Phase 1 Trial of Nab-Paclitaxel PIPAC (Pressurized Intraperitoneal Aerosolized Chemotherapy) Given in Combination With Second-Line Therapy for Gastric Cancer With Peritoneal Metastases

This phase I trial tests the safety, side effects and best dose of nab-paclitaxel pressurized intraperitoneal aerosolized chemotherapy (PIPAC) in combination with second-line chemotherapy, paclitaxel and ramucirumab, and tests how well they work in treating stomach cancer that has spread from where it first started to the tissue that lines the abdominal wall and organs (peritoneal metastases). Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. PIPAC delivers chemotherapy, such as nab-paclitaxel, that has been turned into a fine mist (aerosolized) at a high pressure directly into the abdominal cavity. Aerosolized chemotherapy delivered directly into the peritoneal space has been shown to deliver higher drug concentrations to the tumor. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Giving nab-paclitaxel PIPAC in combination with paclitaxel and ramucirumab may be safe, tolerable, and/or effective in treating gastric cancer patients with peritoneal metastases.

开始日期2025-10-17

申办/合作机构

City of Hope National Medical Center

[+1]

NCT06616584 / Not yet recruiting临床2/3期IIT

A Randomized Phase II/III Study of Docetaxel and Ramucirumab With or Without Cemiplimab for Participants Previously Treated With Platinum-Based Chemotherapy and Immunotherapy for Stage IV or Recurrent Non-Small Cell Lung Cancer (Lung-MAP Non-Matched Sub-Study)

This phase II/III Expanded Lung-MAP treatment trial compares the effect of adding cemiplimab to docetaxel and ramucirumab versus docetaxel and ramucirumab alone in treating patients with non-small cell lung cancer that is stage IV or that has come back after a period of improvement (recurrent). Cemiplimab is a monoclonal antibody that stimulates the immune system by blocking the PD-1 pathway. Tumors use the PD-1 pathway to escape attacks from the immune system. By blocking the PD-1 pathway, cemiplimab may help the immune system recognize and attack tumor cells. Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Adding cemiplimab to usual treatment, docetaxel and ramucirumab, may kill more tumor cells compared to docetaxel and ramucirumab alone in treating patients with stage IV or recurrent non-small cell lung cancer.

开始日期2025-07-11

申办/合作机构

SWOG

[+2]

NCT06680622 / Not yet recruiting临床2期IIT

Bemarituzumab in Patients With FGFR2b-positive Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction, Who Failed at Least One Prior Line of Palliative Chemotherapy - The IKF-AIO Phase IIa BEMARA Trial

The goal of this clinical trial is to evaluate if bemarituzumab in combination with different standard of care chemotherapies enhance tumor response in patients with FGFR2b-positive advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. The main questions are:
How do patients respond to these treatments? How is the overall and the progression-free survival rate with these treatments? How is the disease control rate with these treatments? How long is the duration of response and disease stabilization with these treatments? How is the safety with these treatments? How is the quality of life with these treatments?
Patients will be allocated to one of three possible treatment cohorts according to investigator's decision and current standard of care:
Bemarituzumab with cohort 1: irinotecan cohort 2: paclitaxel plus ramucirumab cohort 3: trifluridine/tipiracil

开始日期2024-12-01

申办/合作机构

Institut fr Klinische Krebsforschung IKF GmbH

[+3]

100 项与雷莫西尤单抗相关的临床结果

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100 项与雷莫西尤单抗相关的转化医学

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100 项与雷莫西尤单抗相关的专利（医药）

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1,322

项与雷莫西尤单抗相关的文献（医药）

2025-12-01·Journal of Gastrointestinal Cancer

Network Meta-analysis of Randomized Controlled Trials in Patients with Previously Treated Advanced Gastric or Gastroesophageal Junction Cancer: Comparisons Involving Ramucirumab

Review

作者: Taipale, Kaisa ; Paine, Abby ; Gupta, Palvi ; Liepa, Astra M ; D'yachkova, Yulia ; Earley-Valovic, Veronika ; Goel, Rajat

PURPOSE:

With relatively few direct comparisons among treatment options for previously treated advanced gastric cancer or gastroesophageal junction (GEJ) cancer, network meta-analysis (NMA) may inform evidence-based decision-making. Ramucirumab plus paclitaxel (RAM + PTX) is a preferred regimen in guideline recommendations. NMA of key outcomes may further characterize the relative clinical value of RAM + PTX.

METHODS:

A systematic literature review of randomized controlled trials of adult patients with previously treated advanced gastric/GEJ cancer informed a NMA which compared overall survival, progression-free survival, and discontinuations due to adverse events. Comparisons were reported relative to placebo/best supportive care (BSC) when possible, otherwise relative to RAM + PTX.

RESULTS:

The base-case NMA focused on second-line treatment only, from 19 of 28 studies identified. For overall survival, seven of 16 regimens were favorable relative to placebo/BSC, with RAM + PTX as the most favorable. For progression-free survival, five of 14 regimens were unfavorable relative to RAM + PTX. For discontinuations due to adverse events, two of 13 regimens were similar to placebo/BSC: ramucirumab monotherapy and fluorouracil; relative to RAM-PTX, all regimens were similar except ramucirumab monotherapy which was favorable and irinotecan + cisplatin which was unfavorable.

CONCLUSION:

This NMA of trials of previously treated gastric/GEJ cancer suggests that RAM + PTX has one of the more favorable clinical profiles.

