupner, Vilma ; Csőszi, Tibor ; Grohé, Christian ; Caro, Reyes Bernabé ; Peters, Solange ; Baka, Sofia ; Reck, Martin ; Borghaei, Hossein ; Şendur, Mehmet Ali Nahit ; Liu, Stephen V ; Cai, George ; Lee, Ki Hyeong ; Paz-Ares, Luis ; Bhatt, Kamalnayan ; Kemal, Yasemin ; Ballinger, Marcus ; Cuchelkar, Vaikunth ; Stencel, Katarzyna ; Yang, Tsung-Ying ; Califano, Raffaele ; Ahn, Jin Seok ; Johnson, Melissa L ; Karadurmuş, Nuri ; Herbst, Roy S

BACKGROUND:

Despite improved efficacy with first-line immune checkpoint inhibitors plus platinum-based chemotherapy for extensive-stage small-cell lung cancer (ES-SCLC), survival remains poor. In this study, we aimed to compare lurbinectedin plus atezolizumab and atezolizumab alone as maintenance therapies in patients with ES-SCLC without progression after induction therapy with atezolizumab, carboplatin, and etoposide.

METHODS:

IMforte was a randomised, open-label, phase 3 trial done at 96 hospitals and medical centres in 13 countries (Belgium, Germany, Greece, Hungary, Italy, Mexico, Poland, South Korea, Spain, Taiwan, Türkiye, the UK, and the USA). Eligible patients were aged 18 years or older with treatment-naive ES-SCLC. Patients received four 21-day cycles of induction treatment (atezolizumab, carboplatin, and etoposide). After completing induction treatment, eligible patients without disease progression were randomly assigned (1:1) using permuted blocks (Interactive Voice/Web Response System) to receive maintenance treatment intravenously every 3 weeks with lurbinectedin (3·2 mg/m²; with granulocyte colony-stimulating factor prophylaxis) plus atezolizumab (1200 mg) or atezolizumab (1200 mg). The two primary endpoints were independent review facility-assessed (IRF) progression-free survival and overall survival, measured from randomisation into the maintenance phase. Efficacy endpoints were assessed in the full analysis set, which included all patients who were randomly assigned to maintenance phase treatment, regardless of whether they received their assigned study treatment. Safety was assessed in all patients who received at least one dose of lurbinectedin or atezolizumab, and was analysed according to the treatment received. This study is registered with ClinicalTrials.gov, NCT05091567, and is closed for recruitment.

FINDINGS:

Between Nov 17, 2021, and Jan 11, 2024, 895 patients were screened for enrolment, of whom 660 (74%) were enrolled into the induction phase. Between May 24, 2022, and April 30, 2024, 483 (73%) of 660 patients entered the maintenance phase and were randomly assigned to lurbinectedin plus atezolizumab (n=242) or atezolizumab (n=241). At the data cutoff (July 29, 2024), IRF progression-free survival was longer in the lurbinectedin plus atezolizumab group than the atezolizumab group (stratified hazard ratio [HR] 0·54 [95% CI 0·43-0·67]; p<0·0001), as was overall survival (stratified HR 0·73 [0·57-0·95]; p=0·017). 92 (38%) of 242 patients in the lurbinectedin plus atezolizumab group and 53 (22%) of 240 patients in the atezolizumab group had grade 3-4 adverse events. The most common grade 3-4 events in the lurbinectedin plus atezolizumab group were anaemia (20 [8%] of 242 patients), decreased neutrophil count (18 [7%] patients), and decreased platelet count (18 [7%] patients) and the most common events in the atezolizumab group were hyponatremia (five [2%] of 240 patients), dyspnoea (four [2%] patients), and pneumonia (four [2%] patients). Grade 5 adverse events occurred in 12 (5%) of 242 patients in the lurbinectedin plus atezolizumab group and six (3%) of 240 patients in the atezolizumab group. The incidence of myelosuppressive toxicities (eg, neutropenia and leukopenia) was higher in the lurbinectedin plus atezolizumab group than the atezolizumab group.

INTERPRETATION:

IRF progression-free survival and overall survival were longer in the lurbinectedin plus atezolizumab group than the atezolizumab group for patients with ES-SCLC, albeit with a higher incidence of adverse events. Lurbinectedin plus atezolizumab represents a novel therapeutic option for first-line maintenance treatment in this setting.

FUNDING:

F Hoffmann-La Roche and Jazz Pharmaceuticals.

