PD-L1 positive Triple Negative Breast Cancer

▎药明康德内容团队报道今日（3月16日），中国国家药监局药品审评中心（CDE）官网公示，由第一三共（Daiichi Sankyo）申报的注射用datopotamab deruxtecan（Dato-DXd）上市申请获得受理。公开资料显示，这是一款Trop2靶向抗体偶联药物（ADC），由阿斯利康（AstraZeneca）和第一三共共同开发并在全球范围内商业化。据悉，该产品本次申报上市的适应症为乳腺癌。截图来源：CDE官网Dato-DXd（即DS-1062a）采用第一三共独有的DXd-ADC技术设计，由人源化抗TROP2 IgG1单克隆抗体通过可裂解四肽连接子与多个拓扑异构酶I抑制剂有效载荷（一种依喜替康衍生物，DXd）连接组成。针对该产品，研究人员正在全球范围内开展临床研究，评估其在多种癌症中的疗效和安全性，包括NSCLC、三阴乳腺癌（TNBC）和HR阳性、HR2低表达或阴性乳腺癌。2024年2月，Dato-DXd的生物制品许可申请（BLA）已获美国FDA接受，用于治疗既往接受过全身治疗的局部晚期或转移性非鳞状非小细胞肺癌（NSCLC）成年患者，PDUFA日期为2024年第四季度。根据第一三共早先新闻稿介绍，如果获得批准，该疗法将会是首个Trop2靶向ADC疗法获批用于治疗肺癌患者。此外，Dato-DXd已经在关键性3期临床研究TROPION-Breast01中显示积极结果。基于该研究，Dato-DXd的一项BLA申请正在等待美国受理，针对的适应症为用于治疗转移性激素受体（HR）阳性、HER2阴性（IHC 0、IHC 1+或IHC 2+/ISH-）乳腺癌成人患者。图片来源：123RFTROPION-Breast01的研究结果显示，在双主要终点分析中，经盲态独立中心影像（BICR）评估，与研究者所选化疗相比，Dato-DXd可将HR阳性、HER2低表达或阴性转移性乳腺癌患者的疾病进展或死亡风险降低37%。Dato-DXd治疗组的中位PFS为6.9个月（vs.化疗组4.9个月）。在不同的亚组中均观察到一致的PFS获益。此外，分析结果还显示Dato-DXd治疗组的客观缓解率（ORR）为36.4%（vs 化疗组为22.9%）。 根据中国药物临床试验登记与信息公示平台官网，研究人员正在针对Dato-DXd开展多项国际多中心（含中国）3期临床研究，包括：在PD-L1阳性的局部复发、不可手术或转移性三阴乳腺癌患者中比较Dato-DXd联合或不联合度伐利尤单抗与研究者所选化疗联合帕博利珠单抗的3期研究；在不适用PD-1/PD-L1抑制剂治疗的局部复发无法手术或转移性三阴性乳腺癌患者中比较Dato-DXd与研究者所选化疗的3期研究；在新辅助治疗后的三阴性乳腺癌患者中比较Dato-DXd联合或不联合度伐利尤单抗与研究者所选治疗的研究；比较Dato-DXd和度伐利尤单抗以及卡铂联合治疗与帕博利珠单抗和含铂化疗联合治疗，作为无驱动基因改变的局部晚期或转移性NSCLC患者一线治疗的随机、开放性、多中心、全球3期研究（AVANZAR）；在既往经治的晚期或转移性非小细胞肺癌患者中比较DS-1062a和多西他赛的3期研究；在接受化疗后出现疾病进展的无法手术或转移性激素受体阳性、HER2阴性乳腺癌患者中比较Dato-DXd与研究者所选化疗的3期研究。希望Dato-DXd在后续研究中也进展顺利，早日造福更多的患者。参考资料：[1]中国国家药监局药品审评中心（CDE）官网. Retrieved Mar 16, 2024 from https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d[2]FDA正式受理Dato-DXd生物制品上市许可申请，用于治疗既往接受过治疗的晚期非鳞状非小细胞肺癌患者 . Retrieved Feb 20, 2024 from https://mp.weixin.qq.com/s/KpqDp20xL_xlnJtWHlPMuA[3]III期研究TROPION-Breast01显示，Dato-DXd相较于化疗显著延长HR阳性mBC患者的无进展生存期 . Retrieved Oct 25, 2023 from https://mp.weixin.qq.com/s/RnOULg6xXG7EuRVd86Yn0w本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转发授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

Subcutaneous (SC) injection offers the potential for a faster, more convenient alternative to intravenous (IV) infusion and is preferred by cancer patients, nurses and physicians1-5 Tecentriq SC reduces treatment time by approximately 80%, compared with standard IV infusion6 Roche is working closely with national health systems in Europe to ensure patients can access Tecentriq SC as quickly as possible 16 January 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the European Commission has granted marketing authorisation for Tecentriq® SC (atezolizumab), the European Union (EU)’s first PD-(L)1 cancer immunotherapy for subcutaneous (under the skin) injection. Last year, more than 38,000 people in the EU received Tecentriq to treat different types of lung, liver, bladder and breast cancer.7 Until now, Tecentriq has been given directly into patients’ veins by IV infusion which takes approximately 30-60 minutes.6 The new subcutaneous injection will cut treatment time to approximately seven minutes, with most injections taking between four and eight minutes.6 The marketing authorisation applies to all approved indications of Tecentriq IV.7 “We are pleased to introduce the first subcutaneous PD-L1 cancer immunotherapy in Europe,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “Giving Tecentriq subcutaneously provides more flexibility to patients, while also helping