Paclitaxel

AGOURA HILLS, Calif., Dec. 03, 2025 (GLOBE NEWSWIRE) -- Oncotelic Therapeutics, Inc. (OTCQB: OTLC) 45% owned Joint Venture, Sapu Nano today announced new pharmacokinetic (PK) and tissue-distribution results demonstrating that Sapu003, the company’s intravenous (IV) Deciparticle™ formulation of everolimus, substantially reduces gastrointestinal (GI) drug accumulation, addressing one of the most significant and well-recognized limitations of oral everolimus (Afinitor®). The data indicate that Sapu003 may offer improved tolerability while preserving the drug’s intrinsic metabolic profile and enabling more consistent systemic exposure. IV Sapu003 Reduces GI Exposure to Everolimus by 67-Fold Compared With Oral Dosing New tissue-distribution data show that Sapu003, delivered intravenously, eliminates the extreme gastrointestinal accumulation characteristic of oral everolimus. After oral dosing, everolimus reaches 2,448× plasma levels in the stomach, 750× plasma in the small intestine, and 323× plasma in the large intestine, confirming that the gut is the dominant exposure site for the oral formulation. In contrast, IV Sapu003 demonstrates only 36–48× plasma levels across the same GI tissues, representing a 67-fold reduction in stomach exposure, a 15.7-fold reduction in small-intestinal exposure, and a 7.4-fold reduction in large-intestinal exposure. These findings provide a clear mechanistic explanation for the well-documented GI toxicity of oral everolimus—including stomatitis, mucositis, abdominal discomfort, and diarrhea. Presentation information: PS4-06-05. Sapu003: Everolimus for Injection — Pharmacokinetic Rationale for Phase I Evaluation in HR⁺/HER2⁻ Metastatic Breast Cancer. Wen-Han Chang, John Lopp, Sheng-Hao Min, Robert Hoff, Nancy Chang, Tanjina Hoque, Ann Park, and Cynthia Lee. Potential for Improved Clinical Tolerability and Antitumor Potency By bypassing the gastrointestinal tract and delivering the drug directly into circulation, Sapu003: Avoids the high local GI concentrations associated with oral toxicityProduces more consistent systemic exposureEnhances drug penetration into tumor-relevant tissues These PK advantages complement previously reported efficacy findings in which Sapu003 achieved 97–98% tumor inhibition in glycolysis-addicted xenograft while outperforming paclitaxel. Management Commentary “The fundamental challenge with oral everolimus is that the majority of the drug ends up in the gut, leading directly to the GI toxicity that limits its use,” said Dr. Cynthia Lee, VP of R&D. “These