Pegaspargase

2024年美国临床肿瘤学会（ASCO）年会上，由华中科技大学同济医学院附属协和医院张利玲教授团队开展的“卡瑞利珠单抗联合培门冬酶、依托泊苷和大剂量甲氨蝶呤治疗NK/T细胞淋巴瘤患者的II期前瞻性研究(CLAMP研究)”结果入选大会口头报告。北京时间6月2日，张利玲教授报告了该研究的最新数据。研究结果表明 1 ，卡瑞利珠单抗联合培门冬酶、依托泊苷和大剂量甲氨蝶呤治疗NK/T细胞淋巴瘤患者具有良好的疗效和安全性，有望成为此类患者新的治疗选择。 CLAMP研究入选2024 ASCO大会口头报告 研究背景 NK/T细胞淋巴瘤(NKTCL)是一种侵袭性非霍奇金淋巴瘤亚型，通常伴有EBV病毒感染 2 。目前尚无标准治疗方案。对于早期NKTCL，推荐采用放疗同时联合或序贯含门冬酰胺酶(Asp)的化疗方案，5年总生存率为55%-90%。对于晚期患者，推荐使用含Asp的化疗，如SMlLE方案(地塞米松+甲氨蝶呤+异环磷酰胺+左旋门冬酰胺酶+依托泊苷)，5年总生存率为30-40% 3,4 。 PD-1抑制剂已在研究中显示出对NKTCL有效。EBV感染与NKTCL密切相关，并导致JAK-STAT信号通路激活以及PD-L1/2表达增加。细胞毒性化疗药物通过多种机制刺激肿瘤特异性免疫反应，SMlLE方案对NKTCL有效但毒性大 3，4 ，因此本研究保留3种成分(甲氨蝶呤、培门冬酶和依托泊苷)，在细胞毒性治疗方案中加入PD-1抑制剂以探讨PD-1单克隆抗体卡瑞利珠单抗联合培门冬酶、依托泊苷、高剂量甲氨蝶呤(CLAMP方案)治疗NKTCL患者的疗效和安全性。 研究设计 这项单臂2期研究纳入NKTCL患者。患者分为两组：A组为早期(Ann Arbor分期I/II)患者；B组为晚期(Ann Arbor分期III/IV)和复发/难治性(RR)患者。A组患者行受累野放疗联合3-4个周期的CLAMP治疗，B组给予6个周期的CLAMP治疗。CLAMP方案给药如下：培门冬酶(2500U/m2 d1，最大剂量3750U)，依托泊苷(100mg/m2 d1-3)，大剂量甲氨蝶呤(HD-MTX，3g/m2 d4)，卡瑞利珠单抗(200mg d7)。在放疗后或每2个周期化疗后评估疗效，并于基线、C5D1化疗前2-3d、末次化疗后8周进行PET/CT检查。在前2年每3个月进行1次随访，之后每6个月进行1次随访。 研究主要终点为客观缓解率(ORR)和完全缓解率(CRR，根据Lugano 2014标准，基于PET/CT和MRI判定)，次要终点为无进展生存期(PFS)、总生存期(OS)以及安全性。 图1. 研究设计 研究结果 1.患者基线 2020年7月至2022年12月共纳入41例NK/T细胞淋巴瘤患者，36例为新诊断患者，5例为复发患者。其中14例患者为中枢神经系统(CNS)侵犯高风险，伴有2-4个NKPI危险因素(Ann Arbor期III或IV期、B症状、局部淋巴结受累、乳酸脱氢酶升高)，1例合并噬血细胞综合征(HLH)。 表1. 患者基线特征 2.临床疗效 放疗结束时，A组ORR达到100%(19/19)，CRR为89.5%(17/19)，部分缓解(PR)率为10.5%(2/19)。 表2. A组放疗结束时的疗效结果 治疗结束时，所有患者CRR为87.8%(36/41)，PR率为7.3%(3/41)，ORR达95.1%(39/41)，A组患者ORR为100%(19/19)，B组患者ORR为90.9%(20/22)；B组仅有2例患者在治疗过程中出现进展。合并HLH的患者获得完全缓解，无病达12个月以上。 表3. 治疗结束后的疗效结果 在随访期间，没有患者发生HLH或中枢神经系统受累。中位随访时间为21个月。整个队列的2年PFS率为72.8%，A组和B组2年PFS率分别为91.7%和53.8%。2年OS率为88.0%，A组和B组2年OS率分别为91.7%和77.5%。A组和B组均未达到中位缓解持续时间。安全性方面，整体可控。 图2. 2年的PFS率 图3. 2年的OS率 图4. 肿瘤反应与持续时间 研究结论 研究结果证明，卡瑞利珠单抗联合培门冬酶、依托泊苷和大剂量甲氨蝶呤(CLAMP方案)治疗NKTCL患者具有良好的疗效和安全性，并提示可减少中枢神经系统受累和HLH的发生，有望成为NK/T细胞淋巴瘤患者新的治疗选择。 《“健康中国2030”规划纲要》提出“到2030年，要实现总体癌症5年生存率提高15%”的战略目标。抗肿瘤药物是癌症患者控制和治疗疾病的重要希望。作为创新型国际化制药企业，恒瑞医药长期坚持“科技为本，为人类创造健康生活”的使命，针对肿瘤等严重威胁人类生命健康的疾病开展科研攻关，已上市的16款创新药中抗肿瘤创新药占比过半。未来，恒瑞医药将继续坚持“以患者为中心”的理念，重创新，强研发，力争研制出更多的新药、好药，服务“健康中国”，惠及全球患者。 参考文献： [1] Tao Liu, Liling Zhang, et al. CLAMP: A phase II prospective study of camrelizumab combined with pegaspargase, etoposide, and high-dose methotrexate in patients with natural killer (NK)/T-cell lymphoma.2024 ASCO Oral 7002. [2] NCCN Guidelines, Version 2.2024. [3] Qi SN, Li YX. First-line immunochemotherapy for extranodal natural killer/T cell lymphoma. Lancet Haematol. 2024;11(5):e311-e313. doi:10.1016/S2352-3026(24)00071-1 [4] Tse E, Zhao WL, Xiong J, Kwong YL. How we treat NK/T-cell lymphomas. J Hematol Oncol. 2022;15(1):74. Published 2022 Jun 3. doi:10.1186/s13045-022-01293-5 声明： 1.本新闻旨在分享学术前沿动态，仅供医疗卫生专业人士基于学术目的参阅，非广告用途。 2. 恒瑞医药不对任何药品和/或适应症作推荐。 3.本新闻中涉及的信息仅供参考，请遵从医生或其他医疗卫生专业人士的意见或指导。医疗卫生专业人士作出的任何与治疗有关的决定应根据患者的具体情况并遵照药品说明书。

