A Multicenter, Open-label, Single-arm, Phase II Clinical Trial to Evaluate the Preventive Effect of Pegylated G-CSF (PG) on Neutropenia in Patients With Metastatic Triple-negative Breast Cancer (mTNBC) Receiving Sacituzumab Govitecan (SG)

Prevention of Sacituzumab Govitecan-related Neutropenia in Patients with metastatic Triple Nagative Breast Cancer who have received at least one, and no more than two, prior standard of care chemotherapy regimens

开始日期2024-12-01

申办/合作机构

Samsung Medical Center

NCT05741164 / Not yet recruiting临床2期IIT

Impact of Beta-2 Adrenergic Blockade With Checkpoint Inhibition in Checkpoint Inhibitor Refractory Metastatic Triple Negative Breast Cancer

This phase II trial tests how well propranolol and pembrolizumab work to cause tumor re-sensitization and therefore treatment in patients with triple negative breast cancer that has not responded to previous checkpoint inhibitor therapy (refractory), cannot be removed by surgery (unresectable) or has spread from where it first started (primary site) to other places in the body (metastatic). Propranolol is a drug that is classified as a beta-blocker. Beta-blockers affect the heart and circulation. Beta-blockers, like propranolol, may help to counteract effects of certain stress hormones produced by the body during cancer treatment and may increase the effectiveness of the pembrolizumab. Pembrolizumab is a drug that is classified as an immune checkpoint inhibitor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Propranolol may be able to re-sensitize the cells of the immune system to respond to the checkpoint inhibitor pembrolizumab in patients with checkpoint inhibitor refractory metastatic or unresectable triple negative breast cancer.

开始日期2024-11-30

申办/合作机构

Roswell Park Comprehensive Cancer Center

NCT06434064 / Not yet recruiting临床2期IIT

A Pilot, Single-Arm, Phase II Trial of Tamoxifen Plus Pegylated Liposomal Doxorubicin in Patients With Metastatic Triple Negative Breast Cancer

This phase II trial tests how well tamoxifen and pegylated liposomal doxorubicin works in treating patients with triple negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or that has spread to nearby tissue or lymph nodes (locally advanced) and is unable to be operated on (inoperable). Tamoxifen works by blocking the effects of estrogen in the breast. This may help stop the growth of tumor cells that need estrogen to grow. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair. Liposomal doxorubicin is a form of the anticancer drug doxorubicin that is contained inside very tiny, fat-like particles. Liposomal doxorubicin may have fewer side effects and work better than other forms of the drug. Giving tamoxifen and pegylated liposomal doxorubicin together may work better in treating patients with metastatic or inoperable, locally advanced triple negative breast cancer than giving either of these drugs alone.

开始日期2024-11-30

申办/合作机构

Roswell Park Comprehensive Cancer Center

100 项与转移性三阴性乳腺癌相关的临床结果

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100 项与转移性三阴性乳腺癌相关的转化医学

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0 项与转移性三阴性乳腺癌相关的专利（医药）

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560

项与转移性三阴性乳腺癌相关的文献（医药）

2024-11-01·International Journal of Clinical Oncology

Preliminary results from ASCENT-J02: a phase 1/2 study of sacituzumab govitecan in Japanese patients with advanced solid tumors

Article

作者: Kogawa, Takahiro ; Iwata, Hiroji ; Lai, Catherine ; Zhang, Danjie ; Nakayama, Takahiro ; Matsumoto, Koji ; Ishida, Takanori ; Yamamoto, Yutaka ; Gary, Dianna ; Sudo, Kazuki ; Masuda, Norikazu ; Huynh, Danh ; Kawaguchi-Sakita, Nobuko ; Naito, Yoichi ; Shimomura, Akihiko ; Nakamura, Seigo ; Iwahori, Yuki

