A Phase II Open Label, Randomized Study Testing the Efficacy of Retifanlimab in Combination with Bevacizumab and Hypofractionated Radiotherapy in Patients with Recurrent GBM

This phase II trial tests how well retifanlimab with bevacizumab and hypofractionated radiotherapy, compared to bevacizumab and hypofractionated radiotherapy alone, works in treating patients with glioblastoma that has come back after a period of improvement (recurrent). A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as retifanlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving retifanlimab with bevacizumab and hypofractionated radiotherapy may work better in treating patients with recurrent glioblastoma than bevacizumab and hypofractionated radiotherapy alone.

开始日期2024-09-30

申办/合作机构

National Cancer Institute

NCT06290622 / Withdrawn临床1期IIT

PD-1, LAG-3 and TIM-3 Checkpoint Blockade in DLBCL Post Chimeric Antigen Receptor T-cEll Therapy fAilUre (PLATEAU Study)

This study is investigating the optimal dose and the advantage in combining investigational immunotherapy drugs known as Retifanlimab, INCAGN02385 and INCAGN02390 to improve the responses to CAR T-cell therapy. Additionally, the study will investigate that triple checkpoint blockade of PD-1, TIM-3 and LAG-3 molecules will overcome CAR T-cell therapy resistance in patients with suboptimal responses.

开始日期2024-08-30

申办/合作机构

The University of Alabama at Birmingham

NCT06389799 / Recruiting临床2期IIT

A Phase 2, Open Label Study of PEmigatinib and REtifanlimab in Advanced Dedifferentiated LIposarcoma

Dedifferentiated liposarcomas (DDLPS) are aggressive soft tissue sarcomas with no effective medical treatment options.
Immunotherapy with checkpoint inhibitors, so-called PD-1 inhibitors, have shown some effect in DDLPS in previous studies. Effect of immunotherapy can be improved by combining it with other types of tumor drugs. Medicines that inhibit signaling via the FGF receptor, so-called FGFR inhibitors, have shown a tumor-slowing effect in DDLPS in early studies. FGFR inhibitors can also induce changes that make the tumor more available to treatment with immunotherapy.
The study aims to investigate whether the combination of an FGFR inhibitor, pemigatinib, with a PD-1 inhibitor, retifanlimab can provide a tumor-slowing effect in patients with advanced DDLPS who have progressed on first-line treatment.

开始日期2024-06-20

申办/合作机构

Lund University Hospital

100 项与瑞弗利单抗相关的临床结果

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100 项与瑞弗利单抗相关的专利（医药）

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项与瑞弗利单抗相关的文献（医药）

2024-12-31·mAbs

Antibodies to watch in 2024

Article

作者: Crescioli, Silvia ; Kaplon, Hélène ; Wang, Lin ; Reichert, Janice M. ; Visweswaraiah, Jyothsna ; Chenoweth, Alicia

The 'Antibodies to Watch' article series provides an annual summary of commercially sponsored monoclonal antibody therapeutics currently in late-stage clinical development, regulatory review, and those recently granted a first approval in any country. In this installment, we discuss key details for 16 antibody therapeutics granted a first approval in 2023, as of November 17 (lecanemab (Leqembi), rozanolixizumab (RYSTIGGO), pozelimab (VEOPOZ), mirikizumab (Omvoh), talquetamab (Talvey), elranatamab (Elrexfio), epcoritamab (EPKINLY), glofitamab (COLUMVI), retifanlimab (Zynyz), concizumab (Alhemo), lebrikizumab (EBGLYSS), tafolecimab (SINTBILO), narlumosbart (Jinlitai), zuberitamab (Enrexib), adebrelimab (Arelili), and divozilimab (Ivlizi)). We briefly review 26 product candidates for which marketing applications are under consideration in at least one country or region, and 23 investigational antibody therapeutics that are forecast to enter regulatory review by the end of 2024 based on company disclosures. These nearly 50 product candidates include numerous innovative bispecific antibodies, such as odronextamab, ivonescimab, linvoseltamab, zenocutuzumab, and erfonrilimab, and antibody-drug conjugates, such as trastuzumab botidotin, patritumab deruxtecan, datopotamab deruxtecan, and MRG002, as well as a mixture of two immunocytokines (bifikafusp alfa and onfekafusp alfa). We also discuss clinical phase transition and overall approval success rates for antibody therapeutics, which are crucial to the biopharmaceutical industry because these rates inform decisions about resource allocation. Our analyses indicate that these molecules have approval success rates in the range of 14-32%, with higher rates associated with antibodies developed for non-cancer indications. Overall, our data suggest that antibody therapeutic development efforts by the biopharmaceutical industry are robust and increasingly successful.

2024-10-01·Surgical Oncology Clinics of North America

Updates in the Management of Advanced Nonmelanoma Skin Cancer

Review

作者: Yan, Flora ; Schmalbach, Cecelia E ; Schmalbach, Cecelia E.

Basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC) comprise the majority of nonmelanoma skin cancers. Advances have been made in treatment. Sentinel node biopsy should be considered for locally advanced, clinically node-negative cSCCs and MCCs. BCC patients failing traditional surgery and/or radiation are candidates for systemic hedgehog inhibitor therapy. Immune checkpoint inhibitor treatment is available for patients who failed traditional treatment with surgery and/or radiation or who are not candidates for these modalities. Specifically, cemiplimab is approved for advanced BCC; cemiplimab and pembrolizumab for advanced cSCC; and avelumab, pembrolizumab, and retifanlimab-dlwr for recurrent/metastatic MCC.