277

项与芦比替定相关的新闻（医药）

2025-06-20

·癌度

癌症治疗疫苗时代践行者，PD-L1抑制剂联合个体化肿瘤新抗原疫苗 PGV001治疗尿路上皮癌！

临床试验入组病友交流群（点击）PD-1/PD-L1等免疫检查点抑制剂（ICI）已经改变了多种肿瘤的治疗方法，但是很多患者并不能从免疫检查点抑制剂里获益，以尿路上皮癌患者来说，在高风险肌层浸润性尿路上皮癌中，即使进行了根治性手术和辅助治疗使用了免疫检查点抑制剂，仍然有大概50%的患者会发生转移和复发。转移性尿路上皮癌中，接受免疫检查点抑制剂治疗的患者只有20%到30%可获得持续缓解。为此，大家将目光转向了联合治疗，以提升治疗的应答率。经过了一系列的研究，科学家认为通过治疗性疫苗联合免疫检查点抑制剂来诱导抗肿瘤免疫会比较给力，癌症疫苗针对的是癌细胞特别的抗原，特别是根据癌细胞的基因突变系列而导致的新型肿瘤抗原（新抗原）。下面就是一项最近发布在国际学术期刊的研究，通过新抗原个体化基因组疫苗PGVV001与PD-L1抑制剂阿替利珠单抗联合治疗尿路上皮癌的研究。癌度为大家整理这篇文献的内容，从此我们可以看出癌症治疗的新时代已经到来！本文参考文献刊例示意图1、泰胜奇与癌症治疗疫苗PGV001的首次联合人体临床试验这个研究使用了Open-vax计算机流程进行新抗原预测和筛选，2018年12月至2020年8月期间，12名参与者进入了疫苗的开发阶段，随后10名参与者开始进入治疗阶段。其中4名参与者进入辅助治疗阶段，6名参与者则是进入了转移性治疗阶段（其中3名患者肝转移）。数据统计时1名患者因为肿瘤样本不足进行基因测序而未进行疫苗开发，1名参与者的转移性疾病进展迅速而不符合研究分析标准。泰胜奇联合癌症疫苗PGV001研究的治疗结果上面的图示表示肿瘤病灶相比开始治疗时的变化，如果病灶缩小超过30%则为部分缓解（绿色曲线），偏下的图示表示一个患者在治疗前后多发的肝转移病灶的影像学检查，能看到在2个治疗周期后病灶几乎缩小不见了。这个研究的中位随访时间是39个月，4名接受辅助治疗的受试者中有3名没有出现复发，5名晚期接受转移性治疗且病灶可测量的患者有2名获得了客观缓解（肿瘤病灶缩小30%以上），所有的受试者均在治疗过程中出现了肿瘤新抗原特异性T细胞反应。因此，肿瘤新抗原疫苗联合免疫检查点抑制剂阿替利珠单抗是可行且安全的，达到了研究的终点。2、治疗尿路上皮癌只是一个开始从上面的这个研究的治疗机制看，PGV001癌症治疗疫苗联合阿替利珠单抗可以治疗多种实体肿瘤，只是这个联合用药刚刚开始在尿路上皮癌启动了而已。还需要注意有患者因为肿瘤样本不足基因检测而不能制备癌症治疗疫苗，这也是为何有时候我们癌度也建议患者可以适度做个一个比较大的基因检测套餐，如果说之前和现在还停留在找靶向药，那么未来的时代则是根据肿瘤的基因突变信息设计癌症治疗疫苗，而肿瘤组织样本如果超过1年或2年则不能进行相应的基因检测了，后面使用这些基因突变信息做癌症治疗疫苗则没了替代办法。需要说明的是癌症治疗疫苗PGV001联合阿替利珠单抗的研究是在国外开展的，国内暂时没有同类别的临床试验，但是应该很快就会出现类似的临床试验，而且癌症治疗疫苗联合免疫检查点抑制剂将不仅仅招募尿路上皮癌，包括肺癌、胰腺癌、乳腺癌等等都是可能的。欢迎大家联系癌度，为大家解读基因检测报告、加入癌度临床试验病友交流群，我们一起期待癌症治疗疫苗时代的到来！参考文献：Mansi Saxena, et al., Atezolizumab plus personalized neoantigen vaccination in urothelial cancer: a phase 1 trial, Nature Cancer (2025). 往期推荐肺癌脑膜转移的治疗策略PK，EGFR靶向药联合抗血管生成靶向药胜出，肝转移和大于3个转移灶是不利因素！靶向药失败后，还有希望吗？——新一代“抗体偶联药”药物，为EGFR突变肺癌带来转机！ASCO2025报道：降低小细胞肺癌复发、进展风险，一线治疗后免疫治疗加上芦比替定就可以了！“原本不能手术的肺癌，她竟做了根治切除术”——一种新组合疗法带来的逆转奇迹！