AbstractBackgroundSacituzumab govitecan (SG) is a Trop-2–directed antibody–drug conjugate approved outside Japan for second-line and later metastatic triple-negative breast cancer (mTNBC), based on the ASCENT study (NCT02574455). We report SG safety and efficacy in an open-label, phase 1/2 bridging study in Japanese patients with advanced solid tumors (ASCENT-J02; NCT05101096; jRCT2031210346).MethodsPhase 1 was a standard 3 + 3 design. Patients received intravenous SG 6 mg/kg, escalating to 10 mg/kg, on Days 1 and 8 per 21-day cycle; primary endpoints were safety, incidence of dose-limiting toxicity/toxicities (DLTs), and determination of the recommended phase 2 dose (RP2D). In the multicohort phase 2 study, patients in the mTNBC cohort with previously treated disease received SG at the RP2D; primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR; RECIST v1.1). Safety was a secondary endpoint.ResultsIn phase 1 (N = 15), one DLT (grade 3 elevated transaminases) occurred with SG 10 mg/kg; RP2D was SG 10 mg/kg regardless of UGT1A1 status. In phase 2, 36 patients with mTNBC received SG 10 mg/kg. At median follow-up of 6.1 months, IRC-assessed ORR was 25.0% (95% CI 12.1–42.2; P = 0.0077). Median progression-free survival was 5.6 months (95% CI 3.9–not reached [NR]); median overall survival was NR. No treatment-emergent adverse events led to discontinuation or death.ConclusionsSG RP2D was established as 10 mg/kg in Japanese patients. SG showed efficacy in Japanese patients with previously treated mTNBC, a manageable safety profile, and no new safety signals, consistent with the previous ASCENT study.

2024-11-01·Journal of Clinical Oncology

Prevalence, Dynamics, and Prognostic Role of Clonal Hematopoiesis of Indeterminate Potential in Patients With Breast Cancer

Article

作者: Weeks, Lachelle D. ; King, Tari A. ; Tayob, Nabihah ; Merrill, Margaret ; Santos, Katheryn ; Morganti, Stefania ; Tolaney, Sara M. ; Lin, Nancy U. ; Mittendorf, Elizabeth A. ; Lipsyc-Sharf, Marla ; Hughes, Melissa E. ; Stokes, Samantha ; Parsons, Heather A. ; Garber, Judy E. ; Curigliano, Giuseppe ; Wilson, Alex ; Parker, Tonia ; Patel, Ashka ; Vincuilla, Julie ; Stover, Daniel G. ; Jin, Qingchun ; Miller, Peter G. ; Gibson, Christopher J.

PURPOSEClonal hematopoiesis of indeterminate potential (CHIP) is frequent in patients with solid tumors. Prospective data about CHIP prevalence at breast cancer diagnosis and its dynamic evolution under treatment selective pressure are limited.PATIENTS AND METHODSWe performed targeted error-corrected sequencing on 614 samples from 380 patients with breast cancer. We investigated the dynamics of CHIP on prospectively collected paired samples from patients with early breast cancer (eBC) receiving chemotherapy (CT) or endocrine therapy (ET). We assessed the correlation of CHIP with survival in patients with metastatic triple-negative breast cancer (mTNBC). We estimated the risk of progression to treatment-related myeloid neoplasms (t-MN) according to the clonal hematopoiesis risk score (CHRS). In exploratory analyses, we considered clonal hematopoiesis (CH) with variant allele fraction (VAF) ≥0.005.RESULTS CHIP was identified in 15% of patients before treatment. Few CHIP emerged after treatment, and the risk of developing new mutations was similar for patients receiving CT versus ET (odds ratio [OR], 1.16; P = .820). However, CT increased the risk of developing new CH with VAF ≥0.005 (OR, 3.45; P = .002). Five TP53- mutant CH with VAF ≥0.005 emerged among patients receiving CT. Most patients had low risk of t-MN according to the CHRS score. CHIP did not correlate with survival in mTNBC. CONCLUSION CHIP is frequent in patients with breast cancer. In this study, CT did not lead to emergence of new CHIP, and most patients had low risk of developing t-MN. This finding is reassuring, given long life expectancy of patients with eBC and the association of CHIP with morbidity and mortality. However, TP53 -mutant CH with VAF ≥0.005 emerged with CT, which carries high risk of t-MN. Evolution of these small clones and their clinical significance warrant further investigation.