2024年美国临床肿瘤学会(ASCO)年会将于5月31日到6月4日在芝加哥举办，是世界上规模最大、学术水平最高、最具权威性的临床肿瘤学会议，会议汇集了全球肿瘤学医生和专业人士、患者倡导者、工业界代表和主要媒体，共同探讨当前国际最前沿的研究发现和临床试验成果。ASCO成立于1964年,是世界上最大、最具影响力的肿瘤专业学术组织,致力于癌症的预防、治疗及改善对患者的护理。ASCO在全球150多个国家和地区拥有超过45,000名成员。4月24日晚，ASCO官网公布了本次大会的研究标题，几十余名中国专家将在世界舞台上展示其研究成果，报告涵盖了多个瘤种的最新治疗策略和技术，展示了中国在全球癌症研究中的重要地位和贡献。世易编辑团队精心整理了中国专家们的研究报告，供您参考。全体大会报告Osimertinib (osi) after definitive chemoradiotherapy (CRT) in patients (pts) with unresectable stage (stg) III epidermal growth factor receptor-mutated (EGFRm) NSCLC: Primary results of the phase 3 LAURA study.  Abstract: LBA4    · Suresh S. Ramalingam教授，美国埃默里大学Winship癌症研究所· 陆舜 教授，上海交通大学附属胸科医院    口头报告Lung Cancer—Non-Small Cell MetastaticSacituzumab tirumotecan (SKB264/MK-2870) in combination with KL-A167 (anti-PD-L1) as first-line treatment for patients with advanced NSCLC from the phase II OptiTROP-Lung01 study.    Abstract: 8502    · 方文峰 教授，中山大学肿瘤防治中心    Ivonescimab combined with chemotherapy in patients with EGFR-mutant non-squamous non-small cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor treatment (HARMONi-A): A randomized, double-blind, multi-center, phase 3 trial.    Abstract: 8508    · 张力 教授，中山大学肿瘤防治中心    Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers    Adjuvant icotinib of 12 months or 6 months versus observation following adjuvant chemotherapy for resected EGFR-mutated stage II–IIIA non-small-cell lung cancer (ICTAN, GASTO1002): A randomized phase 3 trial.    Abstract: 8004    ·王思愚 教授，中山大学肿瘤防治中心    A phase II randomized trial evaluating consolidative nivolumab in locally advanced non-small cell lung cancer post neoadjuvant chemotherapy plus nivolumab and concurrent chemoradiotherapy (GASTO-1091).    Abstract: 8008    · 刘慧 教授，中山大学肿瘤防治中心    Taiwan national lung cancer early detection program for heavy smokers and non-smokers with family history of lung cancer.   Abstract: 8009    · Pan-Chyr Yang, MD, PhD，台湾大学医学院  Gastrointestinal Cancer—Colorectal and Anal  Neoadjuvant treatment of IBI310 (anti-CTLA-4 antibody) plus sintilimab (anti-PD-1 antibody) in patients with microsatellite instability-high/mismatch repair-deficient colorectal cancer: Results from a randomized, open-labeled, phase Ib study.    Abstract: 3505    · 徐瑞华 教授，中山大学肿瘤防治中心    Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant   Phase I study of CN201, a novel CD3xCD19 IgG4 bispecific antibody, in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia.    Abstract: 6505     · 王迎 教授，中国医学科学院血液病医院     Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia    CLAMP: A phase II prospective study of camrelizumab combined with pegaspargase, etoposide, and high-dose methotrexate in patients with natural killer (NK)/T-cell lymphoma.    Abstract: 7002    · 刘涛 教授，华中科技大学同济医学院附属协和医院    Tucidinostat plus R-CHOP in previously untreated diffuse large B-cell lymphoma with double expression of MYC and BCL2: An interim analysis from the phase III DEB study.    