new data show that IV Sapu003 avoids that problem entirely. By reducing GI accumulation by up to 67-fold, Sapu003 has the potential to offer a far more tolerable and clinically versatile version of everolimus.” About Sapu003 Sapu003 is a novel intravenous nanoparticle formulation of everolimus engineered using Sapu Nano’s proprietary Deciparticle™ technology. It is designed to overcome the poor bioavailability, intestinal toxicity, and variable patient exposure seen with oral everolimus while enabling reliable, predictable weekly IV dosing. About the Deciparticle™ Platform The Deciparticle™ platform is a proprietary nanotechnology engineered to encapsulate hydrophobic molecules as uniform, sub-20 nm nanoparticles for intravenous administration. The platform improves systemic exposure, reduces GI deposition, and supports precision delivery while maintaining manufacturability at clinical scale. About Sapu Nano Sapu Nano is a clinical-stage biotechnology company developing Deciparticle™ nanomedicine therapeutics designed to optimize the delivery of hydrophobic oncology agents and peptide-based therapeutics. The company operates an integrated ISO-5 cGMP manufacturing facility supporting rapid progression from formulation to clinical trial supply. For more information, visit www.sapunano.com. About Oncotelic Oncotelic (f/k/a Mateon Therapeutics, Inc.), was formed in the State of New York in 1988 as OXiGENE, Inc., was reincorporated in the State of Delaware in 1992, and changed its name to Mateon Therapeutics, Inc. in 2016, and Oncotelic Therapeutics, Inc. in November 2020. Oncotelic is seeking to leverage its deep expertise in oncology drug development to improve treatment outcomes and survival of cancer patients with a special emphasis on rare pediatric cancers. Oncotelic has rare pediatric designation for Diffuse Intrinsic Pontine Glioma “DIPG” (through OT-101) through its 45% joint venture, melanoma (through CA4P), and Acute Myeloid Leukemia “AML” (through OXi 4503). Oncotelic also acquired PointR Data Inc. in November 2019. Oncotelic acquired AL-101, during the 4th quarter of 2021, for the intranasal delivery of apomorphine. We intend to develop AL-101 for the treatment of Parkinson Disease ("PD"). Over 60,000 new patients are being diagnosed with PD in the United States and currently there are over 1 million patients in the US and expected to increase to over 1.2 million by 2030. In addition, approximately 10 million suffer from this disease globally. https://www.parkinson.org/Understanding-Parkinsons/Statistics. AL-101 