to free up resources in constrained healthcare systems.” “Ensuring the best possible quality of life is crucial for people living with cancer,” said Dr. Enriqueta Felip, Head of the Thoracic Cancer Unit of Vall d'Hebron Hospital, Spain. “The availability of a subcutaneous cancer immunotherapy option that can minimise the time receiving treatment and even allow for treatment outside of a hospital will undoubtedly make a significant difference to patients and their loved ones.” The approval is based on pivotal data from the Phase IB/III IMscin001 study, which showed comparable levels of Tecentriq in the blood, when administered subcutaneously, and a safety and efficacy profile consistent with the IV formulation.6,8 90% of healthcare professionals who were surveyed as part of the study agreed that the SC formulation is easy to administer and 75% said it could save time for healthcare teams compared with the IV formulation.6 In addition to offering shorter treatment time, Tecentriq SC may be administered by a healthcare professional outside of the hospital, in a community care setting or at a patient's home, depending on national regulations and health systems. Roche is in discussion with several providers in Europe to include Tecentriq SC in cancer homecare initiatives where possible. IMscin001 is a Phase IB/III, global, multicentre, randomised study evaluating the pharmacokinetics, safety and efficacy of Tecentriq SC, compared with Tecentriq IV, in patients with previously treated locally advanced or metastatic non-small cell lung cancer (NSCLC) for whom prior platinum therapy has failed. The study enrolled 371 patients. The study met its primary endpoints, demonstrating comparable levels of Tecentriq in the blood during a given dosing interval on the basis of established pharmacokinetic measurements; observed serum Ctrough and model-predicted area under the curve. Efficacy, as measured by the overall response rate, progression-free survival, overall survival and duration of response, was similar between the SC and IV treatment arms and consistent with the known profile of Tecentriq IV. The safety profile of Tecentriq SC was also consistent with that of Tecentriq IV.6,8 Tecentriq® (atezolizumab) in Tecentriq SC is the same monoclonal antibody as in Tecentriq IV. It has been designed to bind with a protein called programmed death ligand-1 (PD-L1), which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells. Tecentriq is a cancer immunotherapy that has the potential to be used across a broad range of cancers. Tecentriq SC combines Tecentriq with Halozyme Therapeutics’ Enhanze® drug delivery technology. The Enhanze drug delivery technology is based on a proprietary recombinant human hyaluronidase PH20 (rHuPH20), an enzyme that locally and temporarily degrades hyaluronan – a glycosaminoglycan or chain of natural sugars in the body – in the subcutaneous space. This increases the permeability of the tissue under the skin, allowing space for Tecentriq to enter, enabling it to be rapidly dispersed and absorbed into the bloodstream. Tecentriq SC was first approved in Great Britain in August 2023. The approved indications for Tecentriq SC mirror those of Tecentriq IV. The standard IV formulation of Tecentriq is approved for some of the most aggressive and difficult-to-treat forms of cancer. Tecentriq