2024-07-01·GYNECOLOGIC ONCOLOGY

Antitumor activity and safety of the PD-1 inhibitor retifanlimab in patients with recurrent microsatellite instability-high or deficient mismatch repair endometrial cancer: Final safety and efficacy results from cohort H of the POD1UM-101 phase I study

Article

作者: Tian, Chuan ; Cornfeld, Mark ; Gladieff, Laurence ; Pautier, Patricia ; Bowman, Jill ; Van Gorp, Toon ; Lorusso, Domenica ; Gennigens, Christine ; Berton, Dominique ; Kryzhanivska, Anna

OBJECTIVE:

Retifanlimab is a humanized immunoglobulin G4 monoclonal antibody against programmed death 1 being investigated in several solid tumor types. We report final results from patients with recurrent microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) endometrial cancer treated with retifanlimab in a POD1UM-101 expansion cohort.

METHODS:

Eligible patients (≥18 years; histologically proven/unresectable/recurrent, MSI-H/dMMR endometrial cancer; checkpoint inhibitor naive) received retifanlimab 500 mg intravenously every 4 weeks for ≤2 years. Primary endpoint was safety/tolerability.

RESULTS:

At data cutoff (May 17, 2023), 76 patients had received at least one retifanlimab dose. Median (range) age was 67 (49-88) years; 88.2% of patients had recurrent metastatic disease and 80.3% had visceral metastases. Seventy-five patients (98.7%) had received at least one prior systemic therapy. Median retifanlimab exposure was 10.0 (0.03-25.9) months; 23 patients completed treatment. 38 patients (50.0%) had grade ≥3 treatment-emergent adverse events (TEAEs), most commonly anemia (n = 10 [13.2%]). 63 patients (82.9%) had treatment-related AEs (TRAEs; grade ≥3, n = 14 [18.4%]); most common was fatigue (n = 14 [18.4%]). Two patients had TEAEs that led to death; no TRAEs were fatal. 39 patients had objective responses (51.3%; 95% CI, 39.6-63.0%); 19 patients (25.0%) had complete response and 20 (26.3%) had partial response. Median progression-free survival was 12.2 months; 30 patients (76.9%) had duration of response (DOR) ≥12 months. Median DOR was not reached after median follow-up time of 26.0 months.

CONCLUSIONS:

Retifanlimab was generally well tolerated and demonstrated encouraging anti-tumor activity in patients with pre-treated recurrent MSI-H/dMMR endometrial cancer.

113

项与瑞弗利单抗相关的新闻（医药）

2024-10-30

·GlobeNewswire-Health Care

MacroGenics Announces Leadership Transition

Scott Koenig, M.D., Ph.D., to step down as President and CEOBoard to initiate search process to identify new CEO ROCKVILLE, MD, Oct. 30, 2024 (GLOBE NEWSWIRE) -- MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative antibody-based therapeutics for the treatment of cancer, today announced that Scott Koenig, M.D., Ph.D., intends to step down as President and Chief Executive Officer early next year. The Company’s Board of Directors has retained Heidrick & Struggles to lead a search process to identify its next Chief Executive Officer and has established a special committee of the Board to oversee the transition process. William Heiden, Chairman of the Board of Directors said, “Scott was a co-founder of MacroGenics twenty-four years ago and the Company has achieved many milestones under his leadership – including several partnered or company-owned FDA approved monoclonal antibody therapeutics developed by the company. On behalf of the Board, I want to thank Scott for his incredible dedication to the Company’s mission of discovering and developing novel therapeutics to improve patient care.” Mr. Heiden continued, “Today, MacroGenics has several innovative antibody-based therapeutics in development for the treatment of cancer, as well as significant alliances with leading pharmaceutical and biotechnology companies to develop and commercialize novel therapeutics. The Company today has a broad portfolio of promising assets and a strong balance sheet, and the Board and Scott agreed that this is the right time to transition to our next phase of leadership. We look forward to continuing to benefit from his perspectives as an advisor and shareholder.” “I am proud of our many achievements since our founding in 2000, in which we built a fully integrated, science-focused biotechnology company and have been successful in discovering, developing, manufacturing, and commercializing novel immunotherapeutics derived from our proprietary Fc-engineered antibody, bi-specific DART molecule, and antibody drug conjugate (ADC) technologies,” said Dr. Koenig. “Since the company’s IPO in 2013, we were able to fund a significant part of the development portfolio through the achievement of over $1 billion of non-dilutive capital via partnerships. Thanks to the incredible passion and dedication of the people at MacroGenics, three novel therapeutics from our pipeline advanced to approval, including MARGENZA® and ZYNYZ® to treat patients with cancer, and TZIELD® for individuals with early-stage Type 1 diabetes, and we have advanced a rich portfolio of clinical and preclinical molecules in development. I am confident that MacroGenics is well positioned in its current mission to address the significant unmet medical needs of patients with cancer. I look forward to continuing to support the Company in its work to achieve its key strategic objectives and create value for all our stakeholders.” About MacroGenics, Inc. MacroGenics is a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer. The Company generates its pipeline of product candidates primarily from its proprietary suite of next-generation antibody-based technology platforms, which have applicability across broad therapeutic domains. The combination of MacroGenics' technology platforms and protein engineering expertise has allowed the Company to generate promising product candidates and enter into several strategic collaborations with global pharmaceutical and biotechnology companies. For more information, please see the Company's website at www.macrogenics.com. MacroGenics, the MacroGenics logo and MARGENZA are trademarks or registered trademarks of MacroGenics, Inc. Cautionary Note on Forward-Looking Statements Any statements in this press release about future expectations, plans and prospects for MacroGenics (“Company”), including statements about the Company’s strategy, future operations, clinical development of and regulatory plans for the Company’s therapeutic candidates, expected timing of the release of final safety and efficacy data, including mature median rPFS and other statements containing the words “subject to”, "believe", “anticipate”, “plan”, “expect”, “intend”, “estimate”, “potential,” “project”, “may”, “will”, “should”, “would”, “could”, “can”, the negatives thereof, variations thereon and similar expressions, or by discussions of strategy constitute forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: risks that TZIELD, vobramitamab duocarmazine, lorigerlimab, ZYNYZ, MARGENZA or any other product candidate’s revenue, expenses and costs may not be as expected, risks relating to TZIELD, vobramitamab duocarmazine, lorigerlimab, ZYNYZ, MARGENZA or any other product candidate’s market acceptance, competition, reimbursement and regulatory actions; future data updates, especially timing and results of mature median radiographic progression-free survival, other efficacy and safety data with respect to vobramitamab duocarmazine; our ability to provide manufacturing services to our customers; the uncertainties inherent in the initiation and enrollment of future clinical trials; the availability of financing to fund the internal development of our product candidates; expectations of expanding ongoing clinical trials; availability and timing of data from ongoing clinical trials; expectations for the timing and steps required in the regulatory review process; expectations for regulatory approvals; expectations of future milestone payments; the impact of competitive products; our ability to enter into agreements with strategic partners and other matters that could affect the availability or commercial potential of the Company's product candidates; business, economic or political disruptions due to catastrophes or other events, including natural disasters, terrorist attacks, civil unrest and actual or threatened armed conflict, or public health crises; costs of litigation and the failure to successfully defend lawsuits and other claims against us; and other risks described in the Company's filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company's views only as of the date hereof. The Company anticipates that subsequent events and developments will cause the Company's views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so, except as may be required by law. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date hereof. ###