is also being developed for Erectile Dysfunction ("ED"). ED is the most prevalent male sexual disorder globally. The percentages of men affected by ED are as follows: 14.3-70% of men aged 60 years, 6.7-48% of men aged 70 years, and 38% of men aged 80 years (Geerkens MJM et al. (2019). Eur Urol Focus. pii: S2405-4569(19)30079-3). However, with the increasing administration of PDE5 inhibitors in clinical practice, it was found that approximately 30-35% of ED patients are treatment failures (McMahon CN et al. (2006). BMJ, 332: 589-92). AL-101 is designed to target treatment failure ED patients who do not respond to PDE5 inhibitors. Through similar mechanism of action, AL-101 is being developed for Female Sexual Dysfunction ("FSD"). Female sexual dysfunction is a prevalent problem, afflicting approximately 40% of women and there are few treatment options. FSD is more typical as women age and is a progressive and widespread condition. (Allahdadi, KJ et al. (2009) Cardiovascular & hematological agents in medicinal chemistry, 7(4), 260-269). There is no available drug for the treatment of FSD. In June 2019, the U.S. Food and Drug Administration approved Vyleesi (bremelanotide) to treat acquired, generalized hypoactive sexual desire disorder ("HSDD") in premenopausal women. This is the only available drug treatment. Vyleesi has essentially replaced the only other drug for HSDD - however, it has a long list of drug-drug interactions, including commonly used antidepressants, such as fluoxetine and sertraline. In addition, it has a black box warning regarding its use with alcohol, a combination that has been associated with hypotension and syncopal episodes. Therefore, there is an urgent need for effective therapy against FSD and HSDD. Oncotelic's Cautionary Note on Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act and Section 21E of the Securities Exchange Act of 1934 (the “Exchange Act”) that involve substantial risks and uncertainties. We generally identify forward-looking statements by terminology such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “would,” “intend,” “target,” “aim,” “project,” “believe,” “estimate,” “predict,” “potential,” “seek,” “indicate,” or “continue” or the negative of these terms or other similar words, although not all forward-looking statements contain these words. Forward-looking statements include, but are not limited to, statements regarding our or our management’s expectations, hopes, beliefs, intentions or strategies regarding the future, such as our estimates regarding