2024-12-01·Drugs-Real World Outcomes

Clinical Significance of Prior Ramucirumab Use on the Effectiveness of Nivolumab as the Third-Line Regimen in Gastric Cancer: A Multicenter Retrospective Study

Article

作者: Ishida, Michihiro ; Kono, Yoshiyasu ; Choda, Yasuhiro ; Hirata, Shoichiro ; Kawano, Seiji ; Miyahara, Koji ; Kawahara, Yoshiro ; Abe, Makoto ; Otsuka, Motoyuki ; Nakagawa, Masahiro ; Obayashi, Yuka ; Iwamuro, Masaya ; Hamada, Kenta

BACKGROUND AND OBJECTIVE:

Because vascular endothelial growth factor inhibition has been suggested to improve immune cell function in the cancer microenvironment, we examined whether using ramucirumab (RAM) before nivolumab usage is more effective in advanced gastric cancer.

METHODS:

This was a multicenter retrospective observational study. We analyzed patients who received nivolumab monotherapy as the third-line regimen for unresectable advanced or recurrent gastric cancer between October 2017 and December 2022. They were divided into the RAM (RAM-treated) group and the non-RAM (non-treated) group according to the RAM usage in the second-line regimen. The primary outcome was to compare the overall survival after nivolumab administration in the third-line regimen between the RAM and non-RAM groups.

RESULTS:

Fifty-two patients were included in the present study: 42 patients in the RAM group and ten patients in the non-RAM group. The median overall survival was significantly longer in the RAM group than in the non-RAM group (8.5 months vs 6.9 months, p < 0.05). In the RAM group, patients without peritoneal metastasis had significantly better median overall survival than those with peritoneal metastasis (23.8 months vs 7.7 months, p = 0.0033). Multivariate Cox-proportional hazards analyses showed that the presence of peritoneal metastasis (hazard ratio, 2.4; 95% confidence interval 1.0-5.7) alone was significantly associated with overall survival in the RAM group.

CONCLUSIONS:

The use of RAM prior to nivolumab monotherapy may contribute to prolonged survival in patients with gastric cancer, especially those without peritoneal metastasis.

2024-12-01·JTO clinical and research reports

S1701, A Randomized Phase 2 Trial of Carboplatin-Paclitaxel With and Without Ramucirumab in Patients With Locally Advanced, Recurrent, or Metastatic Thymic Carcinoma

Article

作者: Tsao, Anne S ; Koczywas, Marianna ; Zhao, Ying-Qi ; Edelman, Martin J ; Tu, Janet ; Ma, Barbara T ; Gandara, David R ; Kelly, Karen L ; Riess, Jonathan ; Redman, Mary W ; Tanvetyanon, Tawee ; Gray, Jhanelle E ; Hsieh, Ming-Hui

Introduction:

Thymic carcinoma is a rare and aggressive malignancy with few treatment options. Preclinical studies suggested that targeting the angiogenic pathway may be beneficial in this disease.

Methods:

This randomized phase 2 trial enrolled patients with unresectable, locally advanced, recurrent, or metastatic thymic carcinoma. Patients were randomized to receive carboplatin-paclitaxel with or without ramucirumab. The primary end point was progression-free survival (PFS) and secondary end points included response by Response Evaluation Criteria in Solid Tumors, disease control, toxicity, and overall survival. The primary analysis was done using a one-sided 10%-level log-rank test. Target sample size was 66 patients.

Results:

Between 2018 and 2022, 21 patients enrolled to ramucirumab plus carboplatin-paclitaxel (RCP, n = 8) and to the control arm (carboplatin-paclitaxel [CP], n = 13) with one patient on CP not meeting eligibility criteria. Owing to slow accrual, the study was terminated early by the Data and Safety Monitoring Board. Of the 20 eligible patients, eight on RCP and nine on CP received protocol treatment. PFS was not statistically different (hazard ratio = 0.51, 80% confidence interval [CI]: 0.24-1.09, p = 0.13). There were no grade 4 or higher treatment-related adverse events with RCP, although 50% experienced grade 3 adverse events, in which one patient had a grade 3 thromboembolic event. Among nine assessable patients for toxicity on CP, one patient (11%) encountered grade 4 neutropenia and one patient (11%) reported grade 3 thromboembolic events. Response rates favored the RCP arm, with an 88% (seven of eight, 80% CI: 59%-99%) response rate compared with 40% (four of 10, 80% CI: 19%-65%) on CP arm (p = 0.04). Disease control rate was higher in the RCP arm (100% versus 70%, p = 0.09). At the time of analysis, as only one death has been reported, overall survival remains immature.

Conclusions:

Accrual to this population is challenging, and the study was closed early because of feasibility. Although PFS was not statistically better with RCP, the hazard ratio was 0.51 and the lack of significance was likely due to small sample sizes. Notably, addition of ramucirumab to CP led to higher response rates than CP alone. Future research should consider exploring larger multicenter trials and other combinations to improve outcomes. Challenges in enrollment emphasize the need for innovative strategies and larger collaborations in rare malignancies such as thymic carcinoma.

