A Phase I Study of Zanzalintinib With Pembrolizumab and Cetuximab in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

This Phase I clinical trial evaluates the safety, tolerability, and optimal dosing of Zanzalintinib in combination with Pembrolizumab and Cetuximab in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC). The study aims to establish the maximally tolerated dose (MTD) and recommended Phase II dose (RP2D) while also exploring efficacy outcomes, including progression-free survival (PFS) and overall survival (OS).

开始日期2025-06-05

申办/合作机构

The University of Chicago

[+1]

NCT06959589

/ Not yet recruiting临床2期IIT

An Open-label, Multicenter, Single-arm Phase II Clinical Study Evaluating the Efficacy and Safety of IBI351, Cetuximab β Combined With FOLFIRI as First-line /IBI351, Cetuximab β as Second-line in the Treatment of KRAS G12C-mutated Metastatic Colorectal Cancer

This is an open-label, multicenter, single-arm Phase II clinical study, divided into subgroups A and B:
Cohort A - To evaluate the efficacy and safety of IBI351, cetuximab β combined with FOLFIRI as first-line treatment for metastatic colorectal cancer with KRAS G12C mutations; Twenty untreated patients with advanced colorectal cancer with KRAS G12C mutation are proposed to be enrolled and treated with the first-line IBI351+ cetuximab β injection +FOLFIRI regimen. The historical reference is expected to be around 40-50%, and it is expected to increase to around 75%. Therefore, among the 20 patients, if ≥15 patients achieve remission, it is considered that the efficacy of the trial protocol is statistically significant.
Cohort B - To evaluate the efficacy and safety of BI351 and cetuximab β as second-line treatment for metastatic colorectal cancer with KRAS G12C mutations.
It is proposed to enrolled 30 patients with advanced colorectal cancer with KRAS G12C mutation who have progressed after first-line treatment, and evaluate IBI351+ cetuximab β injection for second-line treatment. The historical reference is around 25%, and it is expected to increase to around 50%. Therefore, among the 30 patients, if ≥15 patients achieve remission, it is considered that the efficacy of the trial protocol is statistically significant.
Imaging assessment of tumor remission was conducted every 8 weeks until disease progression. The period from the start of treatment to disease progression is defined as PFS. The safety observation indicators include: the incidence and severity of adverse events (AE) and serious adverse events (SAE); Laboratory tests, vital signs, physical examinations, and changes in electrocardiogram (ECG). Record the subsequent tumor treatment and survival follow-up after the progression.
Definition of study conclusion: The study will conclude after the last subject has been treated for 2 years or has completed the treatment (whichever occurs first).

开始日期2025-06-01

申办/合作机构

浙江大学医学院附属第二医院（浙江省第二医院）

NCT06959693

/ Not yet recruiting临床2/3期IIT

mFOLFOX and Cetuximab - β With or Without Envafolimab for MSS, RAS/BRAF Wild - Type Advanced Unresectable CRC: Prospective, Randomized, Controlled Phase Ⅱ/Ⅲ Trial

This is a prospective randomized controlled Phase Ⅱ/Ⅲ Clinical study to evaluate the clinical efficacy and safety of Envafolimab combining with Cetuximab -β and mFOLFOX6 in Patients With MSS, RAS/BRAF Wild-Type Metastatic Colorectal Cancer (mCRC)

开始日期2025-06-01

申办/合作机构

中山大学

100 项与西妥昔单抗相关的临床结果

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100 项与西妥昔单抗相关的转化医学

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100 项与西妥昔单抗相关的专利（医药）

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8,272

项与西妥昔单抗相关的文献（医药）

2025-12-01·Journal of Gastrointestinal Cancer

Anti-EGFR Rechallenge in Metastatic Colorectal Cancer and the Role of ctDNA: A Systematic Review and Meta-analysis

Review

作者: da Silva, Luís Felipe Leite ; Peixoto, Renata D 'Alpino ; Saldanha, Erick Figueiredo ; da Conceição, Lucas Diniz ; Noronha, Mariana Macambira ; da Silva, Marcos Vinícius Martins Grangeiro

BACKGROUND:

Metastatic colorectal cancer (mCRC) remains a significant clinical challenge. While anti-EGFR inhibitors have improved survival rates, their long-term efficacy is limited by disease progression, which is often associated with the development of acquired resistance mutations. However, some patients may regain sensitivity to anti-EGFR agents after alternative therapies, suggesting a potential benefit for rechallenge strategies. Our study aims to conduct a systematic review and meta-analysis to comprehensively evaluate the efficacy and safety of EGFR rechallenge in patients with mCRC.

METHODS:

A systematic search of the MEDLINE, EMBASE, and Cochrane databases was conducted between October 28 and December 24, 2023, to identify clinical trials investigating treatment regimens incorporating panitumumab or cetuximab as a rechallenge strategy. Pooled proportions or hazard ratios (HR) were calculated using a random effects model. Inter-study heterogeneity was assessed using the I².