anticipated operating income or losses, future performance, future revenues and projected expense, including that to fund our clinical and other development programs; our liquidity and our expectations regarding our needs for and ability to raise additional capital; our ability to continue as a going concern; our ability to select and capitalize on commercially desirable product opportunities as a result of limited financial resources; our ability to manage our expenses effectively and raise the funds needed to continue our business; our ability to retain the services of our current or future executive officers, directors and principal consultants; the competitive nature of our industry and the possibility that our products or product candidates may become obsolete or may not generate revenues as expected or at all; our ability to obtain and maintain regulatory approval of our existing products and any future products we may develop; the development of and the process of commercializing AI/Blockchain and other technologies for supporting the development of OT- 101 and Artemisinin for COVID-19, OT-101, including development of OT-101, Artemisinin, OXi4503, CA4P and our 2021 in-licensing of apomorphine; the initiation, timing, progress and results of our preclinical and clinical trials, research and development programs; regulatory and legislative developments in the United States and foreign countries; the timing, costs and other limitations involved in obtaining regulatory approval for any product; the further preclinical or clinical development and commercialization of our product candidates; the entering into any corporate transactions to develop our products through partnerships, joint ventures or other corporate transactions; our ability to make a proposed initial public offering between us and our joint-venture partners for the joint venture, statements about future plans related to the operations of the JV, taking the JV into an initial public offering or the success thereof: building and the success of our nanoparticle platform and the related success of launching the platform; the expected valuation of the JV, and therefore a corresponding increase in the valuation of the Company, by virtue of it’s ownership in the JV; the success of the launch of Pet2DAO, a corporation with a DAO infrastructure, the success of Pet2DAO and the plans surrounding the pet and animal health, the ability for the Company to register the tokens of Pet2DAO, the actual filing of a registration statement and approval of the tokens