高管变更IPO抗体药物偶联物

2024-10-25

·ioncology

ESMO ASIA 2024丨一文了解胸部肿瘤口头报告

点击蓝字关注我们 2024年欧洲肿瘤内科学会亚洲年会（ESMO Asia Congress 2024）将于当地时间12月6日~8日在新加坡召开。ESMO ASIA是亚太地区讨论肿瘤学领域重磅突破的领先平台，近日在官方网站正式公布本次大会的摘要题目及作者信息。肿瘤瞭望小编带您先睹为快，一览胸部肿瘤领域入选优选口头报告（Proffered Paper）和微型口头报告（Mini Oral）的临床研究。 1 优选口头报告（Proffered Paper）摘要号：LBA8 英文标题：Phase II trial of atezolizumab plus carboplatin and paclitaxel in patients with metastatic or recurrent thymic carcinoma: Marble study 中文标题：阿替利珠单抗+卡铂/紫杉醇治疗转移性或复发性胸腺癌的II期临床试验：Marble研究讲者：Tomoyasu Mimori (日本) 摘要号：625O 英文标题：Efficacy and safety of Lucitanib (AL3810) in second or subsequent-line treatment of advanced recurrent or metastatic thymic carcinoma: a randomized, double-blind, placebo-controlled multicenter phase II trial 中文标题：Lucitanib在晚期复发或转移性胸腺癌二线或后续治疗中的疗效和安全性：一项随机、双盲、安慰剂对照的多中心II期试验讲者：方文涛（上海交通大学医学院附属胸科医院）摘要号：LBA5 英文标题：Zongertinib in patients with HER2-mutant NSCLC: Updated analysis of Beamion LUNG-1 中文标题：Zongertinib治疗HER2突变型NSCLC患者：Beamion LUNG-1的最新分析讲者：Noboru Yamamoto (日本) 摘要号：LBA6 英文标题：PACIFIC-5: A phase 3 study of consolidation durvalumab (D) in patients (pts) with unresectable stage III NSCLC and no progression after concurrent or sequential chemoradiotherapy (cCRT or sCRT) 中文标题：PACIFIC-5：针对同步或序贯放化疗（cCRT或sCRT）后未出现进展不可切除III期NSCLC患者进行巩固性度伐利尤单抗治疗的III期研究讲者：吴一龙（广东省人民医院）摘要号：LBA7 英文标题：Efficacy and safety of datopotamab deruxtecan (Dato-DXd) in patients (pts) with previously-treated EGFR-mutated advanced non-small cell lung cancer (NSCLC): a pooled analysis of TROPION-Lung01 and TROPION-Lung05 中文标题：Dato-DXd对既往接受过治疗的EGFR突变晚期非小细胞肺癌患者的疗效和安全性：TROPION-Lung01和TROPION-Lung05的汇总分析讲者：Myung-Ju Ahn (韩国) 2 微型口头报告（Mini Oral）摘要号：626MO 英文标题：Tarlatamab in previously treated small cell lung cancer (SCLC): Subgroup analysis of patients from the Asia region in the phase 2 DeLLphi-301 study 中文标题：Tarlatamab治疗既往接受过治疗的小细胞肺癌：II期DeLLphi-301研究中亚洲地区患者的亚组分析讲者：Hiroaki Akamatsu (日本) 摘要号：627MO 英文标题：POD1UM-304: Phase 3 Study of Retifanlimab Plus Platinum-Based Chemotherapy (Chemo) as First-Line (1L) Therapy For Nonsquamous or Squamous Metastatic Non–Small Cell Lung Cancer (mNSCLC) 中文标题：POD1UM-304：Retifanlimab+铂类化疗作为非鳞或鳞状转移性非小细胞肺癌一线疗法的III期研究讲者：陆舜(上海交通大学医学院附属胸科医院) 摘要号：614MO 英文标题：A Phase Ⅱ Study of Becotatug (JMT101) in Combination with Osimertinib (Osi) in Patients (pts) with classical EGFR-mutated Non-small Cell Lung Cancer (NSCLC) (BOOSTER Study) 中文标题：Becotatug联合奥希替尼治疗经典型EGFR突变非小细胞肺癌患者的Ⅱ期BOOSTER临床研究讲者：张力(中山大学肿瘤防治中心) 摘要号：630MO 英文标题：First-line (1L) osimertinib (osi) ± platinum-pemetrexed chemotherapy (CTx) for EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC): FLAURA2 Asian cohort 中文标题：一线奥希替尼±铂类-培美曲塞化疗治疗EGFR突变晚期非小细胞肺癌：FLAURA2亚洲队列讲者：James Chih-Hsin Yang (中国台湾) 摘要号：628MO 英文标题：Comparing Subcutaneous vs Intravenous Amivantamab with Lazertinib in EGFR-Mutated Advanced NSCLC: Analysis of Asian Patients From PALOMA-3 中文标题：比较皮下注射vs静脉注射Amivantamab联合Lazertinib治疗EGFR突变晚期NSCLC：对PALOMA-3亚洲患者的分析讲者：Se-Hoon Lee (韩国) 摘要号：629MO 英文标题：ALESIA 7-year update: alectinib vs crizotinib in Asian patients (pts) with treatment-naïve advanced ALK+ non-small cell lung cancer (NSCLC) 中文标题：ALESIA研究7年随访更新：阿来替尼vs克唑替尼在未经治疗的晚期ALK+非小细胞肺癌亚洲患者中的疗效对比讲者：周彩存(上海市东方医院) （来源：《肿瘤瞭望》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

