Pembrolizumab

9月13~17日，2024年欧洲肿瘤内科学会(ESMO)年会于西班牙巴塞罗那正式召开，此次会议汇聚了全球肿瘤领域的前沿研究进展。四川科伦博泰生物医药股份有限公司(以下简称“科伦博泰”，6990.HK)核心产品TROP2 ADC芦康沙妥珠单抗(sac-TMT，前称SKB264/MK2870)的多项临床研究成果于大会上重磅公布。 口头报告：CC 当地时间9月15日，复旦大学附属肿瘤医院的吴小华教授代表研究团队在oral环节中报告了芦康沙妥珠单抗(sac-TMT)联合帕博利珠单抗（可瑞达®）用于复发或转移性宫颈癌(CC)患者的疗效及安全性临床研究成果。 2024 ESMO现场：吴小华教授进行口头报告 在含铂双药化疗中或之后出现疾病进展且接受过不超过2种针对复发或转移性（R/M）疾病系统治疗（允许使用PD-(L)1抑制剂治疗）的R/M CC患者入组并于安全导入期接受每2周一次3或5 mg/kg剂量的芦康沙妥珠单抗联合每6周一次400 mg剂量的帕博利珠单抗治疗评估，并在剂量拓展阶段探索到视为良好耐受的剂量。38名患者中位随访时间为6.2个月。ORR为57.9% ，其中3例完全缓解。在接受抗PD-1疗法的患者中亦观察到缓解（ORR为68.8%，11/16），6个月PFS率为65.7%，6个月DoR率为82.1%。 吴小华教授表示：“宫颈癌是导致女性癌症死亡的第四大原因，免疫治疗 PD-1/PD-(L)1 作为一线或者二线复发的标准治疗，已经在广泛运用，而当这些患者再次复发时，我今天所报告的TROP2 ADC芦康沙妥珠单抗免疫加靶向的探索有潜力填补未被满足的临床需要，为患者带来全新的治疗选择。” 口头报告：EC/OC 2024 ESMO现场：王丹波教授进行口头报告 同日，辽宁省肿瘤医院的王丹波教授代表研究团队在大会妇科肿瘤oral环节中口头报告了TROP2 ADC芦康沙妥珠单抗(sac-TMT)单药治疗晚期子宫内膜癌（EC）和卵巢癌（OC）的II期临床试验成果。在子宫内膜癌队列中，44例患者中位随访时间为7.2个月。52.3%的患者既往接受过二线或以上的治疗，基线相对较差。芦康沙妥珠单抗仍可取得34.1%的客观缓解率（ORR）和75%的疾病控制率（DCR），中位无进展生存期（PFS）则为5.7个月。在卵巢癌队列中，40例患者中位随访时间长达28.2个月，且所有患者均接受过二线或以上治疗，其中87.5%的患者为铂类耐药，芦康沙妥珠单抗单药治疗取得了40%的ORR和75%的DCR，中位PFS为6个月。 王丹波教授表示：“我非常荣幸能在今年的ESMO大会上分享ADC治疗妇科肿瘤的临床研究结果，我国发达城市的子宫内膜癌发病率逐年攀升，未来可能会成为中国女性妇科恶性肿瘤之首。相比之下，卵巢癌最为显著的特征是发病隐匿、晚期发现率高及高死亡率，是长期以来临床医生所面临的治疗难题。后线治疗仍然存在诸多挑战，目前现有的治疗手段有限，亟待探索新的治疗策略。作为我国自主研发的TROP2ADC芦康沙妥珠单抗(sac-TMT)在试验中所展现的疗效数据惊艳，安全性可控性也较强，展现出巨大的治疗潜力，令我感到无比自豪。” 壁报展示 当地时间9月16日，在芦康沙妥珠单抗(sac-TMT)对比化疗用于既往接受过治疗的晚期三阴性乳腺癌(TNBC)患者的3期研究(OptiTROP-Breast01)中，对既往接受过或未接受过 PD-(L)1 抑制剂治疗的患者的探索性分析结果以壁报形式在大会现场公布。 OptiTROP-Breast01研究是一项多中心、随机对照、开放标签、III期临床研究，由中国医学科学院肿瘤医院徐兵河院士和江苏省人民医院殷咏梅教授共同牵头，旨在评估sac-TMT与TPC在既往接受或未接受过PD-（L）1抑制剂治疗的局部晚期或转移性TNBC患者中的疗效和安全性。与接受TPC（艾立布林、长春瑞滨、卡培他滨或吉西他滨）治疗的患者相比，接受sac-TMT治疗的患者ORR获益更高，无论患者是否曾接受过PD-（L）1抑制剂治疗。在既往接受过PD-（L）1抑制剂治疗的患者亚组中，sac-TMT组的中位PFS为5.6个月，TPC组为2.7个月，在既往未接受过PD-（L）1抑制剂治疗的患者亚组中，sac-TMT组与TPC组的中位PFS分别为7.2个月和2.3个月在安全性方面，sac-TMT组与化疗组整体相仿，不良反应可控。OptiTROP-Breast01研究中期数据分析显示，与化疗相比，接受sac-TMT治疗的患者在无进展生存期（PFS）和总生存期（OS）方面均获得统计学和临床意义的改善。 科伦博泰将继续加速候选药物的研发及临床进度，提升一体化药物开发能力，同时致力于优化OptiDCTM研发平台以支持创新药物的研发,加强建设商业化能力。始终致力于解决中国乃至全球未满足的医疗需求，以为全球患者提供临床价值显著且性价比优异的中国ADC创新药为首要目标。 关于科伦博泰 四川科伦博泰生物医药股份有限公司（简称“科伦博泰生物”，股票代码：6990.HK）是科伦药业控股子公司，专注于生物技术药物及创新小分子药物的研发、生产、商业化及国际合作。公司围绕全球和中国未满足的临床需求，重点布局肿瘤、自身免疫、炎症和代谢等重大疾病领域，建设国际化药物研发与产业化平台，致力于成为在生物技术药物创新领域国际领先的企业。公司在ADC、单抗、双抗、新靶点创新小分子药物的热点技术领域均已取得重大进展。公司目前拥有30余个重点创新药项目，其中10余个项目正处于临床阶段，4个项目处于NDA阶段，多个临床试验为全球多中心研究，在包括中国和欧美等多个国家同步开展。公司成功构建了享誉国际的ADC开发平台OptiDC™，已有5个ADC或新型ADC项目处于临床研究阶段(其中2个ADC项目处于NDA阶段)，多个项目处于临床前研究阶段。更多信息请访问官网https://kelun-biotech.com/。

Approval based on results from the Phase 3 CCTG IND.227/KEYNOTE-483 trial, in which KEYTRUDA plus chemotherapy demonstrated a statistically significant improvement in overall survival versus chemotherapy alone Approval marks the first indication for KEYTRUDA in MPM in the U.S. RAHWAY, NJ, USA I September 18, 2024 I Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with pemetrexed and platinum chemotherapy, for the first-line treatment of adult patients with unresectable advanced or metastatic malignant pleural mesothelioma (MPM). The approval is based on data from the pivotal Phase 2/3 IND.227/KEYNOTE-483 trial. In IND.227/KEYNOTE-483, KEYTRUDA plus chemotherapy demonstrated a statistically significant improvement in overall survival (OS), reducing the risk of death by 21% (HR=0.79 [95% CI, 0.64-0.98]; p=0.0162) compared to chemotherapy alone at the trial’s pre-specified final analysis. Median OS was 17.3 months (95% CI, 14.4-21.3) for KEYTRUDA plus chemotherapy versus 16.1 months (95% CI, 13.1-18.2) for chemotherapy alone. KEYTRUDA plus chemotherapy also significantly improved progression-free survival (PFS) versus chemotherapy alone (HR=0.80 [95% CI, 0.65-0.99], p=0.0194; median PFS 7.1 months [95% CI, 6.9-8.1] versus 7.1 months [95% CI, 6.8-7.7], respectively). Overall response rate (ORR) was significantly higher for KEYTRUDA plus chemotherapy versus chemotherapy alone (52% [95% CI, 45.5-59.0] versus 29% [95% CI, 23.0-35.4], respectively; p<0.00001). Adverse reactions occurring in patients with MPM were generally similar to those in other patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, other transplant (including corneal graft) rejection, and complications of allogeneic hematopoietic stem cell transplantation. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of KEYTRUDA. Based on the severity of the adverse reaction, KEYTRUDA should be withheld or permanently discontinued and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. For more information, see “Selected Important Safety Information” below. “We’re pleased to offer a new first-line treatment option for adult patients with unresectable advanced or metastatic malignant pleural mesothelioma, a disease where prognoses are generally poor,” said Dr. Gregory Lubiniecki, vice president, oncology clinical research, Merck Research Laboratories. “This milestone underscores our commitment to advancing research for patients with difficult-to-treat tumors.” Study design and additional data supporting the approval IND.227/KEYNOTE-483 is a multicenter, randomized, open-label, active-controlled Phase 2/3 trial (ClinicalTrials.gov, NCT02784171 ) sponsored and conducted by CCTG in collaboration with National Cancer Institute of Naples (NCIN) and Intergroupe Francophone de Cancérologie Thoracique (IFCT). Merck provided KEYTRUDA and support for the trial, which investigated the efficacy and safety of KEYTRUDA in combination with pemetrexed and platinum chemotherapy. The Phase 3 component of the trial enrolled 440 patients with unresectable advanced or metastatic MPM and no prior systemic therapy for advanced/metastatic disease, regardless of tumor PD-L1 expression. Patients with autoimmune disease that required systemic therapy within three years of treatment or a medical condition that required immunosuppression were ineligible. Patients were randomized (1:1) to one of the following treatment arms; all study medications were administered via intravenous infusion: Treatment with KEYTRUDA continued until disease progression as determined by the investigator according to modified RECIST 1.1 for mesothelioma (mRECIST), unacceptable toxicity, or a maximum of 24 months. Assessment of tumor status was performed every six weeks for 18 weeks, followed by every 12 weeks thereafter. The main efficacy outcome measure was OS. Additional efficacy outcome measures were PFS, ORR, and duration of response (DoR), as assessed by blinded independent central review (BICR) according to mRECIST. The trial demonstrated a statistically significant improvement in OS, PFS, and ORR in patients randomized to KEYTRUDA in combination with chemotherapy compared with patients randomized to chemotherapy alone. About malignant mesothelioma Malignant mesothelioma is a type of cancer that starts in the linings of certain parts of the body, including the chest, abdomen, heart and testicles. Worldwide, it is estimated there were more than 30,000 new cases of mesothelioma diagnosed and more than 25,000 deaths from the disease in 2022. Pleural mesothelioma, which develops in the lining of the lungs, is the most common form of malignant mesothelioma, accounting for about 75% of all cases. Malignant pleural mesothelioma can progress rapidly, and the five-year survival rate for all stages for cases diagnosed in the U.S. from 2014-2020 was 12.8%. About KEYTRUDA ® (pembrolizumab) injection, 100 mg KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD- L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells. Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers. Selected KEYTRUDA ® (pembrolizumab) Indications in the U.S. Malignant Pleural Mesothelioma KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic malignant pleural mesothelioma (MPM). Melanoma KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma. KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with Stage IIB, IIC, or III melanoma following complete resection. Non-Small Cell Lung Cancer KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations. KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC. KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [Tumor Proportion Score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is: KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA. KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery. KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC. Head and Neck Squamous Cell Cancer KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC). KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test. KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy. Classical Hodgkin Lymphoma KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL). KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy. Primary Mediastinal Large B-Cell Lymphoma KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy. Urothelial Cancer KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer. KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma: KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy. Microsatellite Instability-High or Mismatch Repair Deficient Cancer KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test. Gastric Cancer KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval of this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma. Esophageal Cancer KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either: Cervical Cancer KEYTRUDA, in combination with chemoradiotherapy (CRT), is indicated for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer. KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. Hepatocellular Carcinoma KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen. Biliary Tract Cancer KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC). Merkel Cell Carcinoma KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). Renal Cell Carcinoma KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. Endometrial Carcinoma KEYTRUDA, in combination with carboplatin and paclitaxel, followed by KEYTRUDA as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma. KEYTRUDA, as a single agent, is indicated for the treatment of adult patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation. Tumor Mutational Burden-High Cancer KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established. Cutaneous Squamous Cell Carcinoma KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation. Triple-Negative Breast Cancer KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery. KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test. About the Merck Access Program for KEYTRUDA At Merck, we are committed to supporting accessibility to our cancer medicines. Merck provides multiple programs to help appropriate patients who are prescribed KEYTRUDA have access to our anti-PD-1 therapy. The Merck Access Program provides reimbursement support for patients receiving KEYTRUDA, including information to help with out-of-pocket costs and co-pay assistance for eligible patients. More information is available by calling 855-257-3932 or visiting www.merckaccessprogram-keytruda.com . About Merck’s Patient Support Program for KEYTRUDA Merck is committed to helping provide patients and their caregivers support throughout their treatment with KEYTRUDA. The KEY+YOU Patient Support Program provides a range of resources and support. For further information and to sign up, eligible patients may call 85-KEYTRUDA (855-398-7832) or visit www.keytruda.com . Merck’s focus on cancer Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit https://www.merck.com/research/oncology . About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . SOURCE: Merck