as registrable securities with the Securities and Exchange Commission (“SEC”) through a registration statement, the ability of the tokens to be tradable or any value such tokens may have if they become tradable; our ability to obtain and maintain orphan drug exclusivity for some of our product candidates; the potential benefits of our product candidates over other therapies; our ability to enter into and maintain any collaboration with respect to product candidates; our ability to continue to develop or commercialize our products or product candidates in the event any license agreements in place with third parties expire or are terminated; the performance and conduct of third parties, including our third-party manufacturers and third party service providers used in our clinical trials; our ability to obtain and maintain intellectual property protection for our products and operate our business without infringing upon the intellectual property rights of others; the potential liability exposure related to our products and our insurance coverage for such exposure; our ability to form alliances with other third parties to develop the products in our pipeline through partnerships, joint ventures, mergers or acquisitions; the successful development of our sales and marketing capabilities; the size and growth of the potential markets for our products and our ability to serve those markets; the rate and degree of market acceptance of any future products; the volatility of the price of our common stock; the ability to achieve secondary trading of our stock in certain states; the dilutive effects of potential future equity issuances; our expectation that no dividends will be declared on our common stock in the foreseeable future; our ability to maintain an effective system of internal controls; the payment and reimbursement methods used by private or governmental third-party payers; our ability to retain adequate staffing levels; unfavorable global economic conditions; unfavorable global epidemic and pandemic conditions; a failure of our internal computer systems or those of our contractors and consultants; potential misconduct or other improper activities by our employees, contractors or consultants; the ability of our business continuity and disaster recovery plans to protect us in the event of a natural disaster; and other factors discussed elsewhere in this document or any document incorporated by reference herein or therein. Contact Information:For Oncotelic Therapeutics, Inc.:Investor Relationsir@oncotelic.com

