A Phase 2, Open-label, Single Arm Study of Combined HAIC, Lenvatinib and Pucotenlimab as Conversion Therapy for Unresectable Intrahepatic Cholangiocarcinoma

This is an open-label, single-arm, phase 2 study. The purpose of study is to evaluate the feasibility and safety of hepatic artery infusion chemotherapy combined with lenvatinib and pucotenlimab as conversion therapy for unresectable intrahepatic cholangiocarcinoma.

开始日期2024-01-31

申办/合作机构

上海市同济医院

[+1]

NCT06192784 / Recruiting临床2期IIT

A Phase 2, Open-label, Single Arm Study of Combined Drug-eluting Beads-TACE, Lenvatinib and Pucotenlimab as Conversion Therapy for Unresectable Intrahepatic Cholangiocarcinoma

This is an open-label, single-arm, phase 2 study. The purpose of study is to evaluate the feasibility and safety of drug eluting beads-transcatheter arterial chemoembolization combined with lenvatinib and pucotenlimab as conversion therapy for unresectable intrahepatic cholangiocarcinoma.

开始日期2023-12-09

申办/合作机构

上海市同济医院

[+1]

NCT06129955 / Not yet recruiting临床2期IIT

A Phase II Clinical Study on the Efficacy and Safety of Pucotenlimab Combined With Lenvatinib as a Neodjuvant Therapy for Non Clear Cell Renal Cell Carcinoma With Indications for Partial Nephrectomy But High Surgical Risk: A Single Arm Approach

Through the neoadjuvant treatment with a combination of Pucotenlimab and Lenvatinib, it eventually enables the successful and safe implementation of partial nephrectomy in patients with localized renal cancer, who have indications for nephron-sparing surgery but face significant difficulty in kidney preservation (T1b with an endophytic component ≥75% or T2).

开始日期2023-11-11

申办/合作机构

中山大学

100 项与普特利单抗相关的临床结果

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100 项与普特利单抗相关的转化医学

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100 项与普特利单抗相关的专利（医药）

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项与普特利单抗相关的文献（医药）

2023-12-01·Cell Reports Medicine

Pucotenlimab in patients with advanced mismatch repair-deficient or microsatellite instability-high solid tumors: A multicenter phase 2 study

Article

作者: Yin, Xianli ; Yu, Junyan ; Liang, Xinjun ; Li, Shengmian ; Liu, Zhihui ; Wang, Ke ; Zeng, Shan ; Liu, Yunpeng ; Dou, Yiwei ; Luo, Suxia ; Fan, Qingxia ; Wang, Fen ; Li, Enxiao ; Zhuang, Zhixiang ; Zhang, Shu ; Liu, Qian ; Zhang, Jingdong ; Huang, Jing ; Xu, Nong ; Kou, Xiaoge ; Zhu, Xiaodong ; Wang, Hui ; Song, Yan ; Bai, Yuxian ; Ma, Taiyang ; Shu, Yongqian ; Zhang, Bo ; Zhong, Haijun ; He, Yifu

We report a multicenter, phase 2 study evaluating the efficacy of pucotenlimab, an anti-PD-1 antibody, in patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, and potential biomarkers for response. Overall, 100 patients with previously treated, advanced solid tumors centrally confirmed as dMMR or MSI-H received pucotenlimab at 200 mg every 3 weeks. The most common cancer type is colorectal cancer (n = 71). With a median follow-up of 22.5 months, the objective response rate is 49.0% (95% confidence interval 38.86%-59.20%) as assessed by the independent review committee, while the median progression-free survival and overall survival have not been reached. Grade ≥3 treatment-related adverse events were observed in 18 patients. For the biomarker analysis, responders are enriched in patients with mutations in the KMT2D gene. Pucotenlimab is an effective treatment option for previously treated advanced dMMR/MSI-H solid tumors, and the predictive value of KMT2D mutation warrants further research. This study is registered with ClinicalTrials.gov: NCT03704246.