Abstract: LBA7003    · 赵维莅 教授，上海交通大学医学院附属瑞金医院    Hematologic Malignancies—Plasma Cell DyscrasiaPhase 3 study results of isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) versus VRd for transplant-ineligible patients with newly diagnosed multiple myeloma (IMROZ).    Abstract: 7500      ·Thierry Facon, MD，University of Lille, CHU Lille·刘卓刚 教授，中国医科大学附属盛京医院Central Nervous System Tumors    Efficacy and safety of the vebreltinib in patients with previously treated, secondary glioblastoma/IDH mutant glioblastoma with PTPRZ1-METFUsion GENe (FUGEN): A randomised, multicentre, open-label, phase II/III trial.    Abstract: 2003    · Zhaoshi Bao, MD, PhD，首都医科大学附属北京天坛医院    High-dose almonertinib in treatment-naïve EGFR-mutated NSCLC with CNS metastases: Efficacy and biomarker analysis.    Abstract: 2007       · 范云 教授，浙江省肿瘤医院    SarcomaUpdated efficacy results of olverembatinib (HQP1351) in patients with tyrosine kinase inhibitor (TKI)-resistant succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GIST) and paraganglioma.    Abstract: 11502         · 邱海波 教授，中山大学肿瘤防治中心    Sintilimab, doxorubicin and ifosfamide (AI) as first-line treatment in patients with advanced undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), myxoid liposarcoma (MLPS) and de-differentiated liposarcoma (DDLPS): A single-arm phase 2 trial.    Abstract: 11505    · 罗志国 教授，复旦大学附属肿瘤医院    ARTEMIS-002: Phase 2 study of HS-20093 in patients with relapsed or refractory osteosarcoma.    Abstract: 11507    · 谢璐 教授，北京大学人民医院    Head and Neck Cancer    Adjuvant PD-1 blockade with camrelizumab in high-risk locoregionally advanced nasopharyngeal carcinoma (DIPPER): A multicenter, open-label, phase 3, randomized controlled trial.    Abstract: LBA6000    · 刘需 教授，中山大学肿瘤防治中心    Tislelizumab versus placebo combined with induction chemotherapy followed by concurrent chemoradiotherapy and adjuvant tislelizumab or placebo for locoregionally advanced nasopharyngeal carcinoma: Interim analysis of a multicenter, randomized, placebo-controlled, double-blind, phase 3 trial.    Abstract: 6001       · 陈秋燕 教授，中山大学肿瘤防治中心    Endostar combined with concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone for locoregionally advanced nasopharyngeal carcinoma (LA-NPC): A phase III, prospective, randomised-controlled, multicenter clinical trial.    Abstract: 6002      · 康敏 教授，广西医科大学第一附属医院    Developmental Therapeutics—ImmunotherapyClaudin18.2-targeted chimeric antigen receptor T cell-therapy for patients with gastrointestinal cancers: Final results of CT041-CG4006 phase 1 trial.    Abstract: 2501    · 齐长松 教授，北京大学肿瘤医院    A potential best-in-class BCMA-CD19 bispecific CART with advanced safety by self-inhibiting IFNG signaling during CRS.  Abstract: 2502     · Lei Xue    Efficacy and safety of LM-108, an anti-CCR8 monoclonal antibody, in combination with an anti-PD-1 antibody in patients with gastric cancer: Results from phase 1/2 studies.    