替雷利珠单抗注射液（百泽安®）【药品说明书】 【通用名称】替雷利珠单抗注射液 【商品名称】百泽安® 【英文名称】Tislelizumab Injection 【汉语拼音】Tileilizhu Dankang Zhusheye 【成份】活性成份：替雷利珠单抗，针对程序性死亡受体-1（PD-1）的人源化单克隆抗体（IgG4 变体）。 辅料：柠檬酸钠二水合物、柠檬酸一水合物、L-组氨酸盐酸盐一水合物、L-组氨酸、海藻糖二水合物、聚山梨酯 20 和注射用水。 【性状】本品为澄清至可带轻微乳光，无色至淡黄色液体。 【适应症】本品适用于至少经过二线系统化疗的复发或难治性经典型霍奇金淋巴瘤的治疗。 本品适用于 PD-L1 高表达的含铂化疗失败包括新辅助或辅助化疗 12 个月内进展的局部晚期或转移性尿路上皮癌的治疗。 上述适应症是分别基于一项单臂临床试验的客观缓解率和缓解持续时间结果给予的有条件批准。上述适应症的完全批准将取决于正在计划开展中的确证性随机对照临床试验能否证实本品治疗相对于标准治疗的显著临床获益。 本品联合紫杉醇和卡铂用于局部晚期或转移性鳞状非小细胞肺癌的一线治疗。 【规格】10ml:100mg 【用法用量】本品须在有肿瘤治疗经验的医生指导下用药。 在局部晚期或转移性尿路上皮癌中使用本品应选择 PD-L1 高表达的患者。PDL1 表达由国家药品监督管理局批准的检测方法进行评估。 PD-L1 表达是通过免疫组化法进行测定，PD-L1 高表达定义为： • 如果肿瘤浸润免疫细胞数>1%，则定义为≥25%的肿瘤细胞或≥25%的免疫细胞存在 PD-L1 表达 ； • 如果肿瘤浸润免疫细胞数≤1%，则定义为≥25%的肿瘤细胞或所有免疫细胞（100%）存在 PD-L1 表达。 推荐剂量 本品采用静脉输注的方式给药，推荐剂量为 200 mg，每 3周给药一次。用药直至疾病进展或出现不可耐受的毒性。 本品与化疗联用时，若为同日给药则先输注本品。 有可能观察到非典型疗效反应（例如最初几个月内肿瘤暂时增大或出现新的病灶，随后肿瘤缩小或新病灶消失）。如果患者临床症状稳定或持续减轻，即使有初步的疾病进展表现，基于总体临床获益的判断，可考虑继续应用本品治疗，直至证实疾病进展。 根据个体患者的安全性和耐受性，可能需要暂停给药或永久停药，不建议增加或减少剂量。有关暂停给药和永久停药的指南，请参见表 1。有关免疫相关性不良反应管理的详细指南，请参见【注意事项】。 表 1：本品推荐的治疗调整方案 注：按照美国国立癌症研究所的不良事件通用术语评估标准 4.03 版（NCI-CTCAE v4.03）确定严重程度分级。 *心肌炎经治疗改善到 0~1 级后重新开始本品治疗的安全性尚不明确。 特殊人群 肝功能不全 目前本品尚无充分针对中重度肝功能不全患者的研究数据，中度或重度肝功能不全患者不推荐使用。轻度肝功能不全患者应在医生指导下慎用本品，如需使用，无需进行剂量调整。 肾功能不全 目前本品尚无针对重度肾功能不全患者的研究数据，重度肾功能不全患者不推荐使用。轻度或中度肾功能不全患者应在医生指导下慎用本品，如需使用，无需进行剂量调整。 儿童人群 尚无本品在 18 岁以下儿童及青少年中的安全性和有效性数据。 老年人群 本品目前在≥65 岁的老年患者中应用数据有限，建议在医生的指导下慎用，如需使用，无需进行剂量调整。 给药方法 本品仅供静脉输注使用。第一次输注时间应不短于 60 分钟；如果耐受良好，则后续每一次输注时间应不短于 30 分钟。输注时所采用的输液管须配有一个无菌、无热源、低蛋白结合的输液管过滤器（孔径 0.2 或 0.22 μm）。 本品不得采用静脉推注或单次快速静脉注射给药。将本品用注射用氯化钠溶液（9 mg/ml，0.9%）稀释至 1~5 mg/ml 之间的浓度后进行静脉输注。 给药前药品的稀释指导如下： 溶液制备和输液 ●请勿摇晃药瓶。 ●药品从冰箱中取出后，稀释前可在室温下（25°C 及以下），最长放置 2 小时。 ●应目视检查注射用药是否存在悬浮颗粒和变色的情况。本品是一种澄清至微乳光、无色至淡黄色液体。如观察到可见颗粒或异常颜色，应弃用药物。 ●抽取两瓶本品注射液（共 20 ml，含本品 200 mg），转移到含有注射用氯化钠溶液（9 mg/ml，0.9%）的静脉输液袋中，制备终浓度范围为 1~5mg/ml。将稀释液缓慢翻转混匀。 ●本品不含任何防腐剂。建议从冰箱取出后立即进行溶液制备，稀释后溶液建议立即使用。如不能立即使用，稀释液可保存不超过 24 小时，该 24 小时包括冷藏条件下（2~8°C）储存不超过 20 小时，以及恢复至室温（25°C及以下）且完成输液不超过 4 小时。 ●本品不得冷冻。 ●请勿使用同一输液管与其他药物同时给药。 ●本品仅供一次性使用。必须丢弃药瓶中剩余的任何未使用的药物。 【不良反应】本说明书描述了在临床试验中观察到的可能由本品引起的不良反应近似发生率。由于临床试验在各种不同条件下进行，因此在不同临床试验中观察到的不良反应的发生率不能直接比较，也可能不能反映临床实践中的实际发生率。 安全性特性总结 单药治疗 本产品的安全性信息来自四项单药临床研究（BGB-A317-001 [N=451]，BGBA317-102 [N=300]，BGB-A317-203 [N=70]和 BGB-A317-204 [N=113]），共涉及934 例患者。肿瘤类型包括尿路上皮癌（N=152）、非小细胞肺癌（N=105）、食道癌（N=81）、胃癌（N=78）、经典型霍奇金淋巴瘤（N=70）、肝细胞癌（N=69）、结直肠癌（N=54）、卵巢癌（N=51）、肾细胞癌（N=37）、黑色素瘤（N=36）、乳腺癌（N=32）、头颈部鳞状细胞癌（N=29）、鼻咽癌（N=27）、胆管癌（N=18）、胰腺癌（N=10）、小 细 胞 神经内分泌癌（N=10）、肉 瘤（N=10）、间皮瘤（N=9）、宫颈癌（N=7）、其他类型肿瘤（N=49）。