Choroid Plexus Papilloma

The independent Data and Safety Monitoring Board (DSMB) recommended the continuation of patient enrollment as planned. There has been no safety concern with the use of Leuprolide (FP-001) injectable Emulsion in pediatric CPP patients. TAIPEI, April 1, 2024 /PRNewswire/ -- Foresee Pharmaceuticals (TPEx: 6576), ("Foresee") today announces the positive safety review by the independent Data and Safety Monitoring Board for its Casppian Phase 3 registration study. The DSMB recommended that Foresee Pharmaceuticals continue the trial with a minor amended protocol. The Casppian Phase 3 study is an open-label, multicenter, multinational clinical trial to evaluate the efficacy, safety, and pharmacokinetics of Leuprolide (FP-001) 42 mg-controlled release in patients with central (Gonadotropin-Dependent) precocious puberty (CPP). Foresee's Leuprolide injectable emulsion, 42 mg (marketed under the brand name CAMCEVI®), is currently approved for the treatment of adult patients with advanced prostate cancer and has demonstrated positive efficacy and safety results with statistically significant treatment effects in adult male patients with advanced prostate cancer. "We are pleased to receive the positive recommendation from the DSMB to continue our clinical trial. Ensuring the safety of the children participating in our trial is paramount and we continue to be dedicated to maintaining the highest standards of safety and ethical conduct throughout this clinical trial. The top-line results from this trial are anticipated in 2025.", said Bassem Elmankabadi, M.D., Senior Vice President of Clinical Development at Foresee Pharmaceuticals. "Foresee's Leuprolide 42 mg formulation (FP-001) dosed subcutaneously every 6 months, has the potential to become the only ready-to-use Leuprolide 6-month long-acting injection on the market, providing benefit to stakeholders in the CPP community. This positive recommendation brings us closer to our goal of delivering safe and effective treatment for children in need," said Dr. Ben Chien, Foresee's Chairman and CEO. "We look forward to establishing commercial partnership soon for the potential future commercialization of FP-001, in CPP indication." About CPP GnRH-dependent CPP is a condition that causes early sexual development in girls and boys, as their "hypothalamus - pituitary gland - gonadal axis" is activated too early, causing children to enter puberty prematurely, between 2 years and 9 years of age. CPP patients are at risk of having significantly short stature as adults in addition to social, psychological, and emotional issues, including lower self-esteem, stress, anxiety, and depression, which may negatively impact their quality of life. According to the NORD (National Organization for Rare Disorders) website, CPP occurs in 1 out of 5,000 to 10,000 children. It is estimated that approximately 80% - 90% of CPP cases are idiopathic, especially in females, with a female-to-male ratio of around 20. Gonadotropin-releasing hormone (GnRH) agonists, including leuprolide, are the most widely used treatment for CPP. About Foresee Pharmaceuticals Co., Ltd. Foresee is a Taiwan and US-based biopharmaceutical company listed on the Taipei Exchange (TPEx: 6576). Foresee's R&D efforts are focused on two key areas, namely its unique Stabilized Injectable Formulation (SIF) long-acting injectable technology with derived drug products targeting specialty markets and secondly, its transformative preclinical and clinical first-in-class NCE programs targeting rare and severe disease areas with high unmet needs. Foresee's product portfolio includes late and early-stage programs. CAMCEVI® 42 mg, for the treatment of advanced prostate cancer, is now approved in the U.S., Canada, EU, and Taiwan and launched in the U.S. in April 2022. Additionally, U.S. and EU regulatory submissions are being prepared for CAMCEVI® 21 mg. The second indication of CAMCEVI® 42 mg – central precocious puberty (CPP), the Casppian phase 3 clinical study, has been initiated. FP-025 – a highly selective oral MMP-12 inhibitor targeting inflammatory and fibrotic diseases, a Phase 2 proof-of-concept study in allergic asthmatic patients has been completed with positive outcomes, with future development in rare immune-fibrotic diseases. FP-020, a follow-on oral MMP-12 inhibitor currently in Phase 1, with development targeted in severe asthma and COPD. FP-045 – a highly selective oral small molecule allosteric activator of ALDH2, a mitochondrial enzyme, for which the FuschiA Phase 1b/2 Fanconi Anemia study is currently being initiated, and a Phase 2 study in pulmonary hypertension-interstitial lung disease (PH-ILD) patients is in planning. SOURCE Foresee Pharmaceuticals Co., Ltd.