2024-11-01·Journal of Controlled Release

Synergistic anticancer immunity in metastatic triple-negative breast cancer through an in situ amplifying Peptide-Drug Conjugate

Article

作者: Ko, Yoon Gun ; Kim, Ha Rin ; Park, Seong Jin ; Kim, Sang Yoon ; Byun, Youngro ; Cho, Young Seok

Despite significant progress in combining cancer immunotherapy with chemotherapy to treat triple negative breast cancer (TNBC), challenges persist due to target depletion and tumor heterogeneity, especially in metastasis. Chemotherapy lacks precise targeting abilities, and targeted therapy is inadequate in addressing the diverse heterogeneity of tumors. To address these challenges, we introduce RGDEVD-DOX as a tumor-specific immunogenic agent, namely TPD1, which targets integrin αvβ3 and gets continuously activated by apoptosis. TPD1 facilitates the caspase-3-mediated in situ amplification that results in tumor-specific accumulation of doxorubicin. This local concentration of doxorubicin induces immunogenic cell death and promotes the recruitment of immune cells to the tumor site. Notably, the tumor-targeting capabilities of TPD1 help bypass the systemic immunotoxicity of doxorubicin. Consequently, this alters the tumor microenvironment, converting it into a 'hot' tumor that is more susceptible to immune checkpoint inhibition. We demonstrated the anti-metastatic and anti-cancer efficacy of this treatment using various xenograft and metastatic models. This study underscores the high potential of caspase-3 cleavable peptide-drug conjugates to be used in conjunction with anti-cancer immunotherapies.

389

项与转移性三阴性乳腺癌相关的新闻（医药）

2024-10-31

·药研网

科伦博泰 TROP2 ADC 新药第3项适应症申报上市

10月31日，CDE官网最新公示，科伦博泰申报的注射用芦康沙妥珠单抗新适应症上市申请获得受理。根据科伦博泰公告介绍，本次申报上市的适应症为：用于经表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）治疗后进展的EGFR突变局部晚期或转移性非小细胞肺癌成人患者。这是芦康沙妥珠单抗(sac-TMT)获NMPA受理的第三个NDA。该申请已于日前被CDE拟纳入优先审评。 OptiTROP-Lung04是一项多中心、随机、注册III期临床研究，评估芦康沙妥珠单抗(sac-TMT)单药对比培美曲塞联合铂类治疗经EGFR-TKI治疗后进展的EGFR突变局部晚期或转移性NSCLC患者中的疗效和安全性。在预设的期中分析中，与培美曲塞联合铂类相比，芦康沙妥珠单抗(sac-TMT)单药在主要研究终点盲态独立评审委员会（BICR）评估的无进展生存期(PFS)具有显著统计学意义和临床意义的改善。 2024年美国癌症研究协会（AACR）年会上，研究人员公布了芦康沙妥珠单抗用于既往接受过治疗的晚期非小细胞肺癌（NSCLC）患者的2期研究的最新疗效和安全性结果。结果显示，在EGFR突变型NSCLC患者亚组（既往接受EGFR-TKI治疗期间或之后病情有所进展且其中50%的患者至少经历过1L化疗失败）中，芦康沙妥珠单抗的客观缓解率（ORR）为60%，中位无进展生存期（PFS）为11.5个月，中位总生存期（OS）为22.7个月。芦康沙妥珠单抗(sac-TMT)的安全性良好，未发现新的安全性信号。此前，芦康沙妥珠单抗(sac-TMT)两项NDA已获NMPA受理。分别用于既往至少接受过2种系统治疗（其中至少1种治疗针对晚期或转移性阶段）的局部晚期或转移性三阴性乳腺癌(TNBC)患者单药治疗接受EGFR-TKI和含铂化疗治疗失败的局部晚期或转移性EGFR突变NSCLC成人患者芦康沙妥珠单抗 (sac-TMT)是科伦博泰与默沙东（MSD）联合开发的一款靶向TROP-2的抗体偶联药物（ADC），靶向NSCLC、乳腺癌(BC)、胃癌(GC)、妇科肿瘤等晚期实体瘤。科伦博泰首席执行官葛均友博士表示“非常高兴芦康沙妥珠单抗（sac-TMT）再获第三项NDA。相信芦康沙妥珠单抗将在肿瘤领域大放异彩，为全球健康事业贡献中国力量”。 End 声明：本公众号所有发文章(包括原创及转载文章)系出于传递更多信息之目的，且注明来源和作者。本公众号欢迎分享朋友圈或大群，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载/商务/投稿 | 联系微信15618157102（sum_Gmi）商务合作稿件征集点击了解详情往期回顾 1 8月 | 高达22家药企裁员 2 国产首款四价HPV疫苗拟纳入优先审评 3 3. 7亿美元!今年规模最大的生物医药融资诞生