上述研究中496例接受了200 mg 每 3 周 1 次的本品治疗，355例接受了 5 mg/kg 每 3 周 1 次的本品治疗，各有 26 例分别接受了 2 mg/kg 或 5 mg/kg 每 2 周 1 次的本品治疗，21例接受了 2 mg/kg 每 3 周 1 次的本品治疗，7 例接受了 10 mg/kg 每 2 周 1 次的本品治疗，3例接受了 0.5 mg/kg每 2周 1次的本品治疗。本品中位给药时间为 16周（范围：0.6~160.4 周），36.1%的患者接受本品治疗≥ 6 个月，20.6%的患者接受本品治疗≥12 个月。 接受本品治疗的 934 例患者中所有级别的不良反应发生率为 70.8%，发生率≥10%的不良反应包括：皮疹、疲乏、丙氨酸氨基转移酶升高。 3 级及以上不良反应发生率为 21.8%，发生率≥1%的包括： γ-谷氨酰转移酶升高、贫血、天门冬氨酸氨基转移酶升高、丙氨酸氨基转移酶升高、肺炎（非感染性）、重度皮肤反应、低钾血症。 与化疗联合治疗 本产品与化疗联合治疗在鳞状非小细胞肺癌患者中的安全性信息来自两项临床研究BGB-A317-307[N=238]和BGB-A317-206解癌队列[N=21],共涉及259例患者。患者均接受了200mg每3周1次的本品治疗。本品中位给药时间为32.1周(范围：2.9~71.7周);66.0%的息者接受本品治疗≥6个月，10.8%的患者接受本品治疗≥12个月。 接受本品联合治疗的259例患者所有级别的不良反应发生率为85.7%,发生率>20%的不良反应包括(研究者判定为与本品相关的不良反应发生率):贫血(34.0%)、中性粒细胞减少症(32.0%)、白细胞减少症(31.3%)、血小板减少症(30.1%)和皮疹(21.2%)。 发生率≥2%的3级及以上不良反应包括(研究者判定为与本品相关的不良反应发生率):中性粒细胞减少症(20.1%)、白细胞减少症(13.1%)、贫血(7.3%)、血小板减少症(6.6%)、皮疹(3.1%)和肺部炎症(非感染性)(2.3%)。 不良反应汇总表 表2列出了本品在临床研究中单药泊疗(934例患者)或与化疗联合治疗(259例患者)中观察到的不良反应。本品单药治疗已知的不良反应，即使可能尚未在本品联合化疗的临床研究中观察到，仍有可能在本品联合化疗的治疗中出现。以下不良反应按系统器官分类和发生频率列出。频率定义为：十分常见(≥1/10);常见(≥1/100至<1/10);偶见≥1/1000至<1/100);罕见(≥1/10000至1%，则定义为≥25%的肿瘤细胞或≥25%的免疫细胞存在 PD-L1 表达。 ●如果肿瘤浸润免疫细胞数≤1%，则定义为≥25%的肿瘤细胞或所有免疫细胞（100%）存在 PD-L1 表达。 根据临床试验方案定义的有效性可评价人群为基线时由 IRC 根据 RECIST 1.1版评估具有可测量病灶的患者（104 例），且排除了 3 例铂类化疗不耐受的患者。符合该有效性可评价人群的患者共 101 例。患者的中位年龄为 62.0 岁（范围：36~81岁）。其中 75例为男性（74.3%），98 例来自中国（97.0%）。51.5%的患者基线 ECOG 体能状态评分为 1。75.2%的患者发生内脏器官转移，其中 24.8%的患者发生肝转移。24.8%的患者仅发生淋巴结转移。从初次诊断尿路上皮癌至入组研究的中位时间为 17.7 个月（范围：2.9~125.7 月）。原发性肿瘤的最常见部位为膀胱（45 例，44.6%），其次为肾盂（29 例，28.7%）和输尿管（20 例，19.8%）。所有患者均为尿路上皮移行细胞癌，79.2%为高级别尿路上皮癌。所有患者的疾病在基线时均为晚期（IV期）。所有患者均接受过至少 1个含铂类药物的治疗方案。入组前的末次治疗结束时间至入组研究的中位时间为 4.0 个月（范围：0.7~42.8月）。末次治疗的目的 17.8%为针对疾病进行的新辅助或辅助治疗，65.3%为一线治疗，16.8%为二线治疗。 该研究从首次用药起每 9 周（±1 周）进行一次肿瘤状态的影像学评估。由 IRC根据 RECIST 1.1 版，同时由研究者根据 RECIST 1.1 版和 irRECIST 进行肿瘤评估。 主要有效性终点是由 IRC 根据 RECIST 1.1 版评估的基线期有可测量病灶的受试者的总体缓解率（ORR），次要疗效终点包括由 IRC 评估的无进展生存期（PFS），缓解持续时间（DOR），疾病控制率（DCR），以及由研究者评估的总体缓解率（ORR），无进展生存期（PFS），缓解持续时间（DOR）和疾病控制率（DCR）。最后 1 例入组受试者至少随访 12 个月。关键有效性结果总结见表 4。 表 4: BGB-A317-204 研究关键有效性结果（由独立审查委员会根据 RECIST 1.1 版评估） 缩写词：CI=置信区间；NE=未达到。 1 双侧 Clopper-Pearson 95%CI。 † 基于 Kaplan-Meier 估计值。 *排除了 3 例铂类化疗不耐受的病例。 基于研究者评估基线期有可测量病灶的受试者，排除 3 例铂类化疗不耐受的受试者，共 110 例，研究者评价的 ORR 为 24.5%（95% CI: 16.84, 33.67），包括 5 例CR 及 22 例 PR 患者。DCR 为 42.7%（95% CI: 33.34, 52.52），中位缓解持续时间未达到 （95% CI: 10.41, NE）。中位 PFS 为 2.2 个月（95% CI: 2.07, 4.04），6 个月的 PFS 率为 33.6% （95% CI: 24.88, 42.53），12 个月的 PFS 率为 25.0% （95% CI:17.21, 33.46）。中位 OS 为 10.1 个月（95% CI: 7.46, 13.01），6 个月的 OS 率为 66.5%（95% CI: 56.75, 74.59），12 个月的 OS 率为 42.8%（95% CI：33.26, 51.92）。 鳞状非小细胞肺癌 在一项多中心、随机、开放、Ⅲ期临床研究(BGB-A317-307)中评价了替雷利珠单抗联合化疗用于局部晚期或转移性姨状非小细胞肺癌的有效性和安全性。