2025-06-19

·癌度

肺癌脑膜转移的治疗策略PK，EGFR靶向药联合抗血管生成靶向药胜出，肝转移和大于3个转移灶是不利因素！

临床试验入组病友交流群（点击）软脑膜转移是晚期肿瘤的一种严重并发症，主要的发生原因是肿瘤细胞通过各种途径转移到软脑膜、蛛网膜、蛛网膜下腔和其他脑脊液（CSF）腔引起的。非小细胞肺癌患者比较容易出现脑膜转移，发生脑膜转移给患者的生活质量和总生存时间带来了严重的负面影响。对于EGFR基因阳性突发的晚期非小细胞肺癌，脑膜转移的发生率呈现上升趋势，发生的概率高达9%至16%，而整体的晚期非小细胞肺癌发生脑膜转移的概率仅为3%到5%。30%的晚期非小细胞肺癌使用EGFR靶向药治疗后会发生中枢神经系统转移，目前治疗办法包括：化疗、放疗、鞘内治疗、靶向药治疗和免疫治疗。但是对于脑膜转移的肺癌患者来说，目前没有标准治疗方法。抗血管生成靶向药如贝伐单抗等可以增强EGFR靶向药的治疗效果，即便是驱动基因阴性的肺癌患者，使用贝伐单抗联合铂类化疗也是会更好一些。今天癌度给大家编译的一瓶国际文献报道，探讨现实生活中，非小细胞肺癌患者进展至脑膜转移之前和转移之后，使用驱动基因EGFR靶向药联合抗血管生成靶向药的疗效，希望本文对大家有所帮助。本文参考文献刊例示意图1、两种类型靶向药对肺癌脑膜转移的疗效对于口服的靶向药分为两类，一类是针对肿瘤的驱动基因的靶向药，比如EGFR或ALK基因突变才使用的靶向药，这些靶向药主要是抑制肿瘤的驱动基因，也是往往能达到最佳治疗效果的靶向药，使用这些药物需要先进行基因检测明确患者携带相应的基因突变。还有一类靶向药则是抗血管生成机制，典型的如贝伐单抗、安罗替尼、仑伐替尼、阿帕替尼、索拉非尼等等，这些药物通过阻断肿瘤血管生成来达到抑制肿瘤病灶生长的目的，这些药物的使用不需要进行基因检测，任何的肿瘤患者其实都是可以使用，但是通过抑制肿瘤血管生长往往不是很有效果，因为肿瘤有多种机制来产生耐药性。今天癌度给大家分享的这个研究纳入了晚期非小细胞肺癌患者，这些患者有的存在EGFR基因突变，有的则是EGFR基因突变阴性，这些患者在发生脑膜转移之前和之后接受了不同的治疗，研究汇总了患者的生存期数据。主要研究从确诊为非小细胞肺癌到发生脑膜转移的时间（无脑膜转移生存期，mLFS），以及总生存期。两大类靶向药治疗对肺癌脑膜转移的疗效77名晚期非小细胞肺癌患者接受了EGFR靶向药联合抗血管生成靶向药治疗，无脑膜转移的生存时间是19个月，中位总生存时间是21.9个月。而单独使用EGFR靶向药的肺癌患者无脑膜转移生存期是14个月。如果患者的转移病灶超过3个部位，则往往无脑膜转移的生存期就比较短，肝转移是患者总生存时间比较差的独立预测饮食。2、关于脑膜转移，上述研究结论上面的这个研究总体的结论是：EGFR靶向药联合抗血管生成靶向药，可能是延长患者无脑膜转移生存期和总生存期的办法，也就是说确诊后将驱动基因的靶向药和抗血管生成靶向药组合，能延缓脑膜转移的发生。但是如果转移病灶超过了3个、或有肝转移则往往是预后不好。这个可能也比较好理解，因为出现了更多的转移灶，往往意味着患者循环肿瘤细胞很多，容易发生脑膜转移。关于脑膜转移的治疗、肺癌靶向药和临床试验免费用药信息，欢迎大家关注癌度，加入癌度病友群咨询。参考文献：Xiao-dan Zhu, et al., Combination of antiangiogenic and systemic therapy in advanced non-small cell lung cancer: before and after progression to leptomeningeal metastasis, Scientific Reports volume 15, Article number: 11901 (2025). 往期推荐靶向药失败后，还有希望吗？——新一代“抗体偶联药”药物，为EGFR突变肺癌带来转机！ASCO2025报道：降低小细胞肺癌复发、进展风险，一线治疗后免疫治疗加上芦比替定就可以了！“原本不能手术的肺癌，她竟做了根治切除术”——一种新组合疗法带来的逆转奇迹！《音乐故事》第二首——“以死相托”的他阐释了什么是生命最后的温柔！