临床2期临床结果临床3期

2024-10-05

·CPHI制药在线

如日中天的PD-1抑制剂行至水穷处了吗？

关注并星标CPHI制药在线在肿瘤学领域，Opdivo和Keytruda作为PD-1抑制剂的免疫治疗核心药物，已经为多种癌症患者带来了显著的生存获益。Keytruda和Opdivo凭借其卓越的疗效和广泛的适应症，已在全球肿瘤学市场中占据了极为重要地位。它们的市场表现不仅巩固了其作为免疫治疗领军药物的崇高地位，也证明了PD-1抑制剂在癌症治疗中的核心作用。在2024年第二季度，Keytruda和Opdivo分别收获了72.7亿23.9亿美元的销售业绩，排在肿瘤学药物的第一和第三位（排在第二的是强生/Genmab的多发性骨髓瘤药物Darzalex，28.8亿美元）。图1 显示了获得FDA批准上市的10款PD-1抑制剂肿瘤学产品2023年销售额与适应症数量。图1. 获得FDA批准的PD-1抑制剂肿瘤学药物2023年销售额及获批适应症对比。（注：Loqtorzi与Tevimbra分别于2022和2023年获批，无2023年销售额数据）尽管PD-1抑制剂依然是肿瘤免疫疗法的重要支柱，但随着科学研究的不断进展，一系列新型药物正在为患者提供更多的治疗选择。这些创新疗法展现出独特的机制和潜力，与PD-1抑制剂形成互补，为癌症治疗打开了新的大门，也让我们看到了未来肿瘤治疗更加多样化的可能性。 1.超越PD-1抑制剂的新型疗法检查点抑制剂已经彻底改变了癌症治疗，但依然会面临无能无力的案例和患者。有些患者接受了PD-1抑制剂药物，但病情仍然进展。对于PD-1身后留下的这些空白，Replimune公司相信，他们的癌症疫苗RP1（vusolimogene oderparepvec）有望成为对PD-1抑制剂没有反应的黑色素瘤患者的首选方案，他们发布的IGNYTE试验数据也令人印象深刻。 RP1 是一种基于 HSV-1 （单纯疱疹病毒1）基因改造的溶瘤免疫疗法。RP1可以选择性地感染并杀死癌细胞，而不会对正常细胞造成严重损害。在感染癌细胞后，RP1会复制并破坏这些细胞，释放出肿瘤抗原。RP1不仅直接杀死癌细胞，还通过释放的肿瘤抗原激活患者的免疫系统，从而产生对肿瘤的全身性免疫反应。这种免疫激活类似于疫苗作用，帮助身体识别并攻击其他癌细胞。除此之外，RP1还表达 GM-CSF（细胞-巨噬细胞集落刺激因子）和融合蛋白。GM-CSF可以刺激免疫系统中的抗肿瘤细胞（如树突状细胞和巨噬细胞），增强它们对癌细胞的识别和杀伤能力。通过增强对肿瘤抗原的展示，GM-CSF使得癌细胞死亡更具免疫原性，有助于激发更强的免疫反应。GM-CSF的表达还可以增强局部和全身的免疫反应，促使免疫系统识别和攻击远处的肿瘤病灶。不仅如此，RP1表达的编码的 GALV-GP R 蛋白可增强病毒的肿瘤杀伤能力并增加免疫原性细胞死亡。也就是说，RP1不仅利用HSV-1的溶瘤特性直接攻击癌细胞，还通过GM-CSF的免疫增强作用激发全面的免疫反应，从而提高对癌症的治疗效果。 RP1疫苗的临床数据来自IGNYTE实体瘤试验中的140名黑色素瘤患者。患者在接受至少两个月的抗PD-1治疗（可能合并抗CTLA-4药物）后病情恶化。大多数患者接受过一线（45.7%）或两线（18.6%）治疗。56.4%的患者PD-L1表达低于1%，65.7%的患者对PD-1药物存在初始耐药性，这种现象可能真正反映了现实世界中的后期黑色素瘤患者群体。 Replimune在6月披露，RP1联合BMS的PD-1药物Opdivo（nivolumab）在使用一年后取得了33.6%的总体应答率。这表明这种联合疗法已经略微优于这个领域已获批的创新疗法，Iovance Biotherapeutics公司的肿瘤浸润淋巴细胞（TIL）疗法Amtagvi（lifileucel）。Amtagvi在II期C-144-01试验中达到了32.9%的总体应答率 (根据RECIST 1.1)，促使FDA于2023年2月授予其治疗PD-1疗法失败的黑色素瘤的加速批准。Amtagvi因此成为在PD-1疗法失效后的黑色素瘤治疗中一种重要的替代方案，专为应对对现有免疫检查点抑制剂产生耐药的晚期患者群体。如今RP1联合Opdivo给出了优于Amtagvi的数据，可谓在PD-1抑制剂的基础上迈出的重要一步，也可被视为PD-1联合疗法的重要突破。在安全性方面，RP1疗法总体耐受性良好，只有12.8%的患者出现了3-4级不良事件。4级不良事件包括各一例的脂肪酶升高、细胞因子释放综合征、心肌炎、肝细胞溶解和脾破裂。未报告死亡病例，这一点再次让RP1优于Amtagvi，后者带有一项治疗相关死亡的黑框警告，同时伴有长期的严重血细胞减少症、严重感染以及心肺和肾功能障碍。 Replimune计划在今年年底递交RP1的BLA申请，争取FDA的加速批准。与此同时，他们已经展开了一项黑色素瘤试验IGNYTE-3的验证性试验的患者招募，并于8月13日为第一名受试者进行了注射，进一步评估 RP1 和Opdivo的联合疗法对于PD-1抑制剂和CTLA-4抑制剂治疗后病情进展的晚期黑色素瘤患者的作用。 2.源于PD-1但超越PD-1的双特异性抗体不同于PD-1的联合疗法，PD-1抑制剂在双特异性抗体的道路上也展现出了突破樊笼的趋势。Summit Therapeutics和Akeso Inc.的双特异性抗体ivonescimab的二期临床试验中取得了显著成果，而且直接向药王Keytruda发起了挑战。 Ivonescimab这种双特异性抗体同时靶向PD-1和VEGF，在头颈癌、结直肠癌和乳腺癌患者中表现出了强大的疗效。