658

项与雷莫西尤单抗相关的新闻（医药）

2024-12-17

·今日头条

胃癌患者必须知道的明星靶点-CLDN18.2，抗癌路上的精准武器！

胃癌（GC）在全球范围内属于第五大常见癌症类型。伴随分子靶向治疗的兴起，针对HER2靶点的曲妥珠单抗，已然成为HER2阳性胃癌的一线治疗用药。另外，针对血管内皮生长因子受体2的单克隆抗体雷莫芦单抗与紫杉醇联合运用，在二线治疗过程中也展现出了对患者生存状况的改善作用。而用于PD-1的纳武单抗（Nivolumab）则获批应用于三线或后续治疗阶段。不过，对于那些不可切除或者已处于转移性晚期的胃癌患者而言，其预后状况依旧难以令人满意。所以，积极开发新型治疗策略已然成为当下极为紧迫的任务。除了上面提到的靶点和药物外，一个暴露于胃和胃食管结合部腺癌（GEJ）表面，极具治疗潜力的靶点——CLDN18.2，也是胃癌患者务必知晓的。特别是随着全球首款 CLDN18.2 靶向药佐贝妥昔单抗（Zolbetuximab）震撼上市之后，更是使得CLDN18.2这一明星靶点再度引起广泛关注。一、胃癌患者必须知道的明星靶点——CLDN18.2 CLDN是体内上皮细胞粘附所必需的，对屏障功能至关重要，它是一个至少包含27种跨膜蛋白的家族，在信号转导和肿瘤发生中发挥作用，如肿瘤细胞的生长和存活、肿瘤增殖、转移和肿瘤组织中的癌症干细胞等。其中，1998年发现的CLDN18.2蛋白是在正常和恶性胃粘膜上皮细胞中，表达的紧密连接蛋白中的一种分子。在正常胃黏膜上皮中，CLDN18.2（Claudin18.2）表达严格局限于除胃干细胞区以外的胃黏膜分化上皮细胞。但在胃癌、胃食管结合部腺癌（GEJ）、食管癌、结肠癌、胰腺癌、乳腺癌、肝癌、卵巢癌、非小细胞肺癌等某些恶性肿瘤中，它也普遍表达。值得注意的是，在正常组织中，组织粘附复合物内的CLDN18.2表位完全无法接近；然而，在恶性转化时，细胞粘附被破坏，CLDN18.2表位暴露在胃和GEJ（G/GEJ）腺癌细胞表面，使其成为一个有希望的靶点，尤其在消化系统肿瘤中（如胃癌、胃食管结合部癌、食管癌和胰腺癌）异常过表达，比如，在胃癌或胃食管结合部癌中，在高达70%-80%的胃癌或胃食管结合部癌患者，以及60%的胰腺癌患者可检测到Claudin 18.2的高度表达。因此确诊胃癌、食管癌、胰腺癌等消化道肿瘤后，除了检测HER2、PD-L、MET等靶点外，还要再检测下是否存在Claudin 18.2。 ▼晚期胃癌CLDN18.2靶向治疗的发展 ▲图源“MDPI”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除二、针对CLDN18.2靶点的抗癌新药及新技术截至 2023 年 8 月，Clinical Trials.gov (NCT) 网站上，共有 43 项正在进行的针对CLDN18.2的临床试验，包括CAR-T疗法、ADC（抗体-药物偶联物）药物、双特异性抗体 (BsAbs)等。（一）全球首款CLDN18.2靶向疗法-佐贝妥昔单抗震撼上市，显著延长生存期！ 2024年3月26日，佐贝妥昔单抗（Zolbetuximab，VYLOY，代号IMAB362）获日本厚生劳动省(MHLW)批准上市，用于CLDN18.2阳性、不可切除、晚期或复发性胃癌的治疗，它是首个同时也是目前唯一获得世界监管机构批准的CLDN18.2靶向疗法。全球知名期刊《自然医学》报道了“ 佐贝妥昔单抗的Ⅲ期GLOW临床研究（NCT03653507） ”的惊艳数据，本次共入组507例既往未接受过治疗的CLDN18.2阳性、HER2阴性的局部晚期或转移性胃癌或胃食管交界癌患者，将其分为两组，即佐贝妥昔单抗组（接受佐贝妥昔单抗+CAPOX治疗）、安慰剂组（接受安慰剂+CAPOX治疗）。结果显示如下： 1、中位无进展生存期（PFS）：接受佐贝妥昔单抗治疗的患者，PFS显著延长，中位PFS分别为 8.21个月（佐贝妥昔单抗组） vs 6.80个月（安慰剂组）（详见下图）。12个月PFS率分别为 35% （佐贝妥昔单抗组） vs 19% （安慰剂组）；24个月PFS率分别为 14% （佐贝妥昔单抗组） vs 7% （安慰剂组）。 ▲图源“nature”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 2、中位总生存期（OS）：佐贝妥昔单抗组患者的OS在统计学上显著延长，中位OS分别为 14.39个月（佐贝妥昔单抗组） vs 12.16个月（安慰剂组）（详见下图）。12个月的OS率分别为 58% （佐贝妥昔单抗组） vs 51% （安慰剂组）；24个月的OS率分别为 29% （佐贝妥昔单抗组） vs 17% （安慰剂组）。 ▲图源“nature”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除（二）北肿公布CT041第1阶段试验最终结果：疾病控制率高达96.1% CT041（satri-cel）是一款靶向Claudin18.2（CLDN18.2）的自体CAR-T细胞（嵌合抗原受体T细胞）。近日，北肿研发团队公布了关于“ CT041-CG4006的1期临床试验（NCT03874897）的最终结果 ”。本次共入组98例CLDN18.2阳性晚期胃肠道肿瘤患者，入组接受不同剂量的CT041（即CAR-T细胞）回输治疗，治疗剂量分别为2.5×108（89例患者）、3.75×108（6例患者）、5.0×108（3例患者），中位随访时间为32.4个月。结果显示：在全部98例患者中，91.8%（90例）基线有靶病灶，治疗后70例患者出现不同程度的肿瘤缩小，总缓解率为38.8% ，疾病控制率（DCR）高达91.8% ，中位总生存期（OS）长达8.8个月（95% CI：7.1,10.2），中位无进展生存期（PFS）为4.4个月（95% CI：3.7,6.6）。 ▼CT041治疗后疗效的泳道图 ▲图源“nature medicine”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除三、更多在研的Claudin18.2的新药/新技术除了上面提到的佐贝妥昔单抗、CT041（CAR-T）外，目前国内外还有多款在研的针对Claudin18.2的新药获新疗法，包括但不限于以下几类： 1、TQB2103 TQB2103是中国生物制药自主研发的针对CLDN18.2的ADC药物。TQB2103与表面表达CLDN18.2的肿瘤细胞结合后，被内化并运输到溶酶体，在溶酶体中释放细胞毒性有效载荷，从而通过脱氧核糖核酸（DNA）损伤选择性杀死肿瘤细胞。通过旁观者效应，它可以杀死相邻的阴性肿瘤细胞。目前正在进行一项I期临床试验，评估TQB2103注射液对晚期癌症患者的耐受性、安全性和有效性（NCT05867563）。 2、ASKB589 ASKB589是一种人源化抗CLDN18.2IgG1mAb，具有高亲和力和增强的ADCC。已公布ASKB589对晚期实体瘤患者的I/II期剂量递增和扩展研究的初步结果（NCT04632108）。本研究评估了ASKB589单药治疗（A部分）和与化疗联合治疗（B部分）的最大耐受剂量（MTD）、安全性和耐受性、PK、PD和疗效。在A部分9名可评估患者（≥10mg/kgASKB589）中，5名患者（45%）的肿瘤缩小，而2名患者获得部分缓解（PR）。此外，6名患者病情稳定（SD），疾病控制率（DCR）高达89%。在B部分12名可评估患者（≥6mg/kgASKB589）中，所有患者的肿瘤均缩小，9名患者获得PR，客观缓解率（ORR）高达75%，DCR疾病控制率（DCR）更是达到100%。综上，ASKB589显示出高达20mg/kg剂量的可控安全性和良好的抗肿瘤活性。 3、IMC002 IMC002是一种基于抗CLDN18.2VHH抗体的自体CAR-T细胞疗法，具有高特异性，与CLDN18.2无交叉反应。一项1期、开放标签、多中心、剂量递增研究旨在评估IMC002对CLDN18.2阳性胃肠道肿瘤患者的安全性、可行性和初步疗效，包括但不限于晚期胃癌、食管胃交界处腺癌和晚期胰腺癌（NCT05946226）。约9-18名CLDN18.2阳性晚期胃肠道肿瘤患者将依次纳入三个剂量递增队列，以评估自体IMC002治疗的安全性和可行性。患者入组后将接受白细胞分离术和IMC002产品制备。如果病情迅速进展，患者可按照研究者的决定接受桥接疗法。在接受环磷酰胺、氟达拉滨和白蛋白紫杉醇淋巴细胞清除治疗后，患者将被分配到三个剂量递增组接受CAR-T细胞治疗。 4、SYSA1801 SYSA1801是一种靶向CLDN18.2的ADC，可递送微管抑制剂MMAE。临床前研究表明，SYSA1801在表达CLDN18.2的胃癌、胰腺癌和肺癌的多种细胞系和PDX中表现出显著的体内和体外抗肿瘤活性。I期试验纳入的33名耐药复发性实体瘤患者中，26名（78.8%）患有胃癌。在第I部分中，患者接受了高达3mg/kg的SYSA1801。在17名可评估的胃癌患者中，ORR为47.1%（8名患者为PR），DCR为64.7%（3名患者为SD）。SYSA1801的最佳剂量正在探索中（NCT05009966）。 5、LM-302 LM-302（TPX-4589）是一种针对CLDN18.2而开发的新型ADC，由重组人源化抗CLDN18.2IgG1mAb（LM-102）与细胞毒性有效载荷MMAE偶联而成。根据临床前数据，在高表达和低表达的胃和胰腺CLDN18.2肿瘤模型中，LM-302体外有效抑制肿瘤细胞增殖，体内减少肿瘤生长。此外，在GC肿瘤模型中，与佐贝妥昔单抗相比，LM-302表现出更好的内化和疗效。目前，针对CLDN18.2阳性晚期实体瘤患者的LM-302的I期研究正在评估中（NCT05001516）。此外，目前正在进行一项I/II期、开放标签、多中心研究，旨在评估LM-302联合特瑞普利单抗（抗PD-1抗体）对晚期实体瘤患者的安全性和耐受性（NCT05188664）。四、小编寄语 CLDN18.2作为胃癌治疗领域的新兴靶点，为胃癌患者带来了新的希望。随着研究的不断深入和临床实践的逐步积累，基于CLDN18.2的治疗药物和方案将不断优化和完善。未来，我们有望看到更多高效、低毒的CLDN18.2靶向治疗药物问世，并且在联合治疗模式的探索上取得更大突破，从而显著提高胃癌患者的治疗效果，改善患者的生存质量和预后，为胃癌的攻克迈出坚实的一步。胃癌患者及其家属应该与医生积极沟通，了解CLDN18.2靶点相关知识以及其在治疗方案中的应用可能性，共同参与到胃癌的精准治疗决策过程中，以争取更好的治疗效果和生存机会。五、参考资料 [1]Inamoto R,et al.Claudin18. 2 in advanced gastric cancer[J]. Cancers, 2023, 15(24): 5742. https://www.mdpi.com/2072-6694/15/24/5742 [2]Shah M A,et al.Zolbetuximab plus CAPOX in CLDN18. 2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial[J]. Nature medicine, 2023, 29(8): 2133-2141. https://www-nature-com.libproxy1.nus.edu.sg/articles/s41591-023-02465-7 [3]Qi C,et al.Claudin18. 2-specific CAR T cells in gastrointestinal cancers: phase 1 trial final results[J].Nature Medicine, 2024:1-11. https://www-nature-com.libproxy1.nus.edu.sg/articles/s41591-024-03037-z 本文为全球肿瘤医生网原创，未经授权严禁转载