RESULTS:

Among the 2105 articles identified through the search, 13 met the predetermined inclusion criteria. Of these, 12 were phase II studies, encompassing 92.3% of the patient population. Cetuximab was administered to 302 patients (75.1%), whereas panitumumab was utilized in 100 patients (24.9%).A pooled analysis of eight studies demonstrated an objective response rate of 20.50% (95% CI 7.94 to 33.07) and a disease control rate of 67.35% (95% CI 58.60 to 76.09). The median progression-free survival was estimated at 3.5 months (95% CI 2.68-6.69), with a median OS of 9.8 months (95% CI 6.71-12.89). Patients exhibiting RAS wild-type status in circulating tumor DNA (ctDNA) analysis derived enhanced benefits from anti-EGFR rechallenge (HR: 0.41; 95% CI 0.28-0.60, I² = 60%). Common grade 3 or higher treatment-related adverse events included neutropenia (22.8%) and rash (14.9%).

CONCLUSION:

This meta-analysis underscores the efficacy and safety of anti-EGFR rechallenge as a promising therapeutic approach for a subset of patients afflicted with mCRC. The observed correlation between wild-type RAS status, as determined through ctDNA analysis, and improved OS signals the prospect of precision oncology in guiding treatment decisions.

2025-12-01·Journal of Gastrointestinal Cancer

Efficacy and Safety of Anti-EGFR Therapy Rechallenge in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis

Review

作者: Burbano, Rommel Mario Rodríguez ; de Oliveira Rodrigues, Anna Luíza Soares ; de Moraes, Francisco Cezar Aquino ; Limachi-Choque, Jhonny ; Priantti, Jonathan N

BACKGROUND:

Colorectal cancer (CRC) represents the second leading cause of cancer-related mortality worldwide, with a significant portion of patients presenting with metastatic disease at diagnosis. Resistance to initial anti-EGFR therapy, a key treatment for RAS wild-type metastatic CRC, remains a major challenge. This study aimed to assess the efficacy and safety of rechallenge with anti-EGFR therapy in patients with metastatic CRC who have progressed after prior treatments.

METHODS:

A systematic search was conducted across PubMed, Web of Science, Cochrane, and Scopus. Studies were included if they were randomized controlled trials (RCTs) or observational studies involving patients with EGFR-mutated metastatic CRC who received anti-EGFR therapy as a rechallenge. Endpoints included objective response rate (ORR), disease control rate (DCR), and the incidence of adverse events. Statistical analyses were performed using the DerSimonian/Laird random effect model, with heterogeneity assessed via I² statistics. R, version 4.2.3, was used for statistical analyses.

RESULTS:

Fourteen studies were included with 520 patients; 50.3% were male, and the median age was 63 years old. The median progression-free survival (mPFS) ranged between 2.4 and 4.9 months, while the median overall survival (mOS) ranged from 5 to 17.8 months. Our pooled analysis demonstrated an objective response rate (ORR) of 17.70% (95% CI, 8.58-26.82%) and a disease control rate (DCR) of 61.72% (95% CI, 53.32-70.11%), both with significant heterogeneity (I², 84% and 80%, respectively; p < 0.01). In the subgroup analysis, cetuximab showed an ORR of 18.31% (95% CI, 4.67-31.94%), and panitumumab an ORR of 10.9% (95% CI, 0.00-26.82%), while the combination of both resulted in an ORR of 29.24% (95% CI, 0.00-65.84%). For DCR, cetuximab resulted in 62.1% (95% CI, 49.32-74.87%), panitumumab in 63.05% (95% CI, 52.13-73.97%), and the combination in 60.34% (95% CI, 31.92-88.77%), all with significant heterogeneity. Adverse events included anemia (15.39%), diarrhea (4.20%), hypomagnesemia (6.40%), neutropenia (22.57%), and skin rash (13.22%).

CONCLUSIONS:

Rechallenge with anti-EGFR therapy in metastatic CRC patients shows moderate efficacy with manageable safety profiles. These findings highlight the need for careful patient selection and monitoring to optimize outcomes. Further studies are warranted to refine strategies for maximizing the therapeutic benefits of anti-EGFR rechallenge.