免疫疗法临床研究上市后研究临床终止

2025-06-18

·ioncology

ASCO 2025丨研究者解读：同步放化疗后阿替利珠单抗巩固治疗是否可延长局限期小细胞肺癌患者生存

点上方蓝字“ioncology”关注我们，然后点右上角“…”菜单，选择“设为星标”ASCO 2025 微专辑扫描二维码可查看更多内容局限期小细胞肺癌（LS-SCLC）是一种以预后不良为主要特点的高度侵袭性肿瘤。同步放化疗（CCRT）仍然是其标准治疗手段，其高复发率和较差的长期生存率凸显了对新型治疗方法的迫切需求。近年来，以免疫检查点抑制剂（ICIs）为代表的免疫疗法的引入，为LS-SCLC的治疗开辟了新的途径。在2025年美国临床肿瘤学年会（2025 ASCO）上，来自挪威圣奥拉夫医院的Bjørn Henning Grønberg教授团队主持开展的一项探究同步放化疗（CRT）后阿替利珠单抗是否可延长局限期小细胞肺癌（LS-SCLC）患者生存的随机II期临床研究成果入选LBA。《肿瘤瞭望》特邀Bjorn Henning Gronberg教授现场解读该项研究成果、分享LS-SCLC领域免疫治疗临床实践现状及未来展望。特此整理，以飨读者。专家简介Bjørn Henning Grønberg 教授挪威特隆赫姆大学医院圣奥拉夫医院肿瘤科医生挪威科技大学临床与分子医学系教授挪威危及生命疾病患者医学专家委员会成员挪威肺癌研究小组董事会成员国际肺癌研究协会（IASCL）、美国临床肿瘤学会（ASCO）、欧洲肿瘤内科学会（ESMO）成员研究介绍摘要号：LBA8005英文标题：Randomized phase II trial investigating whether atezolizumab after chemoradiotherapy (CRT) prolongs survival in limited stage (LS) small cell lung cancer (SCLC).探究放化疗（CRT）后阿替利珠单抗是否延长局限期小细胞肺癌（LS-SCLC）患者生存的随机 II 期试验研究背景大多数局限期小细胞肺癌（LS-SCLC）患者在接受潜在治愈性同步放化疗（CRT）后会复发，因此需要更优的治疗方案。免疫治疗可延长广泛期小细胞肺癌（ES-SCLC）患者的生存，且在非小细胞肺癌（NSCLC）患者接受CRT后应用亦有获益。基于此，我们开展了本项CRT后应用阿替利珠单抗（atezo）是否能延长LS-SCLC患者的生存期的临床研究。研究方法纳入体力状态评分（PS）0-2 分、接受铂类/依托泊苷化疗联合每日两次胸部放疗（TRT，45 Gy/30次或60 Gy/40次）后未进展（PD）的患者，按1:1比例随机分配至观察组或阿替利珠单抗组（1200 mg，每3周1次，持续1年，直至疾病进展或出现不可耐受毒性）。阿替利珠单抗在CRT后3-7周开始给药。随机化按体力状态（PS 0-1 vs. 2）、CRT反应（疾病稳定 [SD] vs. 完全/部分缓解 [CR/PR]）和TRT剂量（45 Gy vs. 60 Gy）进行分层。CRT 缓解者可接受25-30 Gy预防性脑照射（PCI），且允许在阿替利珠单抗治疗开始后进行PCI。主要终点为总生存期（OS），次要终点包括缓解率（ORR）、无进展生存期（PFS）和毒性。为了显示2年总生存率从53%改善至66%，在单侧α水平为0.1和β为0.2的情况下，每组需要75名可评估患者。研究结果患者基线：2018年7月至2022年4月期间，欧洲37家医院共纳入216例患者，其中170例（78.7%）完成随机分组（阿替利珠单抗组85例，观察组85例）。中位年龄66岁，46%为女性，92%的患者PS 0-1 分，82%为III期疾病。阿替利珠单抗组与观察组的CRT客观缓解率（ORR）相近（分别为 95% 和 94%），两组各67% 的患者接受了PCI。阿替利珠单抗的中位治疗周期数为8次（范围 0-18 次），2%的患者未接受治疗，35.2%完成1年疗程。停药原因包括疾病进展（n=18）、肺炎（n=8）、内分泌病变（n=3）、神经毒性（n=2）、肌炎（n=2）、其他毒性（n=9）、患者意愿（n=5）、其他疾病导致死亡（n=2）及其他原因（n=5）。因毒性停药的中位时间为2.8个月（0.1-12.1个月）。安全性评估：随机分组后（即CRT治疗后），阿替利珠单抗组34%报告3-4级毒性事件，对照组为20%。治疗相关死亡3例（神经毒性、肺炎和肺部感染），均发生在阿替利珠单抗组。有效性评估：中位随访45.1个月（95% CI 40.7-47.3）后，从随机分组开始计算的中位OS在阿替利珠单抗组为43.3个月（95% CI 25.1-51.2），观察组为 38.8 个月（95% CI 25.8 - 未达到）（HR 1.14，95% CI 0.76-1.72；p=0.5）。中位PFS在阿替利珠单抗组为21.1个月（95% CI 9.5-43.4），观察组为15.9个月（95% CI 10.6-23.2）（HR 0.88，95% CI 0.60-1.28，p=0.5）。研究结论阿替利珠单抗巩固治疗在大多数接受铂类/依托泊苷化疗及每日两次胸部放疗（BID TRT）后未进展的局限期小细胞肺癌（LS- SCLC）患者中具有耐受性，但未改善LS-SCLC患者的无进展生存期或总生存期。肿瘤瞭望首先，请您分享下目前局限期小细胞肺癌临床实践现状，现有治疗方案在哪些方面亟待优化？Bjørn Henning Grønberg教授众所周知，局限期小细胞肺癌（LS-SCLC）的治疗主要采用化疗联合放疗手段，标准治疗方案为铂类（如顺铂或卡铂）联合依托泊苷，并同步进行胸部放疗（TRT）。TRT方案包括每日两次（45 Gy/30次）或每日一次（66-70 Gy/33-35次），其中，我们发现TRT方案的选择对疗效的影响存在相当大的差异，每日一次的剂量递增方案并不能改善生存，有两项重要的中国临床研究为高剂量、加速、超分割的双日胸部放射治疗方案的临床实践提供了有力的数据支撑，结果显示与标准剂量45 Gy的同步化疗相比，采用高剂量、加速、超分割、每日两次的胸部放射治疗（同步化疗），剂量达到54Gy时可显著提高LS-SCLC中国患者的总生存率、无进展生存率和局部无进展生存率，同时毒性反应相似。