IV was the first cancer immunotherapy approved for the treatment of a certain type of early-stage (adjuvant) NSCLC, small cell lung cancer (SCLC) and hepatocellular carcinoma (HCC). Tecentriq IV is also approved in countries around the world, either alone or in combination with targeted therapies and/or chemotherapies, for various forms of metastatic NSCLC, certain types of metastatic urothelial cancer (mUC), PD-L1-positive metastatic triple-negative breast cancer (TNBC), BRAF V600 mutation-positive advanced melanoma and alveolar soft part sarcoma (ASPS). To learn more about Roche’s scientific-led approach to cancer immunotherapy, please follow this link: https://www.roche.com/solutions/focus-areas/oncology/cancer-immunotherapy Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. In recognising our endeavour to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the fifteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. References [1] Rummel M, et al. Preference for subcutaneous or intravenous administration of rituximab among patients with untreated CD20+ diffuse large B-cell lymphoma or follicular lymphoma: results from a prospective, randomized, open-label, crossover study (PrefMab). Ann Oncol. 2017;28(4):836-842. [2] De Cock E, et al. A time and motion study of subcutaneous versus intravenous trastuzumab in patients with HER2-positive early breast cancer. Cancer Med. 2016;5(3):389-97. [3] O’Shaugnessy, J. Patient (pt) preference for the pertuzumab-trastuzumab fixed-dose combination for subcutaneous use (PH FDC SC) in HER2-positive early breast cancer (EBC): Primary analysis of the open-label, randomised crossover PHranceSCa study. Presented at ESMO; 19-21 Sept 2020. Abstract #165MO. [4] Pivot X, et al. Efficacy and safety of subcutaneous trastuzumab and intravenous trastuzumab as part of adjuvant therapy for HER2-positive early breast cancer: final analysis of the randomised, two-cohort PrefHer study. Eur J Cancer. 2017;86:82-90. [5] Denys H, et al. Safety and tolerability of subcutaneous trastuzumab at home administration, results of the phase IIIb open-label BELIS study in HER2-positive early breast cancer. Breast Cancer Res Treat. 2020;181(1):97-105. [6] Burotto M, Zvirbule Z, Alvarez R, et al. IMscin001 Part 2 updated results: Efficacy, safety, immunogenicity, healthcare provider perspectives and patient-reported outcomes from the randomised Phase III study of atezolizumab subcutaneous vs intravenous in patients with locally advanced or metastatic non-small cell lung cancer. Presented at ESMO; 23 October 2023. Poster #1447P. [7] European Medicines Agency. Tecentriq, INN-atezolizumab. SmPC. [Internet; last updated 25 July 2023; cited December 2023] Available from: https://www.ema.europa.eu/en/documents/product-information/tecentriq-epar-product-information_en.pdf. [8] Burotto M, Zvirbule Z, Mochalova A, et al. IMscin001 Part 2: a randomised phase III, open-label, multicentre study examining the pharmacokinetics, efficacy, immunogenicity, and safety of atezolizumab subcutaneous versus intravenous administration in previously treated locally advanced or metastatic non-small-cell lung cancer and pharmacokinetics comparison with other approved indications. Ann Oncol. 2023;34(8):693-702. The content above comes from the network. if any infringement, please contact us to modify.