2023-09-01·Cancer communications (London, England)

Low level of ARID1A contributes to adaptive immune resistance and sensitizes triple-negative breast cancer to immune checkpoint inhibitors.

Article

作者: Ni, Ting ; Li, Bin ; Shao, Zhi-Ming ; Yang, Meng-Di ; Tao, Zhong-Hua ; Wang, Bi-Yun ; Yang, Yu ; Zhang, Jian ; Wang, Ye ; Huang, Sheng-Lin ; Huang, Lei-Huan ; Jin, Juan ; Hu, Xi-Chun ; Chen, Xin-Yu

BACKGROUND:

Immune checkpoint inhibitors (ICIs) shed new light on triple-negative breast cancer (TNBC), but only a minority of patients demonstrate response. Therefore, adaptive immune resistance (AIR) needs to be further defined to guide the development of ICI regimens.

METHODS:

Databases, including The Cancer Genome Atlas, Gene Ontology Resource, University of California Santa Cruz Genome Browser, and Pubmed, were used to screen epigenetic modulators, regulators for CD8⁺ T cells, and transcriptional regulators of programmed cell death-ligand 1 (PD-L1). Human peripheral blood mononuclear cell (Hu-PBMC) reconstruction mice were adopted for xenograft transplantation. Tumor specimens from a TNBC cohort and the clinical trial CTR20191353 were retrospectively analyzed. RNA-sequencing, Western blotting, qPCR and immunohistochemistry were used to assess gene expression. Coculture assays were performed to evaluate the regulation of TNBC cells on T cells. Chromatin immunoprecipitation and transposase-accessible chromatin sequencing were used to determine chromatin-binding and accessibility.

RESULTS:

The epigenetic modulator AT-rich interaction domain 1A (ARID1A) gene demonstrated the highest expression association with AIR relative to other epigenetic modulators in TNBC patients. Low ARID1A expression in TNBC, causing an immunosuppressive microenvironment, promoted AIR and inhibited CD8⁺ T cell infiltration and activity through upregulating PD-L1. However, ARID1A did not directly regulate PD-L1 expression. We found that ARID1A directly bound the promoter of nucleophosmin 1 (NPM1) and that low ARID1A expression increased NPM1 chromatin accessibility as well as gene expression, further activating PD-L1 transcription. In Hu-PBMC mice, atezolizumab demonstrated the potential to reverse ARID1A deficiency-induced AIR in TNBC by reducing tumor malignancy and activating anti-tumor immunity. In CTR20191353, ARID1A-low patients derived more benefit from pucotenlimab compared to ARID1A-high patients.

CONCLUSIONS:

In AIR epigenetics, low ARID1A expression in TNBC contributed to AIR via the ARID1A/NPM1/PD-L1 axis, leading to poor outcome but sensitivity to ICI treatment.

2023-04-03·Scientific reports

HX009, a novel BsAb dual targeting PD1 x CD47, demonstrates potent anti-lymphoma activity in preclinical models.

Article

作者: Xiong, Lingxin ; He, Xiangfei ; Ke, Hang ; Sun, Ruilin ; Zhang, Faming ; Ju, Cunxiang ; Zhang, Lei ; Chen, Cen ; O'Connor, Owen A. ; Wang, Jingjing ; Mao, Binchen ; Guo, Sheng ; Li, Qi-Xiang ; An, Xiaoyu ; Wang, Yueying ; Tu, Xiaolong