Abstract: 2504    · Chang Liu, MD，北京大学肿瘤医院Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology    Phase I/II first-in-human study to evaluate the safety and efficacy of tissue factor-ADC MRG004A in patients with solid tumors.Abstract: 3002· Wungki Park, MD, MS，美国纪念斯隆凯瑟琳癌症中心· 张剑 教授，复旦大学附属肿瘤医院Updated safety and efficacy data of combined KRAS G12C inhibitor (glecirasib, JAB-21822) and SHP2 inhibitor (JAB-3312) in patients with KRAS p.G12C mutated solid tumors.    Abstract: 3008    · 赵军 教授，北京大学肿瘤医院    快速口头摘要报告 Lung Cancer—Non-Small Cell Metastatic    A multinational pivotal study of sunvozertinib in platinum pretreated non-small cell lung cancer with EGFR exon 20 insertion mutations: Primary analysis of WU-KONG1 study.    Abstract: 8513     · James Chih-Hsin Yang 教授，台大肿瘤中心    Efficacy and safety of taletrectinib in patients with advanced or metastatic ROS1+ non–small cell lung cancer: The phase 2 TRUST-I study.    Abstract: 8520    · 李玮 教授，同济大学附属上海市肺科医院    Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers    Overall survival of adebrelimab plus chemotherapy and sequential thoracic radiotherapy as first-line treatment for extensive-stage small cell lung cancer.    Abstract: 8014      · 陈大卫 教授，山东省肿瘤医院    Breast Cancer—Metastatic    ACE-Breast-02: A pivotal phase II/III trial of ARX788, a novel anti-HER2 antibody-drug conjugate (ADC), versus lapatinib plus capecitabine for HER2+ advanced breast cancer (ABC).  Abstract: 1020    · 胡夕春 教授，复旦大学附属肿瘤医院    Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary    Efficacy and safety of cadonilimab in combination with pulocimab and paclitaxel as second-line therapy in patients with advanced gastric or gastroesophageal junction (G/GEJ) cancer who failed immunochemotherapy: A multicenter, double-blind, randomized trial.    Abstract: 4012    · 张小田 教授，北京大学肿瘤医院    Phase I study of C-CAR031, a GPC3-specific TGFβRIIDN armored autologous CAR-T, in patients with advanced hepatocellular carcinoma (HCC).    Abstract: 4019    · 章琦 教授，浙江大学医学院附属第一医院肝胆胰外科    Gastrointestinal Cancer—Colorectal and Anal    Total neoadjuvant treatment with long-course radiotherapy versus concurrent chemoradiotherapy in local advanced rectal cancer with high risk factors (TNTCRT): A multicenter, randomized, open-label, phase 3 trial.    Abstract: LBA3511       · Xin Wang, MD，四川大学华西医院    Phase I trial of hypoxia-responsive CEA CAR-T cell therapy in patients with heavily pretreated solid tumor via intraperitoneal or intravenous transfusion.    Abstract: 3514      · Hangyu Zhang，浙江大学医学院第一附属医院    Three-year disease-free survival after transanal vs. laparoscopic total mesorectal excision for rectal cancer (TaLaR): A randomized clinical trial.    Abstract: 3516      · 康亮 教授，中山大学附属第六医院    Genitourinary Cancer—Kidney and Bladder    Camrelizumab plus apatinib for previously treated advanced adrenocortical carcinoma: A single-arm, open-label, phase 2 trial.    