优先审批AACR会议临床3期申请上市抗体药物偶联物

2024-10-31

·Insight数据库

今日，科伦博泰 TROP2 ADC 第 3 项适应症申报上市

10 月 31 日，科伦博泰 TROP2 ADC「芦康沙妥珠单抗」递交了第三个适应症的上市申请，用于治疗经 EGFR-TKI 治疗失败的局部晚期或转移性 EGFR 突变非小细胞肺癌（NSCLC）成人患者。该申请已于日前被 CDE 纳入拟优先审评。截图来源：CDE 官网芦康沙妥珠单抗是一种靶向 TROP2 ADC。TROP2 在多种癌症中过表达，尤其是乳腺癌、NSCLC 等癌种。默沙东已获得科伦博泰授权，在海外研发、生产与商业化芦康沙妥珠单抗。芦康沙妥珠单抗此前已在国内递交了两项适应症上市申请，分别为：用于既往至少接受过 2 种系统治疗的不可切除的局部晚期或转移性三阴性乳腺癌成人患者（23 年 12 月申报，CXSS2300093），预测有望在今年 Q4 获批。用于治疗经 EGFR-TKI 和含铂化疗治疗失败的局部晚期或转移性 EGFR 突变 NSCLC（今年 8 月申报，CXSS2400087），预测有望明年 Q3 获批。芦康沙妥珠单抗本次的新适应症申请是基于注册性 III 期临床研究 OptiTROP-Lung04 的结果。该研究评估了芦康沙妥珠单抗单药治疗经 EGFR-TKI 治疗后进展的 EGFR 突变局部晚期或转移性 NSCLC 患者的疗效和安全性，对照组为培美曲塞联合铂类。预设的期中分析结果显示，与对照组相比，芦康沙妥珠单抗单药在主要研究终点—— BICR 评估的无进展生存期 (PFS) 方面，显示出具有显著统计学意义和临床意义的改善；同时，安全性良好。此前，科伦博泰曾在 2024 年 AACR 会议上公布了芦康沙妥珠单抗治疗 EGFR 突变局部晚期或转移性 NSCLC 成人患者的 2 期研究最新结果。截至数据截止日期（2023 年 11 月 22 日），43 例 NSCLC 患者入组，中位随访时间为 17.2 个月。其中，包括 22 例 EGFR 突变患者，这些患者在接受 TKI 治疗期间或之后病情有所进展，其中 50% 的患者至少经历了一线化疗失败。数据显示，在 EGFR 突变 NSCLC 患者中，ORR 为 60%，中位持续缓解时间为 8.7 个月，中位无进展生存期为 11.5 个月，中位总生存期为 22.7 个月，12 个月总体生存率为 81.0%，18 个月总体生存率为 76.2%。科伦博泰成立于 2016 年，现已建立包含 10 余款临床阶段候选药物的产品管线。这些产品的适应症以肿瘤居多。少数产品针对的是非肿瘤适应症，包括类风湿性关节炎、尿毒症瘙痒等。截图来源：Insight 数据库目前，科伦博泰已有 4 款产品在国内申报上市。除了芦康沙妥珠单抗外，还包括：博度曲妥珠单抗：HER2 ADC，23 年 5 月申报上市，用于治疗 HER2 阳性乳腺癌；塔戈利单抗：PD-L1 单抗，已在国内申报两项 NDA，分别用于鼻咽癌三线治疗（21 年 11 月申报）和鼻咽癌一线治疗（24 年 5 月申报）； A140：靶向 EGFR 的单抗，西妥昔单抗生物类似药，23 年 10 月申报上市，用于一线治疗 RAS 野生型转移性结直肠癌患者。不难看出，随着创新药的陆续申报上市，科伦博泰将逐渐迎来产品收获期。封面来源：企业 Logo 免责声明：本文仅作信息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。编辑：馨药 PR 稿对接：微信 insightxb 投稿：微信 insightxb；邮箱 insight@dxy.cn 多样化功能、可溯源数据…… Insight 数据库网页版等你体验点击阅读原文，立刻解锁！