Both PD1/PD-L1 and CD47 blockades have demonstrated limited activity in most subtypes of NHL save NK/T-cell lymphoma. The hemotoxicity with anti-CD47 agents in the clinic has been speculated to account for their limitations. Herein we describe a first-in-class and rationally designed bispecific antibody (BsAb), HX009, targeting PD1 and CD47 but with weakened CD47 binding, which selectively hones the BsAb for tumor microenvironment through PD1 interaction, potentially reducing toxicity. In vitro characterization confirmed: (1) Both receptor binding/ligand blockade, with lowered CD47 affinity; (2) functional PD1/CD47 blockades by reporter assays; (3) T-cell activation in Staphylococcal-enterotoxin-B-pretreated PBMC and mixed-lymphocyte-reaction. In vivo modeling demonstrated antitumor activity in Raji-B and Karpass-229-T xenograft lymphomas. In the humanized mouse syngeneic A20 B-lymphoma (huCD47-A20) HuGEMM model, which has quadruple knocked-in hPD1xhPD-L1xhCD47xhSIRPα genes and an intact autologous immune-system, a contribution of effect is demonstrated for each targeted biologic (HX008 targeting PD1 and SIRPα-Fc targeting CD47), which is clearly augmented by the dual targeting with HX009. Lastly, the expression of the immune-checkpoints PD-L1/L2 and CD47 seemed co-regulated among a panel of lymphoma-derived-xenografts, where HX009 maybe more effective in those with upregulated CD47. Our data warrants HX009's further clinical development for treating NHLs.