Jan. 09, 2024 -- Shanghai Junshi Biosciences Co., Ltd (“Junshi Biosciences,” HKEX: 1877; SSE: 688180), a leading innovation-driven biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies, announced the publication of results from TORCHLIGHT (NCT04085276), a randomized, double-blind, placebo-controlled phase 3 study comparing the efficacy and safety of toripalimab versus placebo, in combination with nab-paclitaxel for patients with newly diagnosed metastatic or recurrent locally advanced triple-negative breast cancer (TNBC) in Nature Medicine. TORCHLIGHT is the first registered Phase 3 study to achieve positive results in advanced TNBC immunotherapy in China. It was jointly conducted across 56 centers nationwide, with principal investigator Professor Zefei JIANG from the Department of Oncology of the Chinese People’s Liberation Army General Hospital and Vice President and Secretary General of the Chinese Society of Clinical Oncology (CSCO). “Using immunotherapy with Chinese products and designs to address the challenges of Chinese patients with advanced TNBC, TORCHLIGHT has produced encouraging results, providing some TNBC patients with an opportunity at prolonged survival,” said Professor Zefei JIANG. From December 25, 2018, to November 30, 2022, 531 patients were enrolled and randomized at a 2:1 ratio into either the experimental arm (n = 353; treated with toripalimab and nab-paclitaxel) or the control arm (n = 178; treated with placebo and nab-paclitaxel). A total of 300 patients had PD-L1-positive TNBC: 200 in the toripalimab arm and 100 in the control arm. The primary endpoints were progression-free survival (PFS), as assessed by blinded independent central review (BICR) per RECIST v.1.1, in the PD-L1-positive subgroup and the intention-to-treat (ITT) population. The secondary endpoints included overall survival (OS) in the PD-L1-positive and ITT populations, 1-year and 2-year OS rates, PFS as assessed by the investigator, objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety. TORCHLIGHT’s results show that the addition of toripalimab to nab-paclitaxel significantly improved PFS for PD-L1-positive patients with metastatic or recurrent TNBC, while maintaining an acceptable safety profile. At the prespecified interim analysis (cutoff date of 30 November 2022), a statistically significant improvement in PFS assessed by BICR was demonstrated in the toripalimab arm in the PD-L1-positive population (median PFS 8.4 versus 5.6 months; hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.470–0.906, P = 0.0102), which had crossed the prespecified efficacy boundary of 0.0273. The 1-year PFS rate was 41.9% versus 24.4%, and the 2-year PFS rate was 23.5% versus 14.5%. The interim analysis of PFS in the ITT population showed a similar improvement in BICR-assessed PFS. The median PFS was 8.4 and 6.9 months for the toripalimab and control arms, respectively, and the HR was 0.77 (95% CI 0.602–0.994), P = 0.0445. According to the prespecified descriptive analysis of OS, a trend toward improved OS favoring toripalimab was observed in the PD-L1-positive population, with median OS at 32.8 versus 19.5 months (HR = 0.62, 95% CI 0.414–0.914, nominal P = 0.0148). The 1, 2 and 3-year OS rates in the PD-L1-positive population were 82.6% versus 73.0%, 64.6% versus 43.5% and 47.9% versus 33.0% in the two arms, respectively. Similar OS improvement was also observed in the ITT population favoring toripalimab, with median OS 33.1 versus 23.5 months (HR = 0.69, 95% CI 0.513–0.932, nominal P = 0.0145). The 1, 2 and 3-year OS rates in the ITT population were 81.0% versus 77.6%, 61.0% versus 47.2% and 48.4% versus 32.1% in the two arms, respectively. Patients in the toripalimab arm had a significantly longer DoR than those in the control arm in the PD-L1-positive subgroup and ITT populations. The median DoR was 10.8 versus 5.6 months (HR = 0.55, 95% CI 0.366–0.830, nominal P = 0.0040) in the PD-L1-positive subgroup; and 8.5 versus 6.9 months (HR 0.64, 95% CI 0.468–0.881, nominal P = 0.0060) in the ITT population. Similar incidences of treatment-emergent adverse events (AEs) (99.2% versus 98.9%), grade ≥3 treatment-emergent AEs (56.4% versus 54.3%) and fatal AEs (0.6% versus 3.4%) occurred in the toripalimab and control arms. In May 2023, the supplemental new drug application (sNDA) for toripalimab in combination with albumin-bound paclitaxel for the treatment of PD-L1 positive (CPS ≥ 1) previously-untreated metastatic or recurrent metastatic TNBC was accepted by the National Medical Products Administration (NMPA). “I am delighted to see the TORCHLIGHT study reach new heights once again,” said Dr. Jianjun ZOU, Global Research and Development President of Junshi Biosciences. “TORCHLIGHT’s series of successes would not have been possible without the collaboration and determination of the patients, researchers, and R&D team. The groundbreaking outcomes of this study has the potential to address unmet clinical needs and offer Chinese TNBC patients better treatment options.” Toripalimab is an anti-PD-1 monoclonal antibody developed for its ability