2025-07-01·CANCER LETTERS

Phase 3 randomized study of physician choice vs metronomic chemotherapy in platinum refractory/ineligible head and neck cancer in palliative setting with survival outcomes

Article

作者: Khatwani, Itesh ; Modi, Gaurang ; Pathak, Anand ; Wilson, Lovin ; Thavarool, Sajith Babu ; Karpe, Ashay ; Gupta, Tara Chand ; Rajamanickam, Deepan ; Turkar, Siddharth ; Shenoy Vp, Praveen Kumar ; Singh, Gunjesh ; Jadhav, Monica ; Prabhash, Kumar ; Mandal, Tanmoy Kumar ; Bhosale, Bharat ; Jha, Bhavya ; Pande, Nikhil ; Poladia, Bhavesh ; Katna, Rakesh ; Talreja, Vikas T ; Chandrasekharan, Arun ; Bhagyavant, Priyanka ; Rajamanickam, Saravana ; Avaronnan, Manuprasad ; Das, Sudeep ; Muley, Sonal ; Singh, Unnati ; Sonwani, Vaibhav ; Madankar, Kamlesh ; Raut, Nirmal ; Peelay, Zoya ; Kolkur, Manali ; Patil, Vijay ; Alone, Mitali ; Noronha, Vanita ; Pathak, Shruti ; Sen, Nibedita ; Kothari, Rushabh ; Singh, Ravikant ; Kumar, Gautam ; Banavali, S D ; Bhatt, Palak ; Madala, Ravi Krishna ; Shrirangwar, Sameer

There are multiple options of treatment in second line therapy for locally advanced head and neck squamous cell carcinoma (LAHNSCC) treated with palliative intent. However, triple metronomic chemotherapy is oral, cost-effective, and resource-efficient. Hence this phase 3 randomized trial compares National Comprehensive Cancer Network (NCCN) recommended physician choice therapy versus triple metronomic chemotherapy (TMC) in the second-line treatment of head and neck cancer This study, designed to establish superiority, was conducted in India across 16 sites under the Cancer Research Statistics Foundation. The study recruited 114 LAHNSCC who were treated with palliative intent in second line. These patients underwent 1:1 central stratified randomization to either triple metronomic chemotherapy or physician choice therapy (taxane, 5fu/capecitabine, afatinib, nivolumab/pembrolizumab, cetuximab).At a median follow-up of 258 (95 % CI 209-306) days, the median overall survival of the triple metronomic chemotherapy was 181 days (95 %CI 142.7-219.2) versus 123 days (95 %CI 94-152) in the physician choice therapy arm (P = 0.00.002). The median progression free survival was 120 days (95 %CI 89.2-150.8) versus 70 days (95 % CI 58.2-81.8) in metronomic chemotherapy and in the physician choice therapy arms respectively (P < 0.001).These results suggest that TMC significantly improves survival outcomes over physician choice therapy in platinum-refractory head and neck cancer.

1,014

项与西妥昔单抗相关的新闻（医药）

2025-05-06

·求实药社

大涨45.6%！LAG3抗体联合K药一线治疗头颈癌较K药单药历史OS数据翻倍！达17.6个月~

来源：新猎药人笔记2025年5月5日——Immutep公司宣布，其TACTI-003试验的B队列中，Eftilagimod Alfa（efti）联合Pembrolizumab（商品名：KEYTRUDA®）作为一线治疗方案，在PD-L1表达水平低于1（CPS<1）的复发性/转移性头颈鳞状细胞癌（HNSCC）患者中，取得了17.6个月的成熟中位总生存期（OS）。TACTI-003试验是一项IIb期研究，旨在评估Eftilagimod Alfa与Pembrolizumab联合治疗的安全性和有效性。此次公布的B队列数据截至2025年3月31日，共有31名可评估患者。此前，该联合疗法已在多个临床试验中显示出良好的响应率和耐受性。这一结果显著优于历史数据中单独使用抗PD-1单药治疗的7.9个月中位总生存期，以及化疗联合抗PD-1治疗的11.3个月和化疗联合西妥昔单抗治疗的10.7个月。此外，该无化疗联合疗法耐受性良好，未出现新的安全性信号，并且在治疗过程中实现了多次完全缓解。受此消息影响，Immutep公司股价大涨45.6%！Immutep首席执行官Marc Voigt表示：“我们很高兴看到这种联合疗法在PD-L1低表达的‘冷肿瘤’患者中取得了如此显著的生存益处。这种联合疗法将两种互补的免疫疗法相结合，使响应率提高了7倍，中位总生存期比抗PD-1单药治疗的历史结果翻了一番。”他还指出，这种联合疗法对于那些缺乏免疫疗法选择的患者群体具有重要意义。鉴于Eftilagimod Alfa在HNSCC治疗中的快速通道资格，Immutep已请求与美国食品药品监督管理局（FDA）会面，讨论下一步的监管步骤和潜在的批准路径。公司计划在年内提供进一步的数据更新。Eftilagimod Alfa是Immutep开发的一种可溶性LAG-3蛋白和MHC II类激动剂，通过激活抗原呈递细胞（APC）来增强先天和适应性免疫反应。该药物目前正在进行多项临床试验，包括非小细胞肺癌（NSCLC）、头颈鳞状细胞癌（HNSCC）和转移性乳腺癌等实体瘤的治疗。结束语：免疫检查点最近几年发现不是特别的顺利，除了BMS的LAG3和O药联用获批用于黑色素瘤之外，没有其他的免疫检查点有更多进展，明星靶点TIGIT相继折戟。此次，IMMUTEP的LAG3融合蛋白联合K药显著显著提高头颈癌总生存期，数据着实惊艳！估计今天上班就有很多药企开始翻箱底找还有没有LAG3的资产了。免责声明：文章内容仅供参考，不构成投资建议。投资者据此操作，风险自担, 关于对文中陈述、观点判断保持中立，不对所包含内容的准确性、可靠性或完整性提供任何明示或暗示的保证。请读者仅作参考，并请自行承担全部。联系我们I-RNA 2025展位火热预定中！扫码立即咨询电话：13816031174（同微信）赞助形式包括但不仅限于演讲席位、会场展位、会刊彩页、晚宴赞助、会议用品宣传等。点击此处“阅读全文”咨询更多！