141

项与普特利单抗相关的新闻（医药）

2024-04-25

·BiG生物创新社

ASCO 2024丨这些中国临床专家，将分享最新重磅研究

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？

ASCO会议临床结果

2024-04-22

·同写意

癌王“杀手”浮出水面？

本次培训针对CGT企业或研发机构有一定CMC基础的工艺和质量主管进阶提升，讲述工艺与治疗关键点，给与尽可能多的避坑指南，帮助其成为独当一面的CMC专家。信吗？被称为“癌中之王”的胰腺癌的城池，正在不断被攻破。4月4日，在公布CAN-2409联合伐昔洛韦和化疗用于交界性可切除胰腺癌获得积极的II期研究数据后，Candel Therapeutics股价飙升约281%。稀缺造就爆炒。股价暴涨背后，是由于胰腺癌药物市场仍缺乏有效的靶向或免疫疗法。存在巨大的临床未满足需求。此次在胰腺癌中取得突破的溶瘤病毒疗法，是肿瘤治疗领域的新热点，机构预测其市场空间可达数百亿美元，媲美双抗、ADC的市场规模。国内药企中，乐普生物已抢占溶瘤病毒疗法的先机。此外，还有多种药物在积极攻克胰腺癌这块“硬骨头”，包括NALIRIFOX化疗新方案、PARP抑制剂、双抗和Claudin18.2靶向药物等。一场关于胰腺癌的攻坚战正在打响。1Candel股价暴涨背后Candel Therapeutics成立于1999年，是一家主攻溶瘤病毒疗法的癌症生物技术公司，于2021年在纳斯达克上市，目前已布局多款溶瘤病毒疗法管线，其中进展最快的便是前文提到的CAN-2409。目前，CAN-2409正在开展针对前列腺癌、非小细胞肺癌和胰腺癌的临床试验。其中，前列腺癌适应症已进入Ⅲ期阶段，其余两个均处于Ⅱ期阶段。Candel Therapeutics的研发管线图片来源：公司官网Candel股价单日暴涨280.95%，正是由于CAN-2409在非转移性胰腺癌随机II期临床试验中取得了积极的中期数据：截至2024年3月29日数据，在边缘性可切除胰腺导管腺癌（PDAC）中，使用CAN-2409进行实验治疗后，预估中位总生存期显著改善，mOS为28.8个月，而对照组仅为12.5个月；24个月时，接受CAN-2409治疗的患者生存率为71.4%，而对照组的生存率为16.7%；36个月时，CAN-2409组的生存率为47.6%，而对照组为16.7%。CAN-2409还显示出良好的耐受性，没有显著的额外局部或全身毒性。正如Candel总裁兼首席执行官Paul Peter Tak博士所言：“传统免疫疗法未能改善胰腺癌的治疗效果，原因在于高度免疫抑制的肿瘤微环境，其中很大程度上缺乏免疫细胞。”实际上，胰腺癌既诊断困难又极难攻克，一直缺乏有效的靶向或免疫疗法，因而被称为“癌中之王”，存在巨大的临床未满足需求。这也是刺激Candel股价暴涨的重要外因。胰腺癌是一种非常具有挑战性的癌症，早期发现率仅5%-7%，多数患者在发现时已进入晚期，且治疗手段有限，导致胰腺癌患者的总生存期较短，仅为6-9个月。据NCCN指南资料显示，一线治疗晚期胰腺癌的ORR一般不超过30%，mPFS低于6个月，mOS低于10个月；在接受二线治疗后，ORR约为7.7%，mPFS约为3个月，mOS约为6个月。不过，溶瘤病毒疗法作为肿瘤治疗领域新热点，又在胰腺癌中显示出治疗潜力，无疑能获得资本市场的青睐。另一家主攻溶瘤病毒疗法的CG Oncology公司，上市首日股价即暴涨近100%。