2024-12-17

·echemi

Eli Lilly’s Pirtobrutinib Joins the Race as BTK Competition Heats Up

On December 16, Innovent Biologics and Eli Lilly announced a collaboration agreement for the non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor, pirtobrutinib, in mainland China. Under this agreement, Innovent Biologics will handle the import, sales, promotion, and distribution, while Eli Lilly will manage R&D and post-market medical affairs. On October 29, Eli Lilly’s pirtobrutinib received approval from the National Medical Products Administration (NMPA) for treating relapsed or refractory mantle cell lymphoma (MCL) in adults who have previously received BTK inhibitor treatments. Currently, the domestic market has five approved BTK inhibitors, including ibrutinib, zanubrutinib, ocatabrutinib, and acabrutinib. Sanofi’s Tolebrutinib and Rilzabrutinib are in Phase III clinical trials, while CT-1530 from Shouyao Holdings is in Phase II. The robust development of BTK inhibitors indicates potential market changes. BTK inhibitors work by targeting the BCR signaling pathway, binding to BTK, inhibiting its phosphorylation, and inducing apoptosis, effectively managing B-cell malignancies. Before BTK inhibitors, lymphoma treatments were limited to chemotherapy, anti-CD20 antibodies, and radiotherapy. Ibrutinib, the first BTK inhibitor, revolutionized B-cell cancer treatment since its 2013 debut and was approved in China in 2017. However, sales of ibrutinib have slowed due to competition from similar drugs. Zanubrutinib, developed by BeiGene, reached $1.297 billion in global sales in 2023, marking the first domestic drug to achieve such success, but it now faces increasing competition. Pirtobrutinib, as the first and only non-covalent BTK inhibitor, intensifies competition in this niche market. It shows potential to overcome resistance to covalent BTK inhibitors and offers a new option for relapsed/refractory MCL patients. To highlight its efficacy, Eli Lilly conducted a head-to-head study in the BRUIN MCL-321 trial. By 2030, pirtobrutinib is projected to capture 60% of the chronic lymphocytic leukemia market, equating to $3 billion in annual sales. With advancing technology and new drug development, the BTK market is expanding rapidly. According to Frost & Sullivan, the global BTK market could reach $20 billion by 2025 and $26.1 billion by 2030. In China, the market size is expected to reach RMB 13.1 billion by 2025 and RMB 22.5 billion by 2030. The growing BTK market has attracted numerous pharmaceutical companies. At least 20 BTK inhibitors are in clinical trials domestically, with Shouyao Holdings, Hengrui Medicine, and Hezheng Pharmaceutical leading the way. Ibrutinib’s core patent will expire on December 28, 2026, and at least 10 companies are preparing generics. This will lead to fierce competition among original drugs, domestic innovations, and generics. BeiGene’s zanubrutinib remains a key product, but new competitors like pirtobrutinib pose challenges. The success of pirtobrutinib in China’s market is worth monitoring. Originally developed by Redx Pharma and acquired by Loxo Oncology, pirtobrutinib was purchased by Eli Lilly for $8 billion in 2019. In March 2022, Innovent Biologics secured Chinese commercialization rights for pirtobrutinib with an initial payment of $45 million. The partnership between Innovent Biologics and Eli Lilly began in 2015 and has expanded through multiple projects. Despite setbacks like sintilimab’s rejection by the U.S. FDA in 2022, their collaboration continues with other initiatives. Their 2019 cooperation on IBI362, a dual GLP-1R and GCGR agonist, is in Phase II/III trials for Type 2 diabetes and weight loss. In March 2022, Eli Lilly’s ramucirumab was approved in China, granting Innovent Biologics exclusive commercialization rights. Additionally, they collaborate on selpercatinib, a RET inhibitor for gene fusion tumors. The cooperation and competition between domestic and multinational pharmaceutical companies are becoming a norm. This model offers a win-win strategy for navigating the global market.

