Cyclophosphamide

10月24日，复旦大学附属肿瘤医院乳腺外科邵志敏教授、王中华教授、江一舟教授团队领衔的一项名为“BCTOP-T-A01”的研究成果证实：基于肿瘤医院自主研发的“多基因模型”，针对有“最毒乳腺癌”之称的三阴性乳腺癌，采用“蒽环紫杉”序贯“吉西他滨”联合“卡铂”的精准治疗方案，让高危患者生存率显著提升超过10%，改变了传统三阴性乳腺癌辅助化疗“千人一方”的局面。 这项研究成果于2024年10月24日，在《英国医学杂志》（The BMJ）正式发表。这也是复旦大学附属肿瘤医院产医融合发展的又一项标志性成果。 攻坚“最毒乳腺癌”治疗瓶颈 自主研发首个“多基因模型” 三阴性乳腺癌约占所有乳腺癌的15%-20%，因其恶性程度高、容易复发转移，相较于其他类型乳腺癌治疗手段单一、缺乏有效治疗靶点，素有“最毒乳腺癌”之称。近年来，越来越多的研究认为，三阴性乳腺癌具有极高的异质性，可以进一步被细分。在临床上也发现，虽然三阴性乳腺癌整体预后欠佳，但并非所有的患者都会出现复发转移的情况，更精准的治疗策略亟待探索。 然而，当前乳腺癌研究领域缺乏经过临床队列验证的针对三阴性乳腺癌特异的工具或模型，可用于精确地预测患者的复发转移风险，实现对患者风险分层进而开展个性化精准治疗。这也导致目前三阴性乳腺癌的辅助化疗只能沿用传统的“千人一方”的治疗方案。 因此，迫切需要一个通过前瞻性临床试验加以验证的模型，来优化三阴性乳腺癌的辅助治疗方案。2015年，复旦大学附属肿瘤医院邵志敏教授、江一舟教授团队基于全转录组表达谱，自主研发构建了由5个RNA组成的三阴性乳腺癌预后预测模型（后简称“多基因模型”），该模型可以准确地把三阴性乳腺癌患者划分为高危和低危复发风险组。这也是国际首个三阴性乳腺癌预后预测模型。相关研究成果发表于《癌症研究》（Cancer Research），为三阴性乳腺癌的精准化疗提供了理论依据。 “多基因模型开辟了三阴性乳腺癌精准治疗的新篇章”，肿瘤医院乳腺外科主任兼大外科主任邵志敏教授表示，“研究团队基于该模型，持续开展临床研究，致力将科研成果转化为真正让患者获益的方案。” 为了进一步验证“多基因模型”的预后效果并挖掘其临床应用价值，邵志敏教授领衔临床和转化团队开展了一项名为“BCTOP-T-A01”的临床研究。 高危患者生存率提升10.3% 重磅成果验证“多基因模型”价值 复旦大学附属肿瘤医院乳腺外科副主任王中华教授介绍，“BCTOP-T-A01”临床研究依托肿瘤医院精准肿瘤中心开展检测，由复旦肿瘤乳腺外科领衔全国其他六家中心具体开展协作临床研究。历时七年多，团队完成504位患者入组临床试验，入组患者均为接受根治性手术后的早期三阴性乳腺癌患者。 根据实验设计，研究团队依据入组患者的多基因模型检测结果，分为高危、低危组。其中，高危组患者按照1:1比例，随机接受强化或标准方案辅助化疗：强化组患者接受4个周期“多西他赛+表阿霉素+环磷酰胺”序贯4个周期“吉西他滨+顺铂（TEC*4-GP*4）”方案化疗；对照组患者接受4个周期“表阿霉素+环磷酰胺序贯4个周期多西他赛（EC*4-T*4）”方案。低危组患者同样接受标准方案化疗（EC*4-T*4）。 研究显示，经过中位45个月的随访，高危患者接受强化治疗组3年无病生存率为90.9%，显著优于标准治疗组的80.6%，绝对获益达到了10.3%，显著降低高危患者49%的疾病风险。其中，强化治疗组的3年无复发生存率（92.6%）也显著高于标准治疗组（83.2%），可以降低高危患者50%的复发风险；此外，低危患者的3年无病生存率（90.1%对比80.6%）、无复发生存率(94.5%对比83.2%)和总生存率(100%对比91.3%)均优于接受相同标准化疗方案的高危患者。 “这是一项令人振奋的研究成果，多基因模型知道的精准化疗方案让高危患者生存率提升超过了10%，低危患者的生存率提升也接近10%！”邵志敏教授说，“显著提升高危三阴性乳腺癌患者预后的同时，该治疗方案安全性可控，患者无严重不良反应，体现出该方案的更多优势。” 王中华教授表示，这项研究成果在国际上首次前瞻性验证了三阴性乳腺癌多基因模型指导精准化疗和预测患者预后的价值，为三阴性乳腺癌精准化疗奠定了坚实的理论基础并提供了有力工具。 “砺剑十载”破解临床难题 书写三阴性乳腺癌治疗“中国答卷” 据介绍，早在10年前，邵志敏教授领衔团队便开始致力于破解三阴性乳腺癌精准治疗难题。自主研发建立三阴性乳腺癌“多基因模型”；建立全球最大的三阴性乳腺癌多组学队列、绘制出全球最大的三阴性乳腺癌基因图谱，并开拓性的将三阴性乳腺癌分为四个分子亚型，提出“基于分子分型的三阴性乳腺癌精准治疗策略”；进一步开展临床研究，将三阴性乳腺癌的疗效提升3倍。在此基础上，研究团队还将研究思路拓展至其他乳腺癌亚型，形成了成熟的研究理论体系，大幅提高患者治疗效果，并产出多项具有国际影响力的研究成果和重要科研成果专利转化。 “多年来的研究成果使三阴性乳腺癌患者的辅助治疗更加精准和更有效，此次‘BCTOP-T-A01’研究的可喜成就，体现了系列研究从基础到临床的有效转化与衔接，为提升早期三阴性乳腺癌的治疗疗效、推动乳腺癌精准治疗做出了重要贡献。”邵志敏教授说，“该‘多基因模型’依托复旦肿瘤精准肿瘤中心开展临床检测，相关技术成果目前已经具备落地以及广泛推广的可行性，有望在更大范围内提升患者的治疗疗效。” 复旦大学附属肿瘤医院副院长、临床研究中心主任江一舟教授表示，“BCTOP-T-A01”也是邵志敏教授牵头成立的乳腺癌精准治疗协作组（BCTOP）开展的首个临床研究。多中心的合作模式和重磅成果，有力印证了“BCTOP”成立的宗旨——“基于精准医学理念，开展多中心临床研究，推广转化研究平台，开发新型药物和技术，最终提高我国乳腺癌诊治水平和国际地位。”基于“BCTOP-T-A01”的研究结果，肿瘤医院正准备开展针对模型预测的低危三阴性乳腺癌患者的降阶梯治疗。在不久的将来，“BCTOP”将向国际学术界不断交出亮眼的三阴性乳腺癌治疗“中国答卷”，以更多中国原创方案造福全球广大乳腺癌患者。 原文链接： https://shmc.fudan.edu.cn/news/2024/1028/c1892a142775/page.htm 本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