2024年9月16日，Akeso在西班牙巴塞罗那举行的欧洲临床肿瘤学会（ESMO）年会上展示了ivonescimab的二期研究数据，涉及ivonescimab与化疗联合使用，或与CD47抗体ligufalimab联合使用的效果，针对微卫星稳定型结直肠癌（MSS CRC）、复发/转移性头颈部鳞状细胞癌（HNSCC）和三阴性乳腺癌（TNBC），且均为一线治疗。 Ivonescimab更令人侧目的是在其III期HARMONi-2研究中，ivonescimab显示出了优于Keytruda单药的明显优势。这项中国的临床研究显示，ivonescimab在PD-L1阳性患者中将疾病进展或死亡的风险降低了49%，实现了Keytruda竞争对手在治疗晚期非小细胞肺癌的首线治疗中的首次超越。HARMONi-2研究显示ivonescimab在四个主要亚型中，包括PD-L1低、PD-L1高、鳞状和非鳞状患者中都优于Keytruda。在近九个月的中位随访后，ivonescimab 治疗的患者的中位无进展生存期为 11.14 个月，而 Keytruda 组仅为 5.82 个月。与 Keytruda 相比，ivonescimab 将疾病进展或死亡的风险降低了近 50%，这一效果在统计上具有显著意义，p 值小于 0.0001。这一发现也在各种亚组分析中得到了验证，包括高低 PD-L1 蛋白表达水平的患者，以及鳞状和非鳞状疾病组。在关键的次要终点方面，ivonescimab 同样超越了 Keytruda。Ivonescimab 治疗的患者整体反应率为 50%，而 Keytruda 组为 38.5%。疾病控制率在这两个治疗组分别为 89.9% 和 70.5%。 Ivonescimab的挑战在于Summit需要将这些数据结果与全球研究结果相匹配。公司已计划开展全球III期研究，以获得美国、欧洲及其他关键国际市场的批准。考虑到 Keytruda 预计在 2028 年面临专利悬崖，默沙东认为ivonescimab 对 Keytruda的影响可能不会太大。 Ivonescimab已经获得在中国的首个批准，作为EGFR突变NSCLC的二线治疗。它的HARMONi-3研究将ivonescimab与化疗联合使用，并与Keytruda加化疗进行头对头比较，但仅限于鳞状NSCLC患者，这些患者占总数的25-30%，这是因为他们相对于非鳞状患者具有更大的未满足需求。在公布结果之后，分析师上调了ivonescimab的批准概率，并提高了其销售预测，预计在HNSCC (头颈部鳞状细胞癌) 中的销售峰值可达22亿美元，到2040年所有适应症的总销售峰值为157亿美元。 Ivonescimab在与Keytruda比较时表现出的优异效果，可能会对PD-1免疫检查点抑制剂领域产生深远的影响。Ivonescimab展示了其作为PD-1和VEGF双特异性抗体的潜力，特别是在非小细胞肺癌（NSCLC）中的应用。这种双重作用机制可能使ivonescimab在治疗效果上超越了单一针对PD-1的药物。这一突破表明，单纯的PD-1抑制可能不足以完全发挥免疫系统对抗癌症的能力，在某些情况下，结合其他机制的抑制可能更有效。这可能会推动对现有PD-1抑制剂的改进，或激励开发新的药物，结合不同的靶点以增强治疗效果。 3.PD-1抑制剂的“自我救赎” 作为PD-1抑制剂元老，阿斯利康的Imfinzi（durvalumab）也在近期实现了“自我救赎”，在通往膀胱癌市场的道路上跌倒后重新站起。 2017年，Imfinzi凭借I/II期研究获得了FDA针对局部晚期或转移性尿路上皮癌的首次加速批准，但接下来在2020年的III期验证性试验DANUBE中失败，导致阿斯利康于2021年撤回了针对该适应症的申请。与此同时，竞争对手的检查点抑制剂Keytruda和Opdivo在膀胱癌领域已经抢占了市场，显示了在膀胱癌高风险复发患者的辅助治疗中提高无病生存期的益处。卷土重来的阿斯利康在6月底宣布了Imfinzi的NIAGARA试验的无事件生存期和总体生存期的顶线数据。该研究中，患者在根治性膀胱切除术前接受了Imfinzi与化疗的联合治疗，手术后又接受了Imfinzi作为辅助治疗，与新辅助（即手术前）化疗加手术对比，在约1000名肌肉侵袭性膀胱癌患者中进行研究。阿斯利康在ESMO 24会议上表示，围手术期使用Imfinzi相较于新辅助化疗，在疾病进展、复发、未接受手术或死亡的风险上减少了32%。在关键的次要终点总体生存期方面，相比于新辅助化疗与根治性膀胱切除术的组合，围手术期使用Imfinzi减少了25%的死亡风险。 4.PD-1百尺竿头的自我突破创造出肿瘤学奇迹的PD-1抑制剂还远未到“行至水穷处，坐看云起时”的阶段，仍然有着不少可以开拓创新的领域。阿斯利康的PD-1抑制剂Zynyz（retifanlimab）就在罕见癌症——不可切除的晚期鳞状细胞肛管癌（SCAC）上实现了突破。根据阿斯利康在ESMO 24上公布的第3期POD1UM-303试验结果，Zynyz联合化疗将先前未治疗的不可切除的晚期鳞状细胞肛管癌患者的进展或死亡风险降低了37%，相比单独化疗，Zynyz联合化疗显著改善了患者的生存状况。值得注意的是，2021 年 10 月，Incyte 曾经撤回了Zynyz 用于肛门癌化疗后二线治疗的BLA申请，主要原因是因肿瘤反应率低和一些与疾病进展无关的患者死亡，此番重装上阵也是对这个罕见肿瘤学领域锲而不舍的回报。肛门癌从财务角度看并不是一个大的肿瘤市场。Zynyz的目标患者群体在美国和欧洲每年约有1万个新诊断病例。Incyte计划在年底前向FDA申请Zynyz的批准，使其有望成为首个用于一线肛门癌治疗的PD-1抑制剂。这使得Zynyz在小众适应症中可能会为Incyte带来一些回报。 Zynyz去年通过FDA批准进入市场，用于默克尔细胞癌（另一种罕见的癌症类型）。