这不免让人好奇，溶瘤病毒疗法这个半路杀出的“黑马”，究竟是“何方神圣”？2溶瘤病毒疗法“何方神圣”？乐普生物抢占先机溶瘤病毒疗法是一种利用病毒来治疗癌症的方法，主要通过裂解肿瘤细胞和激活机体的免疫反应两种原理来杀伤肿瘤细胞，具备高靶向性、肿瘤杀伤途径多、不良反应小等优势。在治疗过程中，这些溶瘤病毒会进入癌症患者的体内，然后寻找并感染癌细胞，一旦成功感染，就会在癌细胞内部大量复制，就像病毒在癌细胞里“安营扎寨”并“招兵买马”。随着病毒数量的增多，它们会破坏癌细胞的内部结构，最终导致癌细胞裂解和死亡。另外，溶瘤病毒还能激活患者自身的免疫系统来一起对抗癌症。当溶瘤病毒杀死癌细胞时，会释放出一些特殊的物质，这些物质就像是“信号弹”，吸引人体的免疫细胞前来攻击更多的癌细胞。目前，全球在研溶瘤病毒药物的病毒种类，主要以腺病毒、单纯疱疹病毒、痘苗病毒为主，适应症覆盖黑色素瘤、结直肠癌、胰腺癌、非小细胞肺癌、肝细胞癌、头颈部鳞状细胞癌、胶质瘤、卵巢癌等。抗肿瘤机制独特且可针对诸多实体瘤，溶瘤病毒疗法的市场潜力必然不容小觑。根据弗若斯特沙利文数据，2021年全球溶瘤病毒治疗药物市场总额达0.6亿美元，预计到2025年、2030年将分别达到67.9亿美元、247.9亿美元。2017-2030E全球溶瘤病毒治疗药物市场规模资料来源：弗若斯特沙利文，太平洋证券整理目前，全球已有3款溶瘤药物获批上市，包括第一三共Delytact（针对恶性胶质瘤）、安进Imlygic（针对黑色素瘤）、三维生物的安柯瑞（联用化疗治疗鼻咽癌），其中前两款的病毒类型为单纯疱疹病毒，后者为腺病毒。更重要的是，溶瘤病毒疗法不仅能单药治疗，还可与放疗、化疗药物、靶向疗法、细胞疗法和免疫检查点抑制剂等联合应用，技术优势显著。例如，CG Oncology公司研发的CG0070正在开展两项Ⅲ期临床试验，包括一项高危、卡介苗（BCG）无反应的非肌层浸润性膀胱癌（NMIBC）试验和一项中风险NMIBC试验，以及一项联合Pembrolizumab（Keytruda，K药）治疗高危、BCG无反应NMIBC疾病的II期试验。从临床数据看，CG0070针对高危、BCG无反应NMIBC患者的完全缓解（CR）率达到75.7%，单药治疗的有效性和安全性表现优于K药和基因疗法Adstiladrin，而且小样本的临床II期试验CORE-001显示CG0070联用PD-1有望进一步提升疗效。K药于2017年获FDA批准治疗MSI-H或dMMR实体瘤（包括胰腺癌）患者，之后又于2020年获批应用于高肿瘤突变负荷的癌症患者（包括胰腺癌）。CG0070与K药的联用，已经擦出了火花。2019年，乐普生物从CG Oncology引进了CG0070的大中华区权益，目前正在开展用于BCG无应答NMIBC的I期临床试验，后续有望开展桥接试验，快速实现上市。此外，以PD-1单抗为基石药物的乐普生物，也开展了自身核心产品普特利单抗联用CG0070治疗BCG无应答NMIBC的临床试验，颇有看点。3“癌王”攻坚战正在打响春风得意马蹄疾，一日看尽长安花。现阶段，胰腺癌治疗药物已取得许多新的突破，包括化疗方案的迭代和靶向药物的获批。由于多数胰腺癌患者在发现时已进入晚期，失去手术机会，化疗成为主要治疗方案，包括FOLFIRINOX方案（氟尿嘧啶+亚叶酸钙+伊立替康+奥沙利铂）、Gem+NabP方案（紫杉醇+吉西他滨）和S-IROX方案（替吉奥+伊立替康+奥沙利铂）。其中，Gem+NabP方案是胰腺癌一线标准治疗方案。