这可能需要进一步验证，但就个人而言，我认为这是改善CRT的最佳方法，毕竟CRT目前仍是LS-SCLC治疗的支柱。此外，免疫检查点抑制剂（ICIs）在广泛期小细胞肺癌（ES-SCLC）中已取得突破，但其在LS-SCLC中的应用仍较为有限。但我想这只是时间问题，相关循证医学证据已在不断积累，在我的国家挪威，该疗法已得到应用并纳入医保。Prof. Bjørn Henning Grønberg: I think everybody agrees that platinum/etoposide is the standard chemotherapy regimen. There's been some discussion about choice of platinum. This platinum has been preferred, but I think now we have more data suggesting that carboplatin is equally effective. I think everybody also agrees that thoracic radiotherapy（TRT）should be administered concurrently with the chemotherapy, but we see that quite a large variation in the choice of TRT schedule, I think we now know that dose escalation with once daily regimens is not improving survival that are quite solid data on those escalation by acceleration. There are two Chinese trials showing that high dose twice daily radiotherapy of 60 grade was superior to 45 grade. Probably needs a confirmation. But personally, I believe this is the best approach for improving CRT which is still the backbone in the treatment of a limited state small cell lung cancer. Additionally，ICIs have achieved breakthroughs in extensive-stage small cell lung cancer （ES-SCLC）, but their application in limited-stage disease remains limited.I guess it's just a matter of time. I think the evidence is there. It's already implemented and reimbursed in my country in Norway. I guess it's just a matter of having all the approvals and there's discussion about reimbursement. 肿瘤瞭望伴随着ICIs在ES-SCLC中的取得进展，LS-SCLC的免疫治疗也成为研究的热点。本届ASCO，您的团队主持开展的探究放化疗（CRT）后阿替利珠单抗巩固治疗在LS-SCLC临床疗效探索研究入选LBA，请您解读下该项研究主要研究成果？Bjørn Henning Grønberg教授这是一项在欧洲开展的临床研究，共纳入了来自欧洲六个国家的37家医院的260例患者，均接受了铂类联合依托泊苷的化疗方案同步每日两次45~60 Gy TRT 方案，患者按 1:1 比例随机分配至阿替利珠单抗组或对照组，治疗时间为1年。我们发现阿替利珠单抗组的中位治疗周期为8次。尽管试验组不良事件发生率更高，但未发现新的安全信号，35.2%的患者完成了1年治疗。然而，我们未发现主要终点总生存期（OS）及无进展生存期（PFS）的获益，其中，在亚组分析中可见女性患者生存获益存在差异，随机分配至观察组的患者生存期比预期长得多，这或许能解释为何生存曲线与我们预期的有所不同。此外，我们还发现接受卡铂治疗的患者似乎更容易从阿替利珠单抗中获益，这在阿替利珠单抗组的亚组分析中也有体现，由此提示，本研究中或许存在一些我们未知的组间不均衡因素，或为导致本研究取得阴性结果的原因。Prof. Bjørn Henning Grønberg: This was a European trial. We enrolled 260 patients at 37 hospitals in six countries of Europe. Patients who completed platinum/etoposide chemotherapy and twice daily thoracic radiotherapy（TRT）of 45 to 60 grade were randomized 1:1 to receive either 1 year atezolizumab or observation. We saw that the median treatment period in the atezolizumab was eight infusions. There were some more adverse events in the experimental arm, but we didn't see any new safety signals, and 35 % of the patients completed 1 year of treatment. However, we did not find the benefit in terms of overall survival, which was