此外，Incyte还宣布Zynyz在POD1UM-304试验中与化疗联合用于一线非小细胞肺癌（NSCLC）的结果积极。 5.联合疗法，PD-1抑制剂的新天地 PD-1抑制剂通过阻断PD-1/PD-L1通路，恢复T细胞的抗肿瘤活性，已经在多种肿瘤类型中显示出显著疗效。然而，尽管PD-1抑制剂在某些患者中表现出长期的抗肿瘤效果，但许多患者对单药治疗无反应，或者治疗后产生耐药性。因此，研究人员和制药公司越来越多地探索PD-1抑制剂与其他治疗手段的联合疗法，以扩大其适用范围、提高治疗效果并克服耐药性。例如药王Keytruda在2014年首次获批后的第七次FDA批准就开始了联合疗法（2017年，转移性非鳞状非小细胞肺癌患者的一线联合疗法），之后又陆续获得了17项FDA批准的联合疗法，其联合对象包括卡铂和紫杉醇（2024年6月17日，原发性晚期或复发性子宫内膜癌）、放化疗（2024年1月12日，宫颈癌）、Padcev (enfortumab vedotin-ejfv，抗体药物偶联物，2023年12月15日，晚期膀胱癌) 、吉西他滨和顺铂（2023年11月1日，局部晚期不可切除或转移性胆道癌）等。默沙东在ESMO 24上公布的最新Keytruda临床数据同样是联合疗法。在Keytruda的KEYNOTE-A18 III期试验中共招募了1060名新诊断的高危局部晚期宫颈癌女性，接受了Keytruda联合放化疗的治疗。FDA已于今年1月机遇第一次中期分析的结果批准了Keytruda/CRT（放化疗）组合用于III-IVA期宫颈癌女性的治疗，此次公布的是第二次中期分析的数据。数据显示，经过中位随访29.9个月后，Keytruda/CRT组36个月的OS率为82.6%，而单纯CRT组为74.8%。除此之外，默沙东还公布了Keytruda联合放化疗治疗三阴乳腺癌（TNBC）的KEYNOTE-522 III期试验的OS数据。在中位随访75.1个月后，Keytruda方案使患者的死亡风险降低了34%，与安慰剂加化疗并术后维持安慰剂治疗相比，Keytruda组五年OS率为86.6%，而对照组为81.7%。 Keytruda不断开拓联合疗法应用的努力代表着PD-1未来的发展方向，这种趋势主要来自于以下考量： ●增强抗肿瘤反应：联合疗法可以通过多种机制增强免疫系统对癌细胞的攻击。例如，PD-1抑制剂与化疗、放疗或其他靶向药物的联合使用，可以通过刺激肿瘤抗原的释放或改变肿瘤微环境，进一步激活免疫反应。 ●克服免疫逃逸：单独使用PD-1抑制剂时，某些肿瘤会通过多种途径逃避免疫系统的识别或抑制免疫系统的活性。联合其他免疫检查点抑制剂（如CTLA-4抑制剂）或其他类型的免疫疗法（如溶瘤病毒、CAR-T细胞疗法等），可以封锁更多的肿瘤逃逸机制，从而提高免疫系统的抗肿瘤能力。 ●扩大适应症范围：PD-1抑制剂对不同肿瘤的敏感性不同，通过联合其他疗法，可以扩大PD-1抑制剂的适用范围。例如，某些肿瘤对PD-1单药治疗不敏感，但通过联合化疗、放疗或血管生成抑制剂，可以提高对PD-1抑制剂的敏感性。 ●减少耐药性：许多患者在接受PD-1抑制剂治疗后会产生耐药性。通过联合其他治疗手段，能够延缓或预防耐药性的产生。例如，抗血管生成药物与PD-1抑制剂的联合使用可以改变肿瘤微环境，使其更适合T细胞渗透和杀伤，从而克服耐药性。 ●改善疗效和生存期：越来越多的临床试验证明，联合疗法比单药疗法在多个癌种中的疗效更佳。例如，PD-1抑制剂与CTLA-4抑制剂的联合使用，在黑色素瘤、非小细胞肺癌等肿瘤中已显示出显著的生存期延长和病情控制率提高。 PD-1抑制剂与其他疗法的联合为抗肿瘤治疗开辟了新的天地，提供了更多的治疗选择，并有望克服单药治疗的局限性，使更多患者从中获益。这种组合策略在未来肿瘤治疗中将具有重要地位。以Keytruda和Opdivo为代表的PD-1抑制剂在肿瘤免疫治疗领域已经取得了显著成果，成功改变了多种癌症的治疗格局。然而，PD-1疗法的发展潜力依然巨大。首先，PD-1抑制剂的适应症有望进一步扩展，更多癌种和更早期的肿瘤患者可能从中获益。其次，PD-1抑制剂与其他新型疗法的联合使用，如与细胞治疗、肿瘤疫苗或其他免疫检查点抑制剂的联用，有可能提升疗效，克服耐药性。此外，生物标志物的不断优化将帮助更精准地筛选受益患者，提升个体化治疗效果。随着技术和研究的进步，PD-1抑制剂在治疗复杂肿瘤中的作用将更加广泛，未来的发展空间依然广阔。 Ref. Sava, J. RP1 Plus Nivolumab Demonstrates Durable Antitumor Activity in Advanced Melanoma. OncLive. 15. 09. 2024. Cairns, E. ESMO 24: Replimune’s Cancer Vaccine Succeeds In PD-1 Failures. Scrip. 16. 09. 2024. Manalac, T. Summit Declares NSCLC Victory Over Keytruda, Analysts Advise Caution With China-Only Data. Biospace. 09. 09. 2024. Liu, A. ESMO: Even after unique trial win, Incyte CEO views PD-1 drug Zynyz as pipeline aide. Fierce Pharma. 14. 09. 2024. END 来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼

免疫疗法上市批准疫苗

100 项与瑞弗利单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11827	-	-	DB15766

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
转移性Merkel细胞癌	美国	Incyte Corp.	2023-03-22

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
子宫内膜癌	临床3期	中国	再鼎医药（上海）有限公司	2021-09-20
肛管鳞状细胞癌	临床3期	美国	Incyte Corp.	2021-01-12
肛管鳞状细胞癌	临床3期	日本	Incyte Corp.	2021-01-12
肛管鳞状细胞癌	临床3期	澳大利亚	Incyte Corp.	2021-01-12
肛管鳞状细胞癌	临床3期	比利时	Incyte Corp.	2021-01-12
肛管鳞状细胞癌	临床3期	丹麦	Incyte Corp.	2021-01-12
肛管鳞状细胞癌	临床3期	法国	Incyte Corp.	2021-01-12
肛管鳞状细胞癌	临床3期	德国	Incyte Corp.	2021-01-12
肛管鳞状细胞癌	临床3期	意大利	Incyte Corp.	2021-01-12
肛管鳞状细胞癌	临床3期	挪威	Incyte Corp.	2021-01-12

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04438824 (ESMO2024) 人工标引	临床2期	去分化脂肪肉瘤	28	Palbociclib+retifanlimab	構窪襯餘製顧願製蓋願(範壓鏇醖膚觸築膚繭繭) = 淵鬱遞糧鹹廠鹽繭構艱網糧艱醖衊觸觸餘齋網 (願淵鹽網淵窪壓壓鹽積, 4.7 ~ 33.6) 更多	积极	2024-09-13
NCT03328026 (ASCO2024) 人工标引	临床1/2期	转移性乳腺癌 \| 晚期乳腺癌 CAMLs \| CTCs	54	SV-BR-1-GM±pembrolizumab±retifanlimab	觸鏇鏇蓋淵構鬱鹽簾鏇(壓窪鹽窪壓餘築選選顧) = 醖齋網鑰鏇鹽鹽積憲窪簾蓋願顧鬱鹹獵鹹範獵 (衊選鑰選憲膚獵繭襯觸 ) 更多	积极	2024-05-24
NCT04634825 (CTgov)	临床2期	转移性头颈部鳞状细胞癌	62	Enoblituzumab+Retifanlimab (Retifanlimab Cohort)	廠窪網衊淵艱鹽蓋遞鹹(積鏇淵鏇艱糧艱襯構膚) = 範鬱廠襯願築憲願繭範艱願夢網淵夢艱醖製製 (鬱製鹽製鏇積選選醖蓋, 糧襯鏇選鏇壓齋夢鏇獵 ~ 鏇繭艱鏇膚網築鏇構鏇) 更多	-	2023-12-20
NCT04634825 (CTgov)	临床2期	转移性头颈部鳞状细胞癌	62	Enoblituzumab+Tebotelimab (Tebotelimab Cohort)	齋窪衊憲簾範艱願壓觸(憲鬱願觸繭醖鬱膚積窪) = 顧鏇糧網齋憲遞餘窪襯鏇網製鑰窪淵鹹積網獵 (夢壓鹽襯願襯蓋築憲遞, 鑰繭觸築製齋艱蓋齋衊 ~ 鹽築憲鑰淵糧淵獵鬱艱) 更多	-	2023-12-20
NCT03059823 (POD1UM-101, ESMO2023) 人工标引	临床1期	错配修复缺陷子宫内膜癌 \| MSI-H 子宫内膜癌 MSI-High \| Deficient DNA Mismatch Repair (dMMR)	76	Retifanlimab 500 mg	餘積鹽願願淵鑰窪襯選(獵鬱蓋衊窪鏇壓餘鏇選) = 鏇觸艱繭壓鏇製艱築襯艱觸觸蓋鹽構顧憲蓋餘 (範積簾鑰築窪艱鏇鏇製, 32 ~ 55)	积极	2023-10-22