免疫疗法临床2期临床结果

2025-05-05

·FierceBiotech

Immutep takes immunotherapy a step further with \'impressive\' survival data from Keytruda combo

Eftilagimod and Keytruda\'s median overall survival data in first-line, PD-L1-negative head and neck cancer look favorable to historical data on a cross-trial comparison basis. \n Immutep believes its LAG-3 candidate eftilagimod alpha may have a path to approval in first-line head and neck cancer after reporting what one analyst deems “impressive” overall survival data.Monday, Immutep said a combination of eftilagimod and Merck & Co.’s Keytruda helped patients live a median of 17.6 months when used as first-line therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with PD-L1 expression below a combined positive score (CPS) of 1.The overall survival result came from 31 evaluable patients enrolled in cohort B of a phase 2b trial coded Keynote-C34, or Tacti-003. The trial doesn’t have an active internal control arm. But as Immutep noted, the 17.6-month median looks better than historical data from two existing standard-of-care regimens. In a note, Jefferies analyst David Stanton, M.D., called the survival readout “impressive.”Immutep suggests that a high unmet need for first-line treatment of PD-L1-negative HNSCC could potentially pave eftilagimod a path to approval, and the Australian biotech has requested a meeting with the FDA to discuss that. Eftilagimod already boasts an FDA “fast track” designation in first-line HNSCC.“Given the strength of the efficacy and safety results generated to date with efti in combination with [Keytruda], we will meet with regulators to discuss next steps and potential paths to approval,” Immutep CEO Marc Voigt said in a statement.According to Voigt, the eftilagimod-Keytruda combo’s value proposition lies in that it offers a potential immunotherapy-only regimen, while the standards today for PD-L1-negative patients all include chemotherapy. Eftilagimod is a LAG-3 fusion protein, which activates antigen-presenting cells to boost an immune response, according to Immutep. Back in 2019, the FDA approved Keytruda in combination with chemotherapy for all patients with first-line HNSCC, including those with PD-L1-negative tumors. The approval was based on the phase 3 Keynote-048 trial showing that Keytruda plus chemo reduced the risk of death by 23% versus Eli Lilly’s EGFR inhibitor Erbitux and chemo in the overall population regardless of PD-L1 expression levels. At the time, the FDA simultaneously approved Keytruda monotherapy but only for PD-L1-positive tumors that express the biomarker at CPS score at or above 1.A post hoc analysis of Keynote-048 later showed that Keytruda-chemo didn’t demonstrate a clear overall survival benefit over Erbitux-chemo in the PD-L1-negative subgroup. The median overall survival was 11.3 months versus 10.7 months. The death risk was even 21% higher for that subgroup for the Keytruda-chemo arm, although researchers cautioned that this analysis was only descriptive and limited by the small number of patients involved.Regardless of Keytruda-chemo’s position, eftilagimod and Keytruda’s 17.6-month median overall survival length now looks better than those by the two chemo-containing regimens with the obvious caveat of a cross-trial comparison.The latest overall survival showing builds on some promising tumor response data from the Immutep regimen. Last year, Immutep reported a 35.5% objective response rate—including 12.9% complete responses—for eftilagimod and Keytruda from cohort B of Tacti-003. The numbers compare favorably to Keytruda-chemo’s 30.8% ORR—including 2.6% CR—in Keynote-048’s PD-L1-negative subgroup.“Driving durable responses that translate into clinically meaningful survival holds tremendous promise for these patients in need of more tolerable and efficacious therapies,” Voigt said in a statement Monday. Immutep looks poised to carve out a niche market from PD-L1-negative disease, which makes up about 20% of first-line HNSCC patients, according to the company. As Voigt noted, there’s a lack of competitor chemo-free trials targeting this population.Merck recently partnered with Exelixis to combine Keytruda with the latter company’s investigational tyrosine kinase inhibitor zanzalintinib in HNSCC. However, the pair’s phase 3 Stellar-305 trial is only testing that combo in PD-L1-positive patients.Similarly, Merus, with an FDA “breakthrough therapy” designation, is evaluating its EGFRxLGR5 bispecific antibody petosemtamab with Keytruda in first-line HNSCC in the phase 3 LiGeR-HN1 trial—again only in PD-L1-positive patients.