Abstract: 4511    · Zhigong Wei，四川大学华西医院    Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant    Latest results of a phase 2 study of IMM01 combined with azacitidine (AZA) as the first-line treatment in adults with higher risk myelodysplastic syndromes (MDS).    Abstract: 6510    · Wei Yang，中国医科大学附属盛京医院     Safety and efficacy of CD7-CAR-T cell in patients with relapsed/refractory T-lymphoblastic leukemia/lymphoma: Phase I dose-escalation/dose-expansion study.    Abstract: 6515     · Lijuan Hu, MD, 北京大学人民医院    Hematologic Malignancies—Plasma Cell Dyscrasia   OriCAR-017, a novel GPRC5D-targeting CAR-T, in patients with relapsed/refractory multiple myeloma: Long term follow-up results of phase 1 study (POLARIS).    Abstract: 7511    · Shan Fu，浙江大学医学院附属第一医院    Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia    Timdarpacept (IMM01) in combination with tislelizumab in prior anti-PD-1 failed classical Hodgkin lymphoma: An open label, multicenter, phase II study (IMM01-04) evaluating safety as well as preliminary anti-tumor activity.    Abstract: 7017    · Zhenjiu Wang, MD    Gynecologic Cancer    Efficacy and safety of sintilimab plus paclitaxel and cisplatin as neoadjuvant therapy for locally advanced cervical cancer: A phase II trial.    Abstract: 5512  ·刘继红 教授，中山大学肿瘤防治中心    Nimotuzumab plus concurrent chemoradiotherapy for locally advanced cervical squamous cell carcinoma: The randomized, phase 3 CC3 study.    Abstract: 5514 ·王俊杰 教授，北京大学第三人民医院    A phase III randomized, double-blinded, placebo-controlled study of suvemcitug combined with chemotherapy for platinum-resistant ovarian cancer (SCORES).    Abstract: LBA5516    · 袁光文 教授，中国医学科学院肿瘤医院    Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): A final overall survival analysis of a multicenter, open-label, randomized, phase 3 trial.    Abstract: 5520    · 臧荣余 教授，复旦大学附属中山医院    Head and Neck Cancer    Preliminary results of phase I/II study to evaluate safety and efficacy of combination pucotenlimab with epidermal growth factor receptor-ADC (EGFR-ADC) MRG003 in patients with EGFR positive solid tumors.    Abstract: 6013    · 阮丹云 教授，中山大学肿瘤防治中心    Covalent FAPI PET enables accurate management of medullary thyroid carcinoma: a prospective single-arm comparative clinical trial.    Abstract: LBA6018    · Ziren Kong, MD,  中国医学科学院北京协和医学院    Sarcoma    A phase II study of anlotinib and an anti-PDL1 antibody in patients with alveolar soft part sarcoma: Results of expansion cohorts.    Abstract: 11515     · 刘佳勇 教授，北京大学肿瘤医院    Phase 1 study of NB003, a broad-spectrum KIT/PDGFRα inhibitor, in patients with advanced gastrointestinal stromal tumors (GIST).    Abstract: 11518    · 李健 教授，北京大学肿瘤医院    Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology    Results of a phase 1/2 study of MHB088C: A novel B7H3 antibody-drug conjugate (ADC) incorporating a potent DNA topoisomerase I inhibitor in recurrent or metastatic solid tumors.    