the primer endpoint or PFS, but looking into subgroups, we saw that there were some differences among women, their survival among the patients randomized to the observation arm was much longer than expected. And that can maybe explain why the survival curves looks a little bit different than what we expected. Furthermore, we also saw that the patients will receive carboplatin. Those patients appeared to benefit from atezolizumab. This is something that was also shown in subgroup analysis of atezo group. So maybe there are some imbalances that we do not know about. That can maybe explain why this trial was negative.肿瘤瞭望基于现阶段研究进展，请您分享下未来免疫治疗在LS-SCLC领域有何探索方向？Bjørn Henning Grønberg教授首先，我认为我们需要明确如何识别那些在接受前期治疗后病情已得到控制的患者，因为这类患者显然无需再进行免疫治疗。而在其他患者中，我认为我们需要明确可真正能从免疫治疗中获益的人群，尽管现有研究表明免疫治疗可使LS-SCLC患者获益，但可能部分患者获益甚微，甚至毫无获益，另有一些患者甚至在长期生存方面实现获益，因此我们需要从正在进行的研究中获取更长时间的随访数据。此外，我们仍需在预测性生物标志物层面不断挖掘探索。Prof. Bjørn Henning Grønberg: First of all，I think we need to know how we can identify the patient who secured after accumulated therapy, because those patients obviously do not need immunotherapy. And then among the other patients, I think we need to understand how we can identify the patients who truly benefit from the immunotherapy. There is an effect in the overall population, but probably there's some patients who do not benefit much and maybe not at all. And then there are some patients who truly benefit in terms of long term survival. We need longer follow up data from ongoing trials. I think we also need data from other trials that haven't been presented yet. And then, of course we do need predictive biomarkers for the treatment of the small cell lung cancer, in general. 肿瘤瞭望请您为我们分享下本届ASCO，您所关注的肺癌领域热点研究及话题有哪些？Bjørn Henning Grønberg教授首先，SCLC领域，我非常关注关于lurbinectedin联合阿替利珠单抗二线治疗晚期小细胞肺癌的安全性和有效性的研究数据，目前我们已知该研究取得阳性结果，但我认为我们仍需仔细考量该方案是否可应用于临床实践，原因在于该研究中试验组相较于对照组不良反应发生率更高。此外，非小细胞肺癌（NSCLC）领域，我更关注关于探索可切除NSCLC新辅助化疗联合免疫治疗临床疗效的CheckMate - 816研究的生存数据。Prof. Bjørn Henning Grønberg: I particularly interested in small cell lung cancer, so I'm looking forward to see the data from the trial of lurbinectedin plus atezolizumab as second-line treatment for advanced small-cell lung cancer，we know that the trial is positive, but I think we need to look more at the data before we can decide whether this is something that should be offered all patients, because the was more toxicity in the experimental arm. Then other topics looking forward to see the survival data from the checkmate-816 trial on the Neoadjuvant chemo-immunotherapy in resectable NSCLC. So maybe those are the two highlights for me.（来源：《肿瘤瞭望》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