$Immutep takes immunotherapy a step further with \'impressive\' survival data from Keytruda combo$

临床3期临床结果快速通道临床2期免疫疗法

2025-05-05

·深蓝观

2025AACR一览：MNC沉寂，中国ADC开启“新靶点2.0”

李昀 | 撰文又一 | 编辑上周（4月30日），为期六天的AACR（美国癌症研究协会）年会在芝加哥闭幕。作为领域内最重要的展示平台和交流机会，来自中国的参会者给出了足够高的关注。“每年AACR来自中国的参会者都越来越多，但今年和去年相比，感觉是爆发式的增长。亚洲面孔充斥了各种场合，尤其是一些我们擅长的领域，比如ADC。”一名参会多年的行业人士说到。根据统计，这次来参会的中国药企有111家，设计创新药246款；其中ADC就有86款，占比35%。其中不少公司，已经在今年的JPM上有过亮相。但AACR和JPM、ASCO的侧重点略有不同，因此参会目的也不同。“在JPM上，投资者是主角。公司的团队也是希望能拿到合作和资金。而AACR和ASCO则更偏向科研：其中AACR上来自公司的研发人员比较多，而ASCO来的临床医生会比较多。”“所以和JPM相比，AACR的会间谈话都是有点nerd的。”上述人士调侃道，“氛围上有细微的差别。在JPM上大家身上多少带着些任务，但是来AACR就感觉就是纯粹来上学的，聊天的都是同学。”随着今年国内资本环境没有明显转好，而出海的口子却越扩越大，因此，在学术展示和交流之外，参会企业也会尤其留心两类信息：一是MNC都在干什么；二是公司核心管线的竞品数据。“有些公司会选择在JPM上接触MNC。但在JPM上，MNC展示的一般都是比较成熟的管线；而在AACR上，你能看到这些MNC又有什么新方向。可能数据的不确定性还很高，但这正是可以合作的地方。”一名在美工作的BD说到。-01-来自MNC的消息由于AACR是很多新药和新疗法首次亮相的舞台，因此展出内容以早中期临床分析为主。其中不少展现出令人惊艳的潜力，但由于距离成功还有一段距离，因此外界关注度一般。但不可否认的是，它们提示了未来行业的可能性。比如来自勃林格殷格翰的HER2突变NSCLC新药 Zongertinib，在这次大会上就受到了很大关注。这是一种TKI类药物，最新公布的三期临床数据极其乐观：ORR高达71%，为该亚型癌症中前所未有的高水平。要知道，上一个同适应症新药Enhertu在去年的全球销售额达到了37.54亿美元。这说明虽然针对HER2这一靶点的研究已经不算新鲜，但其可能带来的商业价值还远远未饱和。而Enhertu的ORR为50%左右，仅这一点而言Zongertinib就表现出很大的潜能。同时，Zongertinib 的给药方式为口服，和注射的Enhertu相比依从性更好。“单就这一个适应症而言，Zongertinib未来成为标准疗法的可能性很大。但是技术手段不同，TKI对突变位点的要求更高，所以不太适合跨癌种。”另一款引发重点讨论的新药是来自GSK的Jemperli。年会上，GSK主要展示了这款PD-1单抗的最新治疗数据：在治疗103名dMMR/MSI-H局部晚期直肠癌患者时，84名出现临床完全缓解，即没有癌症迹象，而其中82名患者未接受手术。这项研究之所以重要，是因为它给予了一种可能性：未来的癌症治疗，患者不需要手术、化疗或放疗，可以实现器官保留。纽约纪念斯隆凯特琳癌症中心的研究负责人也对这项研究高度评价：如果在更大规模的试验中证实这一结果，单独使用免疫疗法是完全可能实现的。因此，尽管dMMR/MSI-H局部晚期直肠癌属于小适应症，但它提示了免疫治疗在“完全治愈”和“替代入侵式治疗”上存在很大发展空间，或许会颠覆目前局部癌症的治疗模式。K药也带来了一些新鲜的适应症。比如Keynote-689这项针对局部晚期头颈部鳞状细胞癌的临床，将患者的复发或死亡风险降低了27%。虽然和其它适应症相比，K药这次数据表现比较一般，但这是该癌种“在二十多年来的首个阳性实验”，因此对患者而言具有里程碑的意义。该适应症的上市申请正在接受FDA 优先审查，将于6月得到答复。可以看到，在这次的AACR上，曝光度比较高的还是一些老药和老靶点。也因此，不少参会者认为今年是“小年”。“今年大药企很多都是公布随访数据，没有什么FIC的新动作。之后在ASCO上会有更加详细的数据释出，目的还是为临床推广做准备。”上述参会人员说到。-02-KRAS受到关注在今年AACR上，对于KRAS这一靶点来说足以称得上是大年了。在过去几年的重要行业年会上，KRAS的风头一直被TROP2、CLDN18.2等热门靶点盖过，直到今年多个KRAS G12D抑制剂首次公布临床前或临床I期数据，并表现出优异效果，引起了各方兴趣。