Testing the efficacy and safety of Intensity's lead drug candidate, INT230-6, when combined with Standard-of-Care versus Standard-of-Care alone The endpoint is the change in pathological complete response rates SHELTON, Conn. and BERN, Switzerland, Oct. 31, 2024 /PRNewswire/ -- Intensity Therapeutics, Inc. ("Intensity" or "the Company") (Nasdaq: INTS), a late-stage clinical biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumorally injected cancer therapies intended to kill tumors directly and increase immune system recognition of cancers, and The Swiss Group for Clinical Cancer Research SAKK ("SAKK"), a decentralized academic research institute that has been conducting clinical trials of cancer treatments in all major Swiss hospitals since 1965, are collaborating in the INVINCIBLE-4 Study, a Phase 2 trial to treat patients with localized triple-negative breast cancer ("TNBC"), and announce that the first patient has been dosed in the study. The trial (NCT06358573) analyzes INT230-6 given before administration of the standard-of-care neoadjuvant immuno-chemotherapy ("SOC") and the SOC alone by using a 2-cohort design. The study evaluates the pathological complete response ("pCR") rates of the two cohorts relative to a null hypothesis, which is a pCR rate of ≤ 0.6. The success of each cohort in rejecting the null hypotheses will be evaluated. The Phase 2 study is expected to enroll approximately 54 patients in Switzerland and France. The INVINCIBLE-4 Study is a randomized open-label, multicenter study to determine the clinical activity, safety, and tolerability of INT230-6 in patients with early-stage, operable TNBC who undergo SOC treatment and SOC alone. The primary endpoint is pCR in the primary tumor and affected lymph nodes. Patients will be randomized one to one to receive a regimen of either two doses of INT230-6 followed by SOC, which consists of pembrolizumab, anthracyclines, carboplatin, cyclophosphamide and paclitaxel, or to the SOC alone. The INVINCIBLE-4 Study initiation follows data reported from the Company's INVINCIBLE-2 Study, where INT230-6 given alone showed tumor-killing properties at levels greater than 95% on a single intratumoral dose with systemic immune activation. "Many TNBC patients undergoing SOC treatment alone fail to achieve a pathological complete response at the time of surgery, especially in larger tumor sizes. INT230-6 has the potential to fill this unmet need for aggressive subtypes, such as TNBC, through its anti-cancer mechanisms of action that cause tumor cell necrosis and ignite an anti-cancer immune-based response," said Andreas Mueller, M.D. Past-President of the Breast Cancer Group at the National Swiss Association for Clinical Cancer Research in Bern Switzerland and Head of Department of Medicine at the Kantonsspital in Winterthur and a supporting coordinating investigator for the study. "The ability for INT230-6 to induce necrosis and activate immune effects