转载自：中山大学肿瘤防治中心儿童肿瘤科编者按目前，儿童肿瘤患者的标准治疗主要包括手术、化疗和放疗。令人遗憾的是，对于儿童实体瘤的预后仍然不容乐观，PD-1等新型免疫检查点抑制剂在儿童肿瘤的应用值得探索。国家一类创新药信迪利单抗率先针对儿童晚期及难治肿瘤进行了积极的尝试，探索儿童肿瘤免疫治疗的潜力。中山大学肿瘤防治中心张翼鷟教授团队在该方面的研究结果现已刊发国际权威期刊《Signal Transduction and Targeted Therapy》，研究显示，信迪利单抗不论是作为单一药物疗法还是与其他药物联合治疗的一部分，都为儿童肿瘤治疗提供了初步依据。近日，中山大学肿瘤防治中心张翼鷟教授团队在国际权威期刊《Signal Transduction and Targeted Therapy》（IF：39.3）在线发表了题为“信迪利单抗在儿童晚期或复发难治肿瘤中安全性及有效性的I期临床试验”的研究结果。儿童肿瘤患者的标准治疗主要包括手术、化疗和放疗。令人遗憾的是，对于儿童肿瘤患者中复发或晚期实体肿瘤的预后仍然不容乐观，免疫检查点抑制剂等新型治疗在儿童肿瘤的应用值得探索。KEYNOTE-051和ADVL1412研究PD1抗体在儿童肿瘤中的疗效，但在亚洲儿童人群中，PD-1抗体的前瞻性研究非常有限。Pembrolizumab和Nivolumab等药物因为费用高昂阻碍了它们在国内的广泛应用，导致儿童肿瘤领域国内PD-1抗体数据的巨大空白。本研究首次探索了国产PD-1抗体信迪利单抗治疗儿童晚期及难治复发的肿瘤的安全性和有效性。研究纳入了29名受试者，分为三个递增剂量的队列：1 mg/kg、3 mg/kg和10 mg/kg。主要的研究目标包括确定剂量限制性毒性并评估治疗的安全性和耐受性。次要研究终点包括客观反应率（ORR）、无进展生存期（PFS）以及总生存期（OS）。受试者的临床病理类型包括除了霍奇金淋巴瘤以外，也包括一些罕见的儿童肿瘤病理亚型，例如原发性纵隔大B细胞淋巴瘤， NK/T细胞淋巴瘤，恶性间皮瘤，间叶原性恶性肿瘤，间变室管膜瘤，上皮样肉瘤，胸腺瘤，卵黄囊瘤，非典型脉络丛乳头状瘤等。安全性方面，信迪利单抗耐受性表现良好，29名患者中有89.7%患者至少出现一种治疗相关不良事件。包括：贫血（34.5%）；疲劳（6.9%）；甲状腺功能减退（17.2%）；甲状腺功能亢进（13.8%）等。3名患者（10.3%）出现了三级以上的治疗相关不良反应，包括转移酶升高和肌炎，以及血小板计数降低。安全数据没有显示出剂量（1-10 mg/kg）相关的特征。未发生治疗相关的严重不良事件（SAEs）。疗效方面，霍奇金淋巴瘤患者中，总体ORR和DCR分别为60.0%和100%，20%患者最佳疗效为CR。在除霍奇金淋巴瘤以外的肿瘤中观察到2例CR（NK/T细胞淋巴瘤和间变室管膜瘤），3例PR（包括1例弥漫性大B细胞淋巴瘤、1例尤文肉瘤和1例胸腺瘤）3例SD (包括1例上皮样肉瘤、1例非典型脉络丛乳头状瘤和1例原发性纵隔大B细胞淋巴瘤）ORR 为29.4%，DCR 为47.1%。另外，对患儿的肿瘤标本进行外显子测序结果发现G 蛋白偶联受体 (GPCR) 是参与信号传递的最大的细胞膜相关分子基因家族，与治疗抵抗和免疫逃避有关，结果表明对 免疫检查点抑制剂的无反应与 GPCR 途径的激活有关。使用WES对受试者的FFPE肿瘤和匹配的外周血样本进行基因组分析综上，研究结果显示信迪利单抗在儿童中的耐受性良好。虽然在这项研究中，信迪利单抗在大多数儿童实体瘤中并未表现出明显的单药疗效，但观察到了对霍奇金淋巴瘤的抗肿瘤活性。这一研究为未来进一步探讨PD-1/PD-L1抑制剂在儿童肿瘤治疗中的潜力，不论是作为单一药物疗法还是与其他药物联合治疗的一部分，提供了初步依据。中山大学肿瘤防治中心张翼鷟教授、路素英副教授为本研究的共同通讯作者。中山大学肿瘤防治中心阙旖医师、王娟主治医师，孙斐斐主治医师以及重庆医科大学附属儿童医院王珊教授是本研究的共同第一作者。