“KRAS G12C曾经火过一阵子，但效果相对其它治疗方式，确实没有太突出的地方。现在轮到G12D了，相对于G12C来说，它适合的胰腺癌没有太多靶向药物，所以突破的意义更大。”上述参会人员解释道。劲方医药和Verastem联合开发的VS-7375公布了一项临床前数据，显示其在治疗KRAS G12D突变的胰腺癌患者上有一定发现。研究显示，VS-7375能同时作用于KRAS 蛋白的 “开启”和“关闭”状态，这意味着无论该蛋白是否促进细胞增殖，它都能发挥作用。目前，劲方已在国内开展该药的II期临床试验，而Verastem则预计于年中开启I/IIa期试验。来自Revolution的Zoldonrasib拿出了Ⅰ期结果：在 90 例KRAS G12D突变的晚期实体瘤患者中，对其中18 例可评估疗效的非小细胞肺癌患者进行分析，ORR为 61%，DCR为89%，中位缓解时间为1.4 个月，这表明药物起效相对较快，且与传统标准治疗多西他赛相比有显著提高。除了KRAS G12D以外，已有药品上市的KRAS G12C药物也在曾经困扰过的问题上有了一些突破。来自安进的Sotorasib和来自Mirati的Adagrasib都属于已经上市的KRAS G12C药物，用以治疗相关突变NSCLC，在耐药性上被市场验证为较差。而在此次AACR大会上，一些新思路提供了解决方向：比如Genprex公司的研究展示了通过基因疗法克服Sotorasib获得性耐药问题等。同时，之前KRAS G12C主要用于NSCLC的治疗，而此次AACR上的报告显示：其与EGFR 抗体Sotorasib + 帕尼单抗，Adagrasib + 西妥昔单抗）的联合治疗对结直肠癌也很有效果。两家公司都在今年对临床的最新进展做了汇报。除了上述提到的几款药物，还有礼来的LY4066434、阿斯利康的AZD0240带来了相关内容的展示。由于阶段尚早，展示内容主要集中在抗肿瘤活性上。但这两家公司切入KRAS的方式比较特别：礼来做的是泛KRAS抑制剂，旨在应对多种突变；阿斯利康做的则是TCR-T疗法。那么，这一次的KRAS热是否会是昙花一现？上述BD人士认为，这股热潮能否持续下去，还要看后续的证据支持。“接下来的ASCO上，大概率会有更多相关的数据展出。但这个领域的探索比较少，临床风险比较高，所以不太可能出现一窝蜂内卷的情况。”-03-ADC的天下和之前几届一样，这一届AACR的ADC展示，依然被中国药企承包了。而一些ADC新靶点的展示，也为这次有些沉寂的大会带来了一些变化。其中讨论度最高的就是CDH17。这一靶点虽然具有很多理想特性：比如组织特异性，但它在部分正常组织中仍有可检测水平。以前，当ADC的连接子还不够稳定时，这种研发风险较高的靶点常常被视为边缘。而如今随着ADC技术的提升，对这一新靶点的尝试也越来越多。今年的AACR上，做出相关报告的中国企业就不胜枚举：包括维立志博的LBL-054、华东医药的HDM2017、宜联生物的YL127、SOTIO Biotech的SOT109、博奥信生物的BSI-721、橙帆医药的VBC108、礼新医药的LM-350、先声药业的SCR-A008等。同样第一个开始吃螃蟹的还有基石药业的CS5006，这是同类首创、靶向全新靶点ITGB4 的ADC，目标适应症包括NSCLC、头颈鳞状细胞癌、食管鳞状细胞癌等。AACR上展示的临床前研究显示，CS5006在多种动物模型中均表现出强效的抑瘤作用，且耐受性良好。除了新靶点以外，不少公司在技术手段上也多有探索。比如康弘药业的KH815，就是全球首款进入临床阶段的双毒素 ADC 新药。它搭载了拓扑异构酶1 抑制剂和 RNA 聚合酶 II 抑制剂两种有效载荷，可以通过协同作用进行多维打击，从而克服传统单毒素 ADC 存在的耐药现象。再比如宜联生物开发的非内吞ADC，通过肿瘤微环境特异性酶来释放毒素，进一步打开了 ADC 药物的应用空间。尽管上述创新度较高的管线目前还处于临床前或临床早期，但它们的大部分都被高盛选为今年大会上最值得关注的中国资产。由此可以看出不仅是MNC，国外资本同样意识到了国内早期开发工作的价值所在。“这次ADC展出给我的总体感觉是，国内企业的胆子确实越来越大了。”上述BD人士由于长期不在国内，同时也不是ADC领域从业者，因此对这次的全新印象感到有些惊讶。“这说明很大情况下，‘内卷’是信心不足的结果。在积累了那么多出海的成功案例之后，感觉国内越来越放开手脚了。”就在一个月后，同样在芝加哥，另一场行业盛会ASCO也将举行。尽管大环境的向好变化很难体察，但可以肯定的是：这些公司不会停下他们前往的脚步。......欢迎添加作者交流：李昀：liyun940820