上市批准并购临床3期临床2期引进/卖出

2024-12-16

·健识局

礼来又拉了信达一把

12月16日，礼来发布公告，和信达生物就BTK抑制剂匹妥布替尼达成合作，信达生物将负责匹妥布替尼在中国大陆的销售。这个决定应该是早就做好的。2022年3月，信达从礼来手里拿下两款肿瘤产品的中国销售权益，当时匹妥布替尼还没上市，但其在中国大陆的商业优先谈判权已经到了信达手里。今年10月，匹妥布替尼在国内获批上市，用于既往接受过至少两种系统性治疗的复发或难治性套细胞淋巴瘤成人患者。这款药物想象空间不小，礼来预测其2030年年销售额能达到30亿美元，信达于是选择再度与礼来牵手。事实上，礼来和信达已经是第六次合作。早在2012年，礼来亚洲基金就曾为信达提供资金。后续礼来又引进了信达生物的PD-1，还先后给了信达多款药物的权益。又给产品又给钱，说信达这一路缺不了礼来也不算夸张。如今，信达距离2027年国内营收200亿元的目标又近了一步。被卖掉的潜力产品本次交易主角匹妥布替尼，是一款第三代BTK抑制剂，相比于前两代产品最大的亮点在于对抗耐药性。 BTK抑制剂在血液瘤领域广泛应用，市场规模超百亿美元，诞生了伊布替尼、泽布替尼等重磅炸弹药物，但BTK抑制剂耐药问题无法避免。有研究显示，伊布替尼用药4年后约有19%的慢性淋巴细胞白血病患者会发生疾病进展。匹妥布替尼设计思路与前两代BTK抑制剂不同，作用位点不再是与C481结合，而是以非共价结合BTK，对前两代BTK抑制剂耐药患者仍然有效。在名为BRUIN的1/2期研究中，匹妥布替尼展现出了惊艳的效果，在既往接受过BTK抑制剂治疗、治疗基线中位值为四线的患者中，总缓解率（ORR）为81.6%，中位无进展生存期（mPFS）为19.4个月。 2023年1月，匹妥布替尼在美国获批上市，成为全球首个且唯一获批的非共价BTK抑制剂。目前，匹妥布替尼已经获批治疗套细胞淋巴瘤、慢性淋巴细胞白血病、小淋巴细胞性淋巴瘤。2024年上半年，匹妥布替尼全球销售额达到1.42亿美元，增长迅猛。礼来也对匹妥布替尼充满期待，在2023年财报中，礼来将其看成新的增长引擎之一。预计2030年匹妥布替尼将在慢淋市场占据60%市场份额，对应30亿美元的年销售额。为了证明自身实力，也为了进一步打开市场想象空间，礼来还在BRUIN CCL-321的临床试验，头对头挑战伊布替尼、泽布替尼、阿卡替尼三款BTK抑制剂，预计2025年底将会获得顶线数据。如果匹妥布替尼真能成功以一敌三，那等着它的将会是一个巨大的市场。这么一款潜力产品，礼来为什么要把中国销售权益交给信达生物？礼来为何选择信达？礼来的选择其实不算意外。在2012年6月，信达生物获得的3000万美元B轮融资就由礼来亚洲基金领投。2015年起，礼来和信达生物频繁进行管线上的合作，信达将自研产品PD-1授权给了礼来，同时也引进礼来的产品进入中国。又给钱又给产品，可以说没有礼来，就难有今天的信达。 2022年3月，礼来与又将雷莫西尤单抗注射液、塞普替尼胶囊在国内的商业化权利给了信达。匹妥布替尼的商业优先谈判权也一并给了信达生物。可以看出，礼来从头到尾就没想过自建销售团队在国内卖这款产品。这不难理解。虽然礼来在代谢、自免领域实力强悍，有多款重磅药物，但在一众跨国大药企中，礼来的肿瘤领域并不算突出，仅有CDK4/6抑制剂阿贝西利这一大单品。眼下，礼来在中国的重心也基本放在了代谢领域。今年10月，礼来表示将投资约15亿元用于苏州工厂产能升级，扩大2型糖尿病和肥胖创新药物的生产规模。至于肿瘤，本就不是礼来当下的重点。礼来中国官网显示，其肿瘤领域共有信迪利单抗、利妥昔单抗、塞普替尼胶囊、雷莫西尤单抗、贝西利片、呋喹替尼胶囊、注射用盐酸吉西他滨、注射用培美曲塞二钠8款产品，其中前四款产品的商业化权益都在信达手里。为了这一款药物自建血液瘤销售团队，显然性价比不高。更何况，礼来在国内的销售能力并不算强悍。有业内人员告诉健识局：“礼来产品力很强这是无可置疑的，但其销售比较佛性，指标定的不算激进。” 相比之下，信达的销售能力是有目共睹。截至2024年6月30日，信达拥有超3000人的销售团队。尤其是在血液瘤领域已经建立了完善的产品组合，涵盖信迪利单抗、利妥昔单抗、奥雷巴替尼、伊基奥仑赛注射液、匹妥布替尼片多款产品。不论是血液瘤领域的商业化能力还是广阔的渠道覆盖，信达生物都是礼来的优选。对于信达而言，产品线又多了一款潜力产品，公司2027年国内产品收入达到200亿元的目标变得更近了一步。撰稿丨方涛之编辑丨江芸贾亭运营｜廿十三插图｜视觉中国声明：健识局原创内容，未经许可请勿转载国家医保局公布2025工作重点；跨国械企中国区大裁员；第一三共投资11亿元国内建厂美国药店也不行了砍掉所有临床管线，又一跨国药企退出乙肝领域？