文献：Yi Que, Juan Wang, Feifei Sun, Shan Wang, Jia Zhu, Junting Huang, Zhenzhen Zhao, Li Zhang, Juan Liu1, Jiaqian Xu,Zijun Zhen, Xiaofei Sun, Suying Lu1 and Yizhuo Zhang. Safety and clinical efficacy of sintilimab (anti-PD-1) in pediatric patients with advanced or recurrent malignancies in a phase I study. Signal Transduction and Targeted Therapy (2023) 8:392 . https://doi.org/10.1038/s41392-023-01636-9.点击蓝字 阅读原文

这项1期临床研究结果显示信迪利单抗在儿童中的耐受性良好。虽然在这项研究中，信迪利单抗在大多数儿童实体瘤中并未表现出明显的单药疗效，但观察到了对霍奇金淋巴瘤的抗肿瘤活性。 中山大学肿瘤防治中心张翼鷟教授团队在 Signal Transduction and Targeted Therapy 期刊发表了题为：Safety and clinical efficacy of sintilimab (anti-PD-1) in pediatric patients with advanced or recurrent malignancies in a phase I study（信迪利单抗在儿童晚期或复发难治肿瘤中安全性及有效性的I期临床试验）的研究论文。 该研究首次探索了国产PD-1抗体信迪利单抗（Sintilimab）治疗儿童晚期及难治复发的肿瘤的安全性和有效性。 该研究纳入了29名受试者，分为三个递增剂量的队列：1 mg/kg、3 mg/kg和10 mg/kg。主要的研究目标包括确定剂量限制性毒性并评估治疗的安全性和耐受性。次要研究终点包括客观反应率（ORR）、无进展生存期（PFS）以及总生存期（OS）。受试者的临床病理类型包括除了霍奇金淋巴瘤以外，也包括一些罕见的儿童肿瘤病理亚型，例如原发性纵隔大B细胞淋巴瘤， NK/T细胞淋巴瘤，恶性间皮瘤,，间叶原性恶性肿瘤，间变室管膜瘤，上皮样肉瘤，胸腺瘤，卵黄囊瘤，非典型脉络丛乳头状瘤等。 安全性方面，信迪利单抗耐受性表现良好，29名患者中有89.7%患者至少出现一种治疗相关不良事件。包括：贫血（34.5%）；疲劳（6.9%）；甲状腺功能减退（17.2%）；甲状腺功能亢进（13.8%）等。3名患者（10.3%）出现了三级治疗相关不良反应，包括转移酶升高和肌炎，以及血小板计数降低。安全数据没有显示出剂量（1-10 mg/kg）相关的特征。未发生治疗相关的严重不良事件（SAEs）。 疗效方面，霍奇金淋巴瘤患者中，总体ORR和DCR分别为60.0%和100%，20%患者最佳疗效为CR。在除霍奇金淋巴瘤以外的肿瘤中观察到2例CR（NK/T细胞淋巴瘤和间变室管膜瘤），3例PR（包括1例弥漫性大B细胞淋巴瘤、1例尤文肉瘤和1例胸腺瘤），3例SD（包括1例上皮样肉瘤、1例非典型脉络丛乳头状瘤和1例原发性纵隔大B细胞淋巴瘤）ORR 为29.4%，DCR 为47.1%。 另外，对患儿的肿瘤标本进行外显子测序结果发现G蛋白偶联受体（GPCR）是参与信号传递的最大的细胞膜相关分子基因家族，与治疗抵抗和免疫逃避有关，结果表明对免疫检查点抑制剂的无反应与GPCR通路的激活有关。 使用全外显子测序对受试者的FFPE肿瘤和匹配的外周血样本进行基因组分析 综上，这项1期临床研究结果显示信迪利单抗在儿童中的耐受性良好。虽然在这项研究中，信迪利单抗在大多数儿童实体瘤中并未表现出明显的单药疗效，但观察到了对霍奇金淋巴瘤的抗肿瘤活性。这一研究为未来进一步探讨PD-1/PD-L1抑制剂在儿童肿瘤治疗中的潜力，不论是作为单一药物疗法还是与其他药物联合治疗的一部分，提供了初步依据。