AACR会议临床结果抗体药物偶联物ASCO会议

100 项与西妥昔单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D03455	西妥昔单抗	L01XC06	DB00002

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
RAS 野生型结直肠癌	澳大利亚	Merck Healthcare Pty Ltd.	2007-09-25
头颈部肿瘤	美国	Eli Lilly & Co.	2006-03-01
转移性结直肠癌	欧盟	Merck Europe BV	2004-06-29
转移性结直肠癌	冰岛	Merck Europe BV	2004-06-29
转移性结直肠癌	列支敦士登	Merck Europe BV	2004-06-29
转移性结直肠癌	挪威	Merck Europe BV	2004-06-29
头颈部鳞状细胞癌	欧盟	Merck Europe BV	2004-06-29
头颈部鳞状细胞癌	冰岛	Merck Europe BV	2004-06-29
头颈部鳞状细胞癌	列支敦士登	Merck Europe BV	2004-06-29
头颈部鳞状细胞癌	挪威	Merck Europe BV	2004-06-29
结直肠癌	瑞士	Merck & Co., Inc.	2003-12-01

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
KRAS G12C突变结直肠癌	临床3期	美国	Mirati Therapeutics, Inc.	2021-06-24
KRAS G12C突变结直肠癌	临床3期	中国	Mirati Therapeutics, Inc.	2021-06-24
KRAS G12C突变结直肠癌	临床3期	阿根廷	Mirati Therapeutics, Inc.	2021-06-24
KRAS G12C突变结直肠癌	临床3期	澳大利亚	Mirati Therapeutics, Inc.	2021-06-24
KRAS G12C突变结直肠癌	临床3期	奥地利	Mirati Therapeutics, Inc.	2021-06-24
KRAS G12C突变结直肠癌	临床3期	比利时	Mirati Therapeutics, Inc.	2021-06-24
KRAS G12C突变结直肠癌	临床3期	巴西	Mirati Therapeutics, Inc.	2021-06-24
KRAS G12C突变结直肠癌	临床3期	加拿大	Mirati Therapeutics, Inc.	2021-06-24
KRAS G12C突变结直肠癌	临床3期	哥伦比亚	Mirati Therapeutics, Inc.	2021-06-24
KRAS G12C突变结直肠癌	临床3期	捷克	Mirati Therapeutics, Inc.	2021-06-24