然而，法国公司益普生（Ipsen）研发的NALIRIFOX方案（伊立替康脂质体+5-氟尿嘧啶/亚叶酸+奥沙利铂），不仅在头对头试验中打败了Gem+NabP方案，还于今年2月获美国FDA批准用于转移性胰腺癌患者的一线治疗。根据Ⅲ期研究NAPOLI 3结果显示，NALIRIFOX方案、Gem+NabP方案一线治疗转移性胰腺癌患者的中位总生存期（OS）分别为11.1个月、9.2个月，中位无进展生存期（PFS）分别为7.4个月、5.6个月，客观缓解率（ORR）分别为41.8%、36.2%。此外，还有一些靶向药物也成功获批治疗胰腺癌，包括Erlotinib（厄洛替尼）、Lynparza（奥拉帕利）、Larotrectinib（Vitrakvi）和Entrectinib（Rozlytrek）等。其中，阿斯利康研发的奥拉帕利，是全球首款获批上市的PARP抑制剂，自2014年以来已相继获批卵巢癌、乳腺癌、去势抵抗性前列腺癌和胰腺癌等多项适应症，2023年销售额高达28.11亿美元。据研究结果显示：与对照组相比，奥拉帕利使gBRCAm转移性胰腺癌患者的无进展生存期延长了近一倍（中位PFS：7.4个月 vs 3.8个月）、疾病进展或死亡风险显著降低了47%。国内药企方面，和黄医药布局了索凡替尼+卡瑞利珠单抗+白蛋白结合型紫杉醇+S-1（NASCA方案），相较AG方案（吉西他滨+白蛋白紫杉醇）带来更多获益；再鼎医药也针对PARP1/2抑制剂尼拉帕利开展了二线治疗晚期胰腺癌的临床研究。值得一提的是，康宁杰瑞研发的PD-L1/CTLA-4双抗KN046联合化疗一线治疗胰腺癌，已推进至临床Ⅲ期阶段。尤其在胰腺癌中高表达的Claudin18.2靶点，吸引了不少国内外药企争相布局，涉及单抗、ADC和CAR-T疗法等各种药物类型。Claudin18.2 ADC竞争格局（注：仅包含进入临床的管线品种）资料来源：华泰证券研报Claudin18.2单抗方面，包括安斯泰来Zolbetuximab（IMAB326）、创胜集团TST001；靶向Claudin18.2的ADC药物，包括礼来LM-302、康诺亚/乐普生物CMG901、君实生物JS-107和信达生物的IBI343等；靶向Claudin18.2的CAR-T疗法，科济药业布局了两款（CT041、CT048），传奇生物布局了LB-1904，均有开展针对胰腺癌的临床试验。此外，乐普生物研发的MRG004A，是国内首个申报临床的TF ADC，目前正在美国及中国进行Ⅰ/Ⅱ期临床研究，并已在胰腺癌、三阴性乳腺癌及宫颈癌中观察到抗肿瘤活性信号，且FDA已授予MRG004A用于治疗胰腺癌的孤儿药资格认定和快速通道资格。在TF ADC药物市场，全球仅有Seagen的Tivdak获批上市，获批适应症为宫颈癌、卵巢癌，未来或将有望拿下胰腺癌，再鼎医药拥有该药的中国权益。— 总结 — 可以看到，这场关于“癌王”胰腺癌的攻坚战，覆盖了各种各样的药物类型，打得可谓相当精彩。尤其Claudin18.2靶向药物，参与者众多，当前已进入竞争的白热化阶段，期待国产药企能从中突围。参考文献：1.各家公司的财报、公告、官网2.《20240225-生物医药Ⅱ行业周报：溶瘤病毒疗法初显峥嵘，乐普生物布局领先》，太平洋证券3.《攻克癌王的机会》，瞪羚社，2023-11-204.《CG Oncology首日大涨96%：核心产品溶瘤病毒疗法CG0070，乐普生物拥有大中华区权益》，医药笔记，2024-01-265.《显著延长“癌症之王”生存期！FDA批准一线治疗晚期胰腺癌的新疗法》，厚朴方舟，2024-02-18更多优质内容，欢迎关注↓↓↓