研究入组360例未经治疗的局部晚期或转移性镇状非小细胞肺感愚者，按照1:1:1随机分配并接受替雷利珠单抗200mg联合紫杉醇175mg/m²及卡铂AUC5mg/ml/min(A组，n=120)或替雷利珠单抗200mg联合注射用紫杉醇(白蛋白结合型)100mg/m²及卡铂AUC 5mg/ml/min(B组，n=119)或紫杉醇175mg/m²及卡铂AUC 5mg/ml/min(C组，n=121)。以上治疗静脉输注每3周1次。经过4-6个周期(具体周期数由研究者决定)后，A组和B组继续接受替雷利珠单抗200mg每3周1次治疗直至疾病进展或不可接受的毒性，出现疾病进展但经研究者评价仍可临床获益的患者可继续接受替雷利珠单抗治疗；C组患者疾病进展后可交叉接受替雷利珠单抗200mg每3周1次治疗。 360例患者中，中位年龄62.0岁，64.7%为65岁以下；91.7%为男性；23.6%美国东部肿瘤协作组体能状态评分(ECOG PS)为0分，76.4%为1分，33.9%为ⅢB期，66.1%为IV期；16.4%既往无吸烟史；40%程序性死亡受体-配体1(PD-L1)表达<1%,25.3%PD-L1表达≥1%且≤49%,34.7% PD-L1表达50%;8.1%既往接受抗肿瘤手术，4.4%既往接受抗肿瘤放射治疗，8.1%既往接受抗肿瘤化学治疗。三组基线年龄、性别、FCOG评分、分期.既往吸烟史、PD-L1表达、既往抗肿瘤治疗史具有可比性。 主要研究终点为由独立审查委员会(IRC)评估的无进展生存期(PFS),次要终点包括由TRC评估的客观级解率(ORR)、由IRC评估的持续缓解时间(DoR)等。替雷利珠单抗联合紫杉醇及卡铂的关键性有效性结果总结见表5,Kaplap-Mcier生存曲线见图1.由于注射用紫杉醇(白蛋白结合型)相同适应症尚未获批，因此表5及图1仅提供BGB-A312-307研究中替雷利珠单抗联合紫杉醇及卡铂(A组),紫杉醇及卡铂(C组)数据。 【药理毒理】药理作用 本品为人源化重组抗PD-1 单克隆抗体。T 细胞表达的 PD-1 受体与其配体 PD-L1 和 PD-L2 结合，可以抑制 T 细胞增殖和细胞因子生成。部分肿瘤细胞的 PD-1 配体上调，通过这个通路信号传导可抑制激活的 T 细胞对肿瘤细胞的免疫监视。本品与人重组 PD-1 结合的 EC50为 0.12 nM，Kd 值为 1.45×10-10（PD-1 低密度）、1.10×10-11（PD-1 高密度），抑制 PD-1 与 PD-L1 结合的 IC50 约为 0.5 nM，抑制 PD-1与 PD-L2 结合的 IC50约为 0.4~0.6 nM。 毒理研究 遗传毒性：本品尚未进行遗传毒性试验。 生殖毒性：本品未进行生殖毒性试验。 本品在食蟹猴重复给药毒性试验中，雌、雄动物生殖器官均未见肉眼可见的病变或组织病理学改变。 通过保持母体对胎仔的免疫耐受来维持妊娠是 PD-1/PD-L1 通路的主要功能之一。阻断妊娠啮齿类动物模型的PD-L1信号通路可破坏母体对胎仔的耐受性，导致胎仔丢失增加。妊娠期间给予本品有潜在的风险，包括流产或死胎的比例增加。基于本品的作用机制，胎仔暴露于本品可增加发生免疫介导紊乱或改变正常免疫应答的风险。 致癌性：本品尚未进行致癌性试验。 其它毒性：文献资料显示，在动物模型中抑制 PD-1 信号可加重感染和炎症反应。结核分枝杆菌感染的 PD-1 基因敲除小鼠较野生型小鼠存活率明显下降，同时细菌增殖和炎症反应增加。PD-1 基因敲除小鼠感染淋巴细胞性脉络丛脑膜炎病毒后存活率下降。 【药代动力学】本品的药代动力学数据来自于三项临床研究（BGB-A317-001，BGB-A317-102和 BGB-A317-203）的 798 例晚期恶性肿瘤患者的群体药代动力学分析，及 112 例晚期恶性肿瘤患者的非房室模型药代动力学分析。上述患者每两周接受 0.5、2、5或 10 mg/kg，或每三周接受 2 或 5 mg/kg，或每三周接受 200 mg 本品。单次静脉输注本品后，在 0.5 mg/kg 至 10 mg/kg 剂量范围内，药物暴露量（Cmax和 AUC0-14d）随剂量成比例增加。 吸收 本品采用静脉输注方式给药，因此生物利用迅速且完全。 分布 中国晚期实体瘤患者（n=19）单次静脉输注本品 200 mg 后，本品的平均分布容积（±SD）为 4.41±1.04 L。 基于群体药代动力学分析，本品稳态分布容积（Vss）为 5.247 L。 消除 中国晚期实体瘤患者（n=20）单次静脉输注本品 200 mg 后，本品的平均清除率（±SD）为 0.247±0.0918 L/天，平均半衰期（±SD）为 13.3±2.95 天。 基于群体药代动力学分析，本品清除率为 0.171 L/天，个体间变异为 31.9%，终末半衰期约为 26 天。 特殊人群药代动力学 儿童与青少年：本品尚无儿童及青少年人群的临床试验数据。 肾损害：本品尚未开展直接评价肾功能损害对药代动力学影响的临床试验。 基于群体药代动力学分析，轻度或中度肾损害未对本品药代动力学产生显著影响。本品在重度肾损害患者中尚无足够数据。 肝损害：本品尚未开展直接评价肝功能损害对药代动力学影响的临床试验。 基于群体药代动力学分析，轻度肝损害未对本品药代动力学产生显著影响。本品在中度和重度肝损害患者中尚无足够数据。 【贮藏】于 2~8℃避光保存和运输，请勿冷冻。 【包装】1 瓶/盒。 【有效期】24个月。 【药品上市许可持有人】企业名称：百济神州（上海）生物科技有限公司 企业地址：中国（上海）自由贸易试验区蔡伦路 780 号 4 楼 D 座 邮政编码：201203 【受托生产企业】企业名称：勃林格殷格翰生物药业（中国）有限公司 生产地址：中国（上海）自由贸易试验区哈雷路 1090 号 包装地址：中国（上海）自由贸易试验区李时珍路 257 号 邮政编码：201203 【医学咨询电话】电话：400 820 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