before a patient's surgery without increases in toxicity would be a major advance for the treatment of breast cancer and potentially many other cancers." "The majority of breast cancers are immune quiescent, resulting in minimal response to immunotherapies, and larger tumors are less responsive to therapy," said Ursina Zuerer-Haerdi, MD and Lead Physician for the Department of Medical Oncology and Hematology at the Cantonal Hospital in Winterthur, Switzerland and a supporting coordinating investigator on the study. "We have worked with Intensity to design a study for this novel intratumoral agent with the potential to increase the pathological complete response rates of the current best standard of care that would be clinically meaningful, and this trial is of high interest to SAKK's physician network." "INT230-6 is an innovative investigational product that combines cisplatin and vinblastine with a penetration enhancer molecule (SHAO)," said Markus Joerger, Prof. MD-PhD and Coordinating Investigator on the study and principal investigator for the Department of Medical Oncology and Hematology at the Cantonal Hospital St. Gallen. INT230-6 results in local immunogenic cell death when injected into the breast tumor, without systemic chemotoxicity but a high potency to induce systemic immunostimulatory effects. INT230-6 tackles the innate immune pathway that is not addressed by immune checkpoint inhibitors, and it is suggested to complement the systemic neoadjuvant backbone in study patients with early-stage TNBC which consists of chemotherapy and the checkpoint inhibitor pembrolizumab. We believe that the SAKK 66/22 study will provide crucial data to inform a large randomized clinical trial in patients with early-stage TNBC, a disease that is still burdened by substantial rates of fatal relapses following potentially curative treatment." "We are excited to have initiated our Phase 2 study in presurgical triple-negative breast cancer. This study marks the first European patient treated with our drug - a new milestone. Triple-negative is a deadly and aggressive form of breast cancer, and patients having local disease currently undergo a harsh four to six-month regimen whereby a small percentage can die from the SOC before their surgery. Those patients who achieve a pCR have a lower risk of disease recurrence," said Intensity Therapeutics' Founder, Chairman, and CEO, Lewis H. Bender. "We hope that by killing a substantial amount of the tumor upfront and increasing the immune response using INT230-6, we can increase the percentage of patients who achieve pCR and ultimately an improved event-free survival." About INT230-6 INT230-6, Intensity's lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity's proprietary DfuseRx℠ technology platform. The drug comprises two proven, potent