免疫疗法抗体药物偶联物临床3期临床2期

2024-04-11

·佰傲谷BioValley

国产PD-1成绩单：先发优势 VS 后起之秀

PD-1抑制剂作为目前最为成熟和有效的抗癌手段之一，受到了全球范围内的广泛追捧。自2014年首个PD-1抑制剂Opdivo上市以来，这一类药物已在数十种癌症类型中显著延长了患者的生存期，成为了不折不扣的癌症“救命神药”。2018年12月，首个国产PD-1抑制剂君实生物的特瑞普利单抗上市。短短5年的时间里，国产PD-1/PD-L1单抗的市场队伍已经壮大到了令人瞩目的规模。近期，随着各家企业发布年度财报，2023年国产PD-1的“成绩单”也陆续出炉。曾经的PD-1四小龙适应症一直是PD-1抑制剂的关键，业内一直有“得大适应症者得天下”的论调。在这方面，百济神州的替雷利珠单抗（百泽安）持续在适应症扩展上领先其他竞争对手，成为了最畅销的国产PD-1。2023年，替雷利珠单抗（百泽安）在医保范围又新增了2项一线治疗适应症（食管鳞状细胞癌、胃或胃食管结合部腺癌），且价格也有下调，再次成为了国产PD-1单抗中的榜首。替雷利珠单抗目前已有11项医保适应症，销售额达到38亿元，同比增长33%。在医保谈判后，替雷利珠单抗的价格调整为1253.53元/支，考虑到乙类医保目录报销比例为70%，患者每支替雷利珠单抗的实际费用仅为376元，年治疗费用低于13000元，进一步减轻了患者的经济负担。来源：药智头条除了百济神州的PD-1外，君实生物和信达生物的PD-1产品销售额显著增长，分别实现了9.19亿元和28亿元的销售额。信达生物的PD-1信迪利单抗在2022年销售额下滑后，去年再次强势反弹，目前共有7个适应症获得了NMPA批准。君实生物的特瑞普利单抗作为国内首个获批的PD-1单抗，销售额也在逐步走出低谷。财报显示，2023年，特瑞普利单抗销量上升23.50%至129.96万支，实现销售收入约9亿元，同比增长约25%。值得一提的是，在2023年十月，君实生物的特瑞普利单抗成为了首个成功出海的国产PD-1，获得了美国食品药品监督管理局（FDA）的批准。随后，百济神州宣布，FDA已批准其PD-1替雷利珠单抗上市，成为继君实生物之后的第二个成功进入美国市场的国产PD-1产品。恒瑞医药是唯一一家同时拥有PD-1和PD-L1两大单抗的药企。2021年，卡瑞利珠单抗年销售额曾一度超过40亿元，目前恒瑞医药还未披露2023年年报。后起之秀处于第二梯队的PD-1相关企业在2023年展现了不断超赶的势头。复宏汉霖的PD-1抑制剂斯鲁利单抗注射液在2023年实现了11亿元的收入，同比增长230.20%。这一产品上市不到两年，已成为国产PD-1领域的一匹黑马。延伸阅读：华丽转身的复宏汉霖，靠的是什么？同样上市不到两年的康方生物的卡度尼利单抗（开坦尼）作为首款获批上市的国产双抗(PD-1/CTLA-4)药物，于2022年6月获得了NMPA的附条件批准上市，用于治疗既往接受含铂化疗治疗失败的复发或转移性宫颈癌患者。2023年，卡度尼利单抗的销售额达到13.58亿元，同比增长149%。乐普生物和康宁杰瑞的PD-1产品虽然市场份额较低，但也实现了销售额的大幅增长。乐普生物的普特利单抗销售额突破了10亿元，同比增长了551.1%。康宁杰瑞的PD-L1单抗恩沃利单抗注射液实现了6.35亿元的收入，同比增长11.9%。随着国产PD-1抑制剂市场的不断扩大和产品的不断创新，中国的生物制药行业正在迅速崛起，为国内乃至世界各地的癌症患者带来了更多的希望和机会。参考资料：1.https://mp.weixin.qq.com/s/QVrjFS-x52RO5lMMKf6h6g本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处···