AACR会议抗体药物偶联物优先审批临床结果申请上市

2024-10-31

·Pharma CMC

科伦博泰「芦康沙妥珠单抗」上市申请获受理，治疗NSCLC

10月30日，科伦博泰发布公告，公司核心产品芦康沙妥珠单抗基于OptiTROP-Lung04关键III期研究积极结果的新药申请已获CDE受理，用于治疗经表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)治疗后进展的EGFR突变局部晚期或转移性非小细胞肺癌(NSCLC)成人患者。 OptiTROP-Lung04是一项多中心、随机、注册Ⅲ期临床研究，评估芦康沙妥珠单抗(sac-TMT)单药对比培美曲塞联合铂类治疗经EGFR-TKI治疗后进展的EGFR突变局部晚期或转移性NSCLC患者中的疗效和安全性。在预设的期中分析中，与培美曲塞联合铂类相比，芦康沙妥珠单抗(sac-TMT)单药在主要研究终点盲态独立评审委员会（BICR）评估的无进展生存期（PFS）具有显著统计学意义和临床意义的改善。芦康沙妥珠单抗(sac-TMT)的安全性良好，未发现新的安全信号。本次新药申请是芦康沙妥珠单抗(sac-TMT)获NMPA受理的第三个NDA。2024年10月25日，CDE官网公布该申请拟纳入CDE的优先审评审批程序。此前，芦康沙妥珠单抗(sac-TMT)用于既往至少接受过2种系统治疗（其中至少1种治疗针对晚期或转移性阶段）的局部晚期或转移性三阴性乳腺癌(TNBC)患者以及单药治疗接受EGFR-TKI和含铂化疗治疗失败的局部晚期或转移性EGFR突变NSCLC成人患者的两项NDA已获NMPA受理。作为科伦博泰的核心产品，芦康沙妥珠单抗(sac-TMT)是一款科伦博泰拥有自主知识产权的新型人滋养层细胞表面抗原2(TROP2)抗体药物偶联物(ADC)，针对NSCLC、乳腺癌(BC)、胃癌(GC)、妇科肿瘤等晚期实体瘤。 2022年5月，科伦博泰授予默沙东（美国新泽西州罗威市默克公司的商号）在大中华区（包括中国内地、香港、澳门及台湾）以外的所有地区开发、使用、制造及商业化芦康沙妥珠单抗(sac-TMT)的独家权利。

优先审批临床3期抗体药物偶联物