Abstract: 3012    · 沈琳教授，北京大学肿瘤医院    9MW2821, a nectin-4 antibody-drug conjugate (ADC), in patients with advanced solid tumor: Results from a phase 1/2a study.    Abstract: 3013       · 张剑 教授，复旦大学附属肿瘤医院    Developmental Therapeutics—Immunotherapy    Phase I study of GUCY2C CAR-T therapy IM96 in patients with metastatic colorectal cancer.    Abstract: 2518    · 齐长松 教授，北京大学肿瘤医院    Safety and preliminary efficacy results of IBI389, an anti-CLDN18.2/CD3 bispecific antibody, in patients with solid tumors and gastric or gastro-esophageal tumors: A phase 1 dose escalation and expansion study.    Abstract: 2519       · 郑莉 教授，四川大学华西医院    Symptom Science and Palliative Care    Effect of nurse-led multi-disciplinary treatment on patients with head and neck tumors: A randomized controlled trial.    Abstract: 12013       · Jingjing Wang, MD，四川大学华西医院肿瘤中心    临床科学研讨会A phase 1/2 study of the TORC1/2 inhibitor onatasertib combined with toripalimab in patients with advanced solid tumors: Cervical cancer cohort.    Abstract: 5509    · Hui Xie，德琪医药有限公司临床研发部    KRYSTAL-12: Phase 3 study of adagrasib versus docetaxel in patients with previously treated advanced/metastatic non-small cell lung cancer (NSCLC) harboring a KRASG12C mutation.    Abstract: LBA8509    · Tony S. K. Mok 教授，香港大学      Sacituzumab tirumotecan (SKB264/MK-2870) in patients (pts) with previously treated locally recurrent or metastatic triple-negative breast cancer (TNBC): Results from the phase III OptiTROP-Breast01 study.    Abstract: 104         · 樊英 教授，中国医学科学院肿瘤医院    Efficacy of disitamab vedotin (RC48) plus tislelizumab and S-1 as first-line therapy for HER2-overexpressing advanced stomach or gastroesophageal junction adenocarcinoma: A multicenter, single-arm, phase II trial (RCTS).    Abstract: 4009     · 刘联 教授，山东大学齐鲁医院    A novel and uniquely designed bispecific antibody (LBL-024) against PD-L1 and 4-1BB in patients with advanced malignant tumors and neuroendocrine carcinoma: A report of safety and robust efficacy of LBL-024 monotherapy in phase I/II, first-in-human, open-label, multicenter, dose escalation/expansion study.    Abstract: 4010       · 张盼盼 医生，北京大学肿瘤医院    Safety and efficacy of IBI389, an anti-CLDN18.2/CD3 bispecific antibody, in patients with advanced pancreatic ductal adenocarcinoma: Preliminary results from a phase 1 study.    Abstract: 4011    · 郝继辉 教授，天津医科大学肿瘤医院    Neoadjuvant sintilimab and platinum-doublet chemotherapy followed by transoral robotic surgery for HPV-associated resectable oropharyngeal cancer: Single-arm, phase II trial.    Abstract: 6011    · 宋明 教授，中山大学肿瘤防治中心      BiG 十周年预告  本次BiG十周年庆典，将首次分为国内和国际篇章，以原创科学和临床需求为出发点，讨论创新技术平台和创新疗法（PROTACT/分子胶、双抗/ADC、siRNA/ASO、CGT、AI制药）的重大进展和发展前景，十年一药曙光现，大浪淘沙始见金！▼报名参会 会议门票：审核制(免费)；含主论坛+分论坛，不含餐；优先biotech/Pharma、临床、院校科学家共建Biomedical创新生态圈！如何加入BiG会员？