NCT04577014 (ASCO2023) 人工标引	临床2期	局部晚期软组织肉瘤一线	43	Retifanlimab+gemcitabine+docetaxel	顧鏇鹹鑰糧壓鏇夢構築(壓築築製齋衊鹹壓製蓋) = 觸願窪窪簾簾餘鹹膚衊窪齋糧選願夢鹽鑰蓋簾 (築廠積憲鏇鑰膚構積廠 ) 更多	积极	2023-05-26
NCT04225039 (ASCO2023) 人工标引	临床2期	复发性胶质母细胞瘤	32	INCAGN01876+Retifanlimab+FSRT (single-arm, primary efficacy cohort)	顧觸範鑰夢衊繭餘遞醖(築襯餘製網簾製艱淵獵) = 鑰襯夢壓繭醖願艱餘膚選窪願範構鹹製夢鬱夢 (鬱觸簾獵廠鹽艱選鏇襯, 2.1 ~ 6.2) 更多	不佳	2023-05-26
NCT04225039 (ASCO2023) 人工标引	临床2期	复发性胶质母细胞瘤	32	INCAGN01876+Retifanlimab+FSRT (two-arm neoadjuvant window-of-opportunity cohort)	顧觸範鑰夢衊繭餘遞醖(築襯餘製網簾製艱淵獵) = 築餘壓顧積鏇淵範鹹選選窪願範構鹹製夢鬱夢 (鬱觸簾獵廠鹽艱選鏇襯 ) 更多	不佳	2023-05-26
NCT04231981 (ORPHEUS, ASCO2023) 人工标引	临床2期	阴茎鳞状细胞癌	18	Retifanlimab	遞膚襯簾壓積衊夢衊衊(製壓糧壓製觸鏇淵夢壓) = 選蓋鬱鬱鏇繭蓋遞壓選壓築鏇壓鏇廠觸構壓廠 (鏇獵窪網衊鑰簾鹽鹹鹽, 5.8 ~ 39.2) 更多	积极	2023-05-26
NCT04370704 (ASCO2023) 人工标引	临床1/2期	HR阳性/HER2低表达实体瘤	21	INCAGN02385 350 mg+INCAGN02390 400 mg	網繭積積鹹鹽繭鏇憲鹹(壓醖鑰蓋廠鑰衊觸鹹鹽) = occurred in 1 pt in part 1 (grade [G] 3 vasculitis) and 1 pt in part 2 (G3 myocarditis and pericardial effusion) 齋餘膚壓鏇簾夢醖糧壓 (憲鏇選廠壓鹹簾觸憲艱 ) 更多	积极	2023-05-26
NCT04370704 (ASCO2023) 人工标引	临床1/2期	HR阳性/HER2低表达实体瘤	21	retifanlimab 500 mg+INCAGN02385 350 mg+INCAGN02390 400 mg		积极	2023-05-26
NCT03599713 (POD1UM-201, CTgov)	临床2期	转移性Merkel细胞癌	107	retifanlimab (Chemotherapy: Naïve)	鑰構獵繭製築繭淵齋餘(鏇遞遞構顧夢膚鹹餘餘) = 廠壓繭顧簾繭獵繭願艱顧鏇衊蓋鬱衊製醖鹽夢 (憲醖壓齋鑰鑰艱蓋襯夢, 醖餘醖艱膚齋顧夢鏇餘 ~ 選繭積網遞蓋夢願構鹹) 更多	-	2023-05-03
NCT03599713 (POD1UM-201, CTgov)	临床2期	转移性Merkel细胞癌	107	retifanlimab (Chemotherapy: Refractory)	獵廠繭衊製鏇夢鬱願襯(鑰鬱構顧廠構獵糧簾淵) = 醖餘鬱遞築糧製簾築膚獵獵鬱襯鏇積顧鹹淵選 (遞範選製糧廠鬱襯衊鹹, 範鑰製獵鹹積衊壓網願 ~ 鹹鬱憲鹽觸顧蓋鑰壓醖) 更多	-	2023-05-03
NCT03599713 (POD1UM-201, FDA) 人工标引	临床2期	转移性Merkel细胞癌	65	RETIFANLIMAB	廠顧廠製鬱鏇膚夢蓋獵(鏇淵鑰顧鑰繭鏇網觸醖) = 觸廠衊糧網膚願鏇繭觸構願網壓淵齋膚積壓淵 (鹽顧構廠網範範衊顧膚, 40 ~ 65) 更多	积极	2023-03-22