财报上市批准医药出海临床研究

100 项与普特利单抗相关的药物交易

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研发状态

适应症	最高研发状态	国家/地区	公司
胃腺癌	临床3期	中国更多	乐普生物科技股份有限公司更多
晚期胃癌	临床3期	中国更多	中山康方生物医药有限公司更多
晚期肝细胞癌	临床2期	中国更多	中山康方生物医药有限公司更多
MSI-H 实体瘤	临床2期	中国更多	杭州翰思生物医药有限公司更多
转移性三阴性乳腺癌	临床2期	中国更多	鼎康（武汉）生物医药有限公司更多

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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


NCT04750083 (ESMO2023) 人工标引	临床2期	非鳞状非小细胞肺癌一线 EGFR mutation \| ALK mutation	43	Pucotenlimab 200mg+pemetrexed+platinum	膚壓築鑰膚構遞範襯糧(積淵選鏇廠膚醖餘廠艱) = 鹽積鹽淵獵襯鹽淵顧衊獵廠鏇鹹窪鹹顧襯壓窪 (鬱鬱鹽壓憲窪鏇範鏇鹽, 38.9, 59.2) 更多	积极	2023-10-23
NCT05068453 (ASCO2023) 人工标引	临床1期	肝转移	10	Pucotenlimab+OH2	鹹選鏇製膚製窪範膚膚(鹹膚顧獵艱窪鹽範積窪) = 選範衊淵積膚淵蓋夢構選鑰糧窪積選齋獵憲鹽 (積廠襯壓觸憲醖蓋淵鏇 ) 更多	积极	2023-05-31
NCT04741165 (ASCO2023) 人工标引	临床2期	晚期肝细胞癌一线	75	Bevacizumab+Pucotenlimab (C1)	糧窪膚餘觸鹽築窪膚製(鬱夢遞繭鑰鏇獵膚齋襯) = 製餘製繭窪選蓋膚憲鹹襯壓窪簾選齋鹹餘獵廠 (構衊窪鏇衊鏇範膚壓製 ) 更多	积极	2023-05-26
NCT04741165 (ASCO2023) 人工标引	临床2期	晚期肝细胞癌一线	75	lenvatinib+Pucotenlimab (C2)	糧窪膚餘觸鹽築窪膚製(鬱夢遞繭鑰鏇獵膚齋襯) = 鬱積範顧獵積齋夢憲齋襯壓窪簾選齋鹹餘獵廠 (構衊窪鏇衊鏇範膚壓製 ) 更多	积极	2023-05-26
SABCS2023	临床1期	转移性三阴性乳腺癌一线	31	Pucotenlimab (HX008) + gemcitabine + cisplatin	憲蓋製衊蓋齋襯網積鑰(鹽鹹膚窪範鹽壓醖顧壓) = 願願廠鏇艱糧製蓋餘壓製選膚蓋鹹夢鹹餘積餘 (築膚範窪窪膚齋餘襯糧, 55.4% ~ 88.1%) 更多	积极	2023-04-24
NCT04749485 (Pubmed)	临床2期	局部晚期黑色素瘤	119	Pucotenlimab 3 mg/kg	鬱顧鑰壓窪構鏇製鹽構(鬱觸齋願積糧蓋構鑰廠) = 鏇蓋簾構憲構網鹽製觸襯築餘壓觸積鏇簾襯獵 (餘窪鹽壓窪鑰繭願遞構, 13.370% ~ 28.506%) 更多	-	2023-02-06
NCT03704246 (ASCO_GI2023) 人工标引	临床2期	MMRD实体瘤 \| MSI-H 实体瘤二线 MSI-H \| dMMR	100	200mg pucotenlimab	餘夢廠製鏇鏇夢鑰顧壓(壓鬱獵廠夢襯觸膚餘築) = 壓鏇遞壓築膚夢獵網鏇襯鑰鬱膚衊網夢築齋憲 (壓壓願顧鑰網網夢鑰餘, 38.86 ~ 59.20) 更多	积极	2023-01-24
CTR20191353 (Pubmed) 人工标引	临床1期	三阴性乳腺癌一线 triple-negative	31	Gemcitabine+Cisplatin+Pucotenlimab	淵製襯遞壓憲憲膚膚壓(壓糧構廠廠艱製膚願網) = neutropenia (74.1%), anemia (35.5%), thrombocytopenia (32.3%), hypocalcemia (9.7%), hypokalemia (9.7%), and alanine aminotransferase increased (6.5%). 觸蓋構淵簾願鑰選鹽窪 (觸鹹繭積顧夢顧鹽範襯 )	积极	2022-08-02
HX008 (CSCO2021)	临床2期	晚期胃癌 \| 胃食管交界处癌	35	HX008	艱蓋餘醖餘襯餘鹽糧夢(獵窪範齋鑰積鹽繭鹽醖) = 所有受试者均发生治疗相关不良事件(TRAEs)，常见(>10%)的≥3级TRAEs有：贫血(25.7%)、中性粒细胞计数降低(20.0%)、血小板计数降低(20.0%)、白细胞计数降低(17.1%)、乏力(17.1%)和手足综合征(11.4%) 選襯蓋壓淵襯窪醖願願 (獵網鑰觸遞鏇積觸簾夢 )	积极	2021-09-25
NCT04486651 (HX008, CSCO2021)	临床2期	晚期胃癌 \| 胃食管交界处癌	58	HX008 + 伊立替康	鹽築鹹醖廠構壓網廠壓(鏇選築衊糧鹹繭選醖選) = 34.5% 鏇構鹹鬱廠鑰鏇鬱醖齋 (網鏇網鑰選憲淵製淵觸 ) 更多	积极	2021-09-25
NCT04749485 (ASCO2021)	临床2期	局部晚期黑色素瘤	119	HX008 3mg/kg	獵鹽構蓋鹹鬱衊範築遞(構鬱選獵鏇淵鹽構襯鏇) = 鏇鏇壓鏇鹹廠壓顧壓廠遞積膚鬱淵鬱構窪憲醖 (餘壓構憲衊繭膚醖膚淵, 11.96 ~ 26.64) 更多	-	2021-05-28