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临床结果

适应症

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


NCT04853043 (APK Mutant, CTgov)	临床2期	转移性结直肠癌	7	Cetuximab	網獵鏇鹹獵廠壓衊餘願(鹹網築遞範範選願選憲) = 鹹繭構範網憲艱憲鹹淵憲繭糧糧衊鏇鑰積鹽遞 (蓋醖鏇醖鹹淵製繭網淵, 構範餘遞憲壓憲願選範 ~ 顧製鏇衊醖觸夢憲構膚) 更多	-	2025-05-06
NCT00545545 (CTgov)	临床1/2期	复发性结直肠癌 \| 结直肠癌	32	PGG+Cetuximab+Irinotecan (Arm 1, Imprime PGG Injection 2 mg/kg+ Cetuximab + Irinotecan)	夢簾憲廠築醖構網簾齋 = 鏇繭繭糧網繭淵鏇鑰醖壓壓範鬱衊繭鏇鬱襯齋 (衊網餘齋積夢選鹽齋獵, 蓋餘餘鹹淵網糧獵繭齋 ~ 築糧窪糧壓構衊衊衊顧) 更多	-	2025-03-19
				PGG+Cetuximab+Irinotecan (Arm 1, Imprime PGG Injection 4 mg/kg+ Cetuximab + Irinotecan)	夢簾憲廠築醖構網簾齋 = 遞範繭淵繭選網願範糧壓壓範鬱衊繭鏇鬱襯齋 (衊網餘齋積夢選鹽齋獵, 獵餘鹹鑰醖構衊製鏇齋 ~ 簾顧憲齋蓋醖製鹽壓構) 更多
JPRN-jRCTs061180022 \| NCT02515734 (JACCRO CC-13, ASCO_GI2025) 人工标引	临床2期	RAS 野生型结直肠癌 RAS wild-type	359	m-FOLFOXIRI plus cetuximab	蓋襯艱廠衊衊淵鹹齋觸(齋淵壓遞簾窪醖淵範糧) = 鑰選膚簾繭憲選顧網壓鬱範夢醖觸積繭範鏇繭 (獵夢窪範積獵夢鏇廠糧 ) 更多	积极	2025-01-23
				m-FOLFOXIRI plus bevacizumab	蓋襯艱廠衊衊淵鹹齋觸(齋淵壓遞簾窪醖淵範糧) = 積網鑰構餘選鏇憲觸醖鬱範夢醖觸積繭範鏇繭 (獵夢窪範積獵夢鏇廠糧 ) 更多
NCT04607421 (BREAKWATER, ASCO_GI2025 \| Pubmed \| FDA) 人工标引	临床3期	BRAF V600E突变结直肠癌一线 BRAF V600E	479	Encorafenib + Cetuximab + FOLFOX	衊鹹鏇範顧選鑰淵餘網(簾鑰夢構顧衊簾範積簾) = 積鏇糧餘艱夢鏇範鏇觸觸觸齋壓齋壓衊糧選顧 (獵夢遞窪鬱範積簾鬱窪, 51.6 ~ 69.5) 更多	积极	2025-01-23
				Standard of Care (chemo with or without bevacizumab)	衊鹹鏇範顧選鑰淵餘網(簾鑰夢構顧衊簾範積簾) = 醖壓艱襯簾觸觸獵顧範觸觸齋壓齋壓衊糧選顧 (獵夢遞窪鬱範積簾鬱窪, 31.3 ~ 49.3) 更多
NCT03785249 (KRYSTAL-1, ASCO_GI2025) 人工标引	临床1/2期	KRAS G12C突变结直肠癌二线 KRAS G12C	94	Adagrasib + Cetuximab	網蓋鑰鏇憲艱選構遞襯(顧襯衊糧憲鬱觸簾製廠) = 衊製醖艱願築淵艱鏇襯簾膚繭壓獵範醖夢築網 (鑰蓋觸衊膚壓壓齋觸蓋, 32 ~ 53) 更多	积极	2025-01-23
ASCO_GI2025	N/A	一线 RASwild-type	756	anti-epidermal growth factor receptor agents (Elderly patients (age ≥ 70 years))	築糧範膚壓顧餘鏇蓋襯(壓膚製選範範壓願醖襯) = Regarding hematologic SAEs, a significant higher incidence of grade ≥ 3 anemia was found in elderly patient group (13.3% vs 5.0%, p= 0.003) 觸簾壓膚淵網鬱廠遞淵 (膚繭築積廠築餘廠範醖 ) 更多	积极	2025-01-23
				anti-epidermal growth factor receptor agents (Patients < 70 years old)
NEW BEACON (ASCO_GI2025)	临床2期	BRAF V600E突变结直肠癌 BRAF V600E mutated	20	Cetuximab every second week + Encorafenib	淵網簾網蓋鹽鑰壓鏇齋(餘簾獵鏇膚顧憲鬱範憲) = 襯鑰選願構選醖鬱鬱鹹壓簾蓋襯簾鏇範壓壓衊 (淵膚艱繭餘遞鏇積壓築 )	积极	2025-01-23
NCT04241731 (ESMO_ASIA2024) 人工标引	临床2期	RAS 野生型结直肠癌维持 \| 一线 RAS wild-type	31	Cetuximab plus Raltitrexed	鏇獵選鏇齋鏇鬱範網鬱(淵夢壓淵夢襯糧選構夢) = 衊醖膚膚鑰遞蓋鹹糧積選壓糧獵網憲膚鹽餘廠 (糧網糧醖顧顧鏇糧觸願, 3.2 ~ 12.0) 更多	积极	2024-12-07
NCT03258554 (NRG-HN004, Pubmed \| Lancet Oncol) 人工标引	临床2/3期	头颈部肿瘤	186	Durvalumab	鹹築窪鹽觸鏇簾憲選願(鑰淵窪膚簾鏇蓋鏇壓鹽) = The most common grade 3-4 adverse events were dysphagia (26 [22%] of 119 patients in the durvalumab group vs 18 [30%] of 61 patients in the cetuximab group), lymphopenia (33 [28%] vs 20 [33%]), and oral mucositis (13 [11%] vs 11 [18%]). 鑰齋範願蓋夢網簾願襯 (網襯蓋願鏇鬱衊觸積壓 ) 更多	不佳	2024-12-01
				Cetuximab
SITC2024 人工标引	临床1期	结直肠癌 Proficient DNA Mismatch Repair (pMMR)	15	pre-A+E CBNK cells + cetuximab	壓範範範範築繭廠憲窪(艱簾鹹夢鹹淵獵蓋簾壓) = None 壓鑰壓範窪襯襯獵窪蓋 (鹹艱夢餘壓構醖艱鏇淵 ) 更多	积极	2024-11-05