财报上市批准医药出海引进/卖出

100 项与雷莫西尤单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09371	雷莫西尤单抗	L01XC21	DB05578

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
不可切除的肝细胞癌	日本	Eli Lilly & Co.	2016-06-20
晚期胃癌	澳大利亚	Eli Lilly Australia Pty Ltd.	2015-07-23
转移性胃癌	澳大利亚	Eli Lilly Australia Pty Ltd.	2015-07-23
结直肠癌	欧盟	Eli Lilly Nederland BV	2014-12-19
结直肠癌	冰岛	Eli Lilly Nederland BV	2014-12-19
结直肠癌	列支敦士登	Eli Lilly Nederland BV	2014-12-19
结直肠癌	挪威	Eli Lilly Nederland BV	2014-12-19
肝细胞癌	欧盟	Eli Lilly Nederland BV	2014-12-19
肝细胞癌	冰岛	Eli Lilly Nederland BV	2014-12-19
肝细胞癌	列支敦士登	Eli Lilly Nederland BV	2014-12-19
肝细胞癌	挪威	Eli Lilly Nederland BV	2014-12-19
胃食管交界处恶性肿瘤	欧盟	Eli Lilly Nederland BV	2014-12-19
胃食管交界处恶性肿瘤	冰岛	Eli Lilly Nederland BV	2014-12-19
胃食管交界处恶性肿瘤	列支敦士登	Eli Lilly Nederland BV	2014-12-19
胃食管交界处恶性肿瘤	挪威	Eli Lilly Nederland BV	2014-12-19
转移性结直肠癌	欧盟	Eli Lilly Nederland BV	2014-12-19
转移性结直肠癌	冰岛	Eli Lilly Nederland BV	2014-12-19
转移性结直肠癌	列支敦士登	Eli Lilly Nederland BV	2014-12-19
转移性结直肠癌	挪威	Eli Lilly Nederland BV	2014-12-19
非小细胞肺癌	欧盟	Eli Lilly Nederland BV	2014-12-19

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
复发性非小细胞肺癌	临床3期	美国	Merck Sharp & Dohme Corp.	2023-03-14
复发性非小细胞肺癌	临床3期	美国	Eli Lilly & Co.	2023-03-14
进展期胃腺癌	临床3期	中国	信达生物制药（苏州）有限公司	2021-03-10
晚期肝细胞癌	临床3期	中国	美国礼来亚洲公司上海代表处	2017-06-13
晚期肝细胞癌	临床3期	中国	Eli Lilly & Co.	2017-06-13
晚期肝细胞癌	临床3期	中国香港	Eli Lilly & Co.	2017-06-13
晚期肝细胞癌	临床3期	中国香港	美国礼来亚洲公司上海代表处	2017-06-13
晚期肝细胞癌	临床3期	中国台湾	美国礼来亚洲公司上海代表处	2017-06-13
晚期肝细胞癌	临床3期	中国台湾	Eli Lilly & Co.	2017-06-13
腺癌	临床3期	中国	Eli Lilly & Co.	2017-03-02

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临床结果

适应症

分期

评价

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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