to block PD-1 interactions with its ligands, PD-L1 and PD-L2, and for enhanced receptor internalization (endocytosis function). Blocking PD-1 interactions with PD-L1 and PD-L2 promotes the immune system’s ability to attack and kill tumor cells. More than forty company-sponsored toripalimab clinical studies covering more than fifteen indications have been conducted globally by Junshi Biosciences, including in China, the United States, Southeast Asia, and Europe. Ongoing or completed pivotal clinical trials evaluating the safety and efficacy of toripalimab cover a broad range of tumor types, including cancers of the lung, nasopharynx, esophagus, stomach, bladder, breast, liver, kidney, and skin. In China, toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing (approved in China as TUOYI®). Currently, there are seven approved indications for toripalimab in China: unresectable or metastatic melanoma after failure of standard systemic therapy; recurrent or metastatic nasopharyngeal carcinoma (“NPC”) after failure of at least two lines of prior systemic therapy; locally advanced or metastatic urothelial carcinoma that failed platinum-containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy; in combination with cisplatin and gemcitabine as the first-line treatment for patients with locally recurrent or metastatic NPC; in combination with paclitaxel and cisplatin in first-line treatment of patients with unresectable locally advanced/recurrent or distant metastatic esophageal squamous cell carcinoma (ESCC); in combination with pemetrexed and platinum as the first-line treatment in EGFR mutation-negative and ALK mutation-negative, unresectable, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC); in combination with chemotherapy as perioperative treatment and subsequently with monotherapy as adjuvant therapy for the treatment of adult patients with resectable stage IIIA-IIIB NSCLC. The first six indications have been included in the National Reimbursement Drug List (NRDL) (2023 Edition). Toripalimab is the only anti-PD-1 monoclonal antibody included in the NRDL for the treatment of melanoma. In the United States, the U.S. Food and Drug Administration (FDA) has approved the Biologics License Application for toripalimab in combination with cisplatin and gemcitabine for the first-line treatment of adults with metastatic or recurrent locally advanced NPC, and for toripalimab, as a single agent, for the treatment of adults with recurrent, unresectable, or metastatic NPC with disease progression on or after platinum-containing chemotherapy in October 2023. The FDA has granted toripalimab 2 Breakthrough Therapy designations for the treatment of NPC, 1 Fast Track designation for the treatment of mucosal melanoma, and 5 Orphan Drug designations for the treatment of esophageal cancer, NPC, mucosal melanoma, soft tissue sarcoma, and small cell lung cancer (SCLC). In Europe, marketing authorization applications (MAA) were accepted by the European Medicines Agency (EMA) and the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) for 1) toripalimab combined with cisplatin and gemcitabine for the first-line treatment of patients with locally recurrent or metastatic NPC and 2) toripalimab combined with paclitaxel and cisplatin for the first-line treatment of patients with unresectable locally advanced/recurrent or metastatic ESCC, in December 2022 and February 2023. In Australia, the new chemical entity (NCE) application was accepted by the Australia Therapeutic Goods Administration (TGA) in November 2023. The TGA has also granted toripalimab an Orphan Drug designation for the treatment of NPC. Founded in December 2012, Junshi Biosciences (HKEX: 1877; SSE: 688180) is an innovation-driven biopharmaceutical company dedicated to the discovery, development and commercialization of innovative therapeutics. The company has established a diversified R&D pipeline comprising over 50 drug candidates, with five therapeutic focus areas covering cancer, autoimmune, metabolic, neurological, and infectious diseases. Four of the company’s innovations have already reached the Chinese or international markets, one of which is toripalimab, China’s first domestically produced and independently developed anti-PD-1 monoclonal antibody, approved in China and the US. Additionally, more than 30 drugs are currently in clinical development. During the COVID-19 pandemic, Junshi Biosciences actively shouldered the social responsibilities of a Chinese pharmaceutical company through its involvement in developing etesevimab, MINDEWEI®, and other novel therapies for the prevention and treatment of COVID-19. With a mission of “providing patients with world-class, trustworthy, affordable, and innovative drugs”, Junshi Biosciences is “In China, For Global.” At present, the company boasts approximately 3,000 employees in the United States (San Francisco and Maryland) and China (Shanghai, Suzhou, Beijing, Guangzhou, etc). For more information, please visit: http://junshipharma.com. The content above comes from the network. if any infringement, please contact us to modify.