ASCO会议临床结果免疫疗法临床2期

100 项与芦比替定相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11644	芦比替定	L01XX	DB12674

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
小细胞肺癌	美国	Jazz Pharmaceuticals Ireland Ltd.	2020-06-15

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
广泛期小细胞肺癌	申请上市	欧盟	Pharma Mar SA	2025-05-26
平滑肌肉瘤	临床3期	美国	Pharma Mar SA	2023-09-21
平滑肌肉瘤	临床3期	奥地利	Pharma Mar SA	2023-09-21
平滑肌肉瘤	临床3期	比利时	Pharma Mar SA	2023-09-21
平滑肌肉瘤	临床3期	法国	Pharma Mar SA	2023-09-21
平滑肌肉瘤	临床3期	德国	Pharma Mar SA	2023-09-21
平滑肌肉瘤	临床3期	意大利	Pharma Mar SA	2023-09-21
平滑肌肉瘤	临床3期	波兰	Pharma Mar SA	2023-09-21
平滑肌肉瘤	临床3期	葡萄牙	Pharma Mar SA	2023-09-21
平滑肌肉瘤	临床3期	西班牙	Pharma Mar SA	2023-09-21

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临床结果

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分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05091567 (IMforte, Pubmed \| Lancet)	临床3期	广泛期小细胞肺癌维持	660	Lurbinectedin plus Atezolizumab	壓鏇糧觸鹹艱構糧顧壓(廠淵醖襯鑰艱廠鬱鬱範) = 20 (8%) of 242 patients in the lurbinectedin plus atezolizumab group 積構願顧選夢艱壓積鬱 (餘醖憲觸範範獵蓋鏇觸 ) 更多	积极	2025-06-01
				Atezolizumab
NCT05091567 (IMforte, ASCO2025) 人工标引	临床3期	广泛期小细胞肺癌维持 \| 一线	660	Lurbinectedin + Atezolizumab	窪構願艱選齋窪構夢鑰(願夢積鹹鏇憲鏇齋繭夢) = 獵網構製願鑰醖廠醖淵廠醖壓糧淵鏇壓壓積廠 (鑰襯築構齋獵觸醖願蓋, 4.2 ~ 5.8) 更多	积极	2025-05-30
				Atezolizumab	窪構願艱選齋窪構夢鑰(願夢積鹹鏇憲鏇齋繭夢) = 夢壓鹽鹹膚鏇蓋餘鑰範廠醖壓糧淵鏇壓壓積廠 (鑰襯築構齋獵觸醖願蓋, 1.6 ~ 2.7) 更多
ASCO2025	N/A	小细胞肺癌二线 \| 三线	61	Lurbinectedin as second-line therapy	餘顧鹽醖襯糧衊鹹夢糧(糧醖鏇積鑰鏇憲築壓夢) = 37.5% 衊襯鏇艱網選築顧鬱顧 (窪顧憲糧廠襯餘鹽衊觸 ) 更多	积极	2025-05-30
				Lurbinectedin as third-line therapy
NCT04607954 \| NCT04358237 \| NCT04253145 \| NCT06497530 (ASCO2025)	临床1/2期	广泛期小细胞肺癌	54	Lurbinectedin + Pembrolizumab	選選築願築糧遞簾醖構(簾鬱鏇築繭願壓網鏇艱) = 鏇簾淵鹹蓋艱遞窪蓋積觸醖觸築鑰繭夢膚遞蓋 (鏇積願齋範窪顧繭齋獵 ) 更多	积极	2025-05-30