JPRN-jRCTs041180166 (WJOG9216G (RECAST), ESMO2024) 人工标引	临床2期	转移性结直肠癌一线	122	FOLFOXIRI pluRAMAM	齋鬱願襯遞獵窪鹽鹽廠(製簾範艱衊蓋鹽糧網廠) = 壓遞製選襯遞衊顧衊醖遞繭壓網範鏇遞繭壓餘 (構積願糧糧構鑰艱憲憲, 26.8 ~ 36.5)	不佳	2024-09-14
				8 cycles of FOLFOXIRI plus RAM followed by 5-FU/l-leucovorin plus RAM	齋鬱願襯遞獵窪鹽鹽廠(製簾範艱衊蓋鹽糧網廠) = 獵鹽鹽衊廠顧繭鏇壓積遞繭壓網範鏇遞繭壓餘 (構積願糧糧構鑰艱憲憲, 21.9 ~ 31.2)
NCT02443324 (JVDF, CTgov)	临床1期	腺癌 \| 膀胱尿路上皮癌 \| 局部晚期胃食管交界处腺癌 ... 更多	175	pembrolizumab+Ramucirumab (Cohort A)	淵襯鹽製壓觸選願廠遞(遞憲壓淵襯積齋遞蓋窪) = 蓋淵築餘範廠壓衊餘齋壓餘鹹鏇鹹築廠餘鏇憲 (糧鏇簾選廠窪齋製築蓋, 鏇鏇夢構範簾製齋襯網 ~ 鬱顧壓衊構膚廠遞鏇顧) 更多	-	2024-07-31
				pembrolizumab+Ramucirumab (Cohort C)	淵襯鹽製壓觸選願廠遞(遞憲壓淵襯積齋遞蓋窪) = 糧壓壓願壓鬱構襯築鏇壓餘鹹鏇鹹築廠餘鏇憲 (糧鏇簾選廠窪齋製築蓋, 糧繭艱壓選襯鹹製壓網 ~ 窪醖網窪齋觸遞鬱醖廠) 更多
NCT04915807 (KCSG ST21-06, ESMO_GI2024) 人工标引	N/A	胃腺癌 \| 胃食管交界处腺癌二线	444	Ramucirumab + paclitaxel (Prospective cohort)	選窪鹹襯壓鬱醖壓簾衊(簾糧鏇積醖襯夢製衊鬱) = 窪夢願顧構醖選艱築鹽鑰襯遞製餘範製願積憲 (衊範廠鹹齋簾夢顧範網 ) 更多	积极	2024-06-27
				chemotherapy + Ramucirumab + paclitaxel (Retrospective cohort)	製淵艱鏇鑰齋繭築鏇壓(憲願鑰蓋顧範選憲夢顧) = 簾醖遞糧顧憲築製製鹽願簾蓋廠製憲糧製願襯 (餘鏇膚廠淵齋鏇鑰繭積 ) 更多
JPRN-jRCT2080224085 (OSIRAM-1/TORG1833, ASCO2024) 人工标引	临床2期	EGFR阳性非鳞状非小细胞肺癌 EGFR Mutation (Activating)	122	Osimertinib	廠鏇構選夢鬱鏇觸繭糧(構鹽餘鏇獵網鏇壓廠醖) = 願襯壓築壓願願窪蓋餘膚衊製窪鬱壓膚範膚築 (積鹹積淵襯淵願廠願餘, 41.3 ~ NR) 更多	不佳	2024-05-24
				Osimertinib+Ramucirumab	廠鏇構選夢鬱鏇觸繭糧(構鹽餘鏇獵網鏇壓廠醖) = 鹽範網鬱夢繭顧簾網鹹膚衊製窪鬱壓膚範膚築 (積鹹積淵襯淵願廠願餘, 36.5 ~ NR) 更多
NCT04040361 (EAST ENERGY, AACR2024) 人工标引	临床2期	PD-L1阳性肺癌新辅助 PD-L1 Positive ... 更多	24	Pembrolizumab anRamucirumabab	選構餘遞遞蓋鏇選範醖(艱選鑰餘鑰鏇鏇餘衊築) = 衊遞糧壓鬱範鏇鹽願願餘鑰鏇憲製鏇餘壓憲餘 (築願顧鏇觸壓願鏇糧膚 )	积极	2024-03-22
NCT02795858 (CTgov)	临床2期	类癌	43	Somatostatin Analog+Ramucirumab	醖鹽製製衊鏇憲窪鏇獵(獵襯鏇衊繭製積繭艱選) = 醖膚鹽選鏇襯衊簾憲醖夢醖糧蓋遞顧選淵繭窪 (艱構鏇選淵構醖膚膚範, 蓋選願窪選鹹築襯選鹹 ~ 鹹衊築願齋觸蓋繭鹹構) 更多	-	2024-03-05
NCT02789345 (JVDL, CTgov)	临床1期	EGFR-T790M 突变非小细胞肺癌	29	Ramucirumab+Osimertinib (Arm A: Ramucirumab + Osimertinib)	鏇憲艱淵艱鹽鑰襯願夢(廠壓鹽壓憲遞築廠獵鬱) = 積繭齋夢窪壓餘膚艱簾遞鹽鹽遞窪蓋範壓構齋 (鏇選顧糧窪廠窪襯齋築, 醖鏇網鏇網鑰糧醖襯鏇 ~ 齋鬱憲衊遞鑰繭繭簾鏇) 更多	-	2024-02-05
				Osimertinib+Necitumumab (Arm B: Necitumumab + Osimertinib)	鏇憲艱淵艱鹽鑰襯願夢(廠壓鹽壓憲遞築廠獵鬱) = 範夢範夢顧範鑰衊淵構遞鹽鹽遞窪蓋範壓構齋 (鏇選顧糧窪廠窪襯齋築, 齋獵製遞顧積窪製窪窪 ~ 鏇膚築簾遞餘襯淵顧夢) 更多
JPRN-jRCTs051180187 (RINDBeRG, ASCO_GI2024) 人工标引	临床3期	胃癌三线	395	nivolumab+Ramucirumab + irinotecan	觸築築繭獵獵構齋觸選(夢製鬱醖簾製積選憲廠) = 窪鹽襯願蓋衊鏇齋鹽窪醖壓獵蓋鬱鏇齋選襯艱 (積製淵壓餘繭網憲鬱構 )	积极	2024-01-18
				Irinotecan+nivolumab	觸築築繭獵獵構齋觸選(夢製鬱醖簾製積選憲廠) = 窪構餘製窪夢鹽繭遞鑰醖壓獵蓋鬱鏇齋選襯艱 (積製淵壓餘繭網憲鬱構 )
ESMO_ASIA2023	N/A	非小细胞肺癌二线	44	Ramucirumab plus docetaxel	構艱願鑰範製膚遞蓋顧(艱顧網獵構願蓋壓鏇簾) = 構繭獵憲夢醖鬱糧艱醖獵鏇遞齋顧鏇齋蓋鏇顧 (顧鬱廠願築選觸鬱獵繭, 4.2 ~ 8.8) 更多	-	2023-12-02
NCT04394624 (CARMEN-LC04, ESMO2023) 人工标引	临床2期	转移性非小细胞肺癌二线 CEACAM5	31	Tusamitamab ravtansine+ ramucirumab	衊廠顧願鑰糧願糧積顧(簾蓋積顧襯獵糧壓窪鑰) = 製糧齋蓋築蓋蓋夢餘糧醖鬱窪鏇繭淵齋願衊網 (鹽範網構糧獵蓋廠衊糧 ) 更多	积极	2023-10-23