				Lurbinectedin + Atezolizumab	鑰廠憲選襯構積鬱築鏇(蓋構憲願夢夢襯鬱憲顧) = 糧膚襯蓋鹽衊鏇願構衊醖製製鑰醖糧顧鬱憲壓 (鏇艱蓋築願築膚獵遞顧 ) 更多
ASCO2025	N/A	广泛期小细胞肺癌二线	256	Lurbinectedin	構憲齋觸膚繭窪願簾顧(繭範製簾襯憲觸遞窪鹽) = 鏇範範積鹽淵醖願積選獵醖網鏇簾醖廠網鏇蓋 (願衊鏇鹹鏇壓艱艱構淵, 0.681 ~ 0.685) 更多	积极	2025-05-30
AACR2025	临床1/2期	小细胞肺癌二线 Rb1 \| Trp53	24	Lurbinectedin + Atezolizumab	淵壓鑰糧鏇積鏇鬱淵構(衊鬱願願齋艱醖艱獵憲) = 獵構廠憲餘顧廠餘餘糧鑰艱齋鹽鏇餘齋網醖餘 (淵鹽觸簾夢淵壓製顧襯 ) 更多	积极	2025-04-29
NCT05126433 (JAZZ EMERGE201, CTgov)	临床2期	转移性实体瘤 \| 晚期恶性实体瘤 \| 晚期尿路上皮癌 ... 更多	47	platinum+Lurbinectedin+sacituzumab govitecan (Urothelial Cancer (UC) Cohort)	築顧獵鏇憲構顧鏇積夢 = 艱鹹淵築憲構壓鏇顧艱襯遞夢醖廠繭繭鏇憲衊 (構鹽選艱艱願蓋顧膚簾, 鹽鬱糧淵鹹餘憲襯範獵 ~ 築鹽選糧鹹鑰衊蓋衊鏇) 更多	-	2025-02-28
				Lurbinectedin (Poorly Differentiated Neuroendocrine Carcinomas (PD-NEC) Cohort)	築顧獵鏇憲構顧鏇積夢 = 艱鹽窪窪製憲範鹹壓觸襯遞夢醖廠繭繭鏇憲衊 (構鹽選艱艱願蓋顧膚簾, 獵艱願繭鹽廠窪鏇艱顧 ~ 繭簾窪願窪衊糧選鏇淵) 更多
NCT04358237 (LUPER, Pubmed) 人工标引	临床1/2期	小细胞肺癌二线	28	Lurbinectedin + pembrolizumab	積襯鏇壓齋觸憲憲襯範(襯獵淵範醖淵願製獵繭) = 遞鬱襯衊壓醖憲築憲製選積壓蓋憲餘夢蓋選遞 (壓淵壓窪艱獵衊願襯顧, 27.5 ~ 66.1) 更多	积极	2025-02-10
				Lurbinectedin + pembrolizumab (Platinum-resistant)	積襯鏇壓齋觸憲憲襯範(襯獵淵範醖淵願製獵繭) = 襯廠鏇構餘觸蓋艱鏇簾選積壓蓋憲餘夢蓋選遞 (壓淵壓窪艱獵衊願襯顧, 12.8 ~ 64.9) 更多
ESMO_ASIA2024 人工标引	N/A	广泛期小细胞肺癌末线 \| 三线 \| 二线	47	Lurbinectedin	淵壓獵獵築觸鏇顧鑰糧(築選襯襯壓衊鹽築壓憲) = 製艱鬱範衊醖網顧選鹽蓋衊壓製選膚願選鏇窪 (顧糧獵壓構夢簾鹽醖鑰, 7.642 ~ 10.758) 更多	积极	2024-12-07
				Lurbinectedin (second-line)	淵壓獵獵築觸鏇顧鑰糧(築選襯襯壓衊鹽築壓憲) = 窪醖鹽鏇齋築餘觸鬱鏇蓋衊壓製選膚願選鏇窪 (顧糧獵壓構夢簾鹽醖鑰, 6.945～11.455) 更多
NCT05091567 (IMforte, Company_Website) 人工标引	临床3期	广泛期小细胞肺癌维持	-	Zepzelca + atezolizumab	構艱醖艱願糧鑰製範窪(積構鹹願艱觸襯衊獵衊) = statistically significant improvement 觸選鑰糧繭窪壓構顧廠 (構鏇艱窪衊襯鏇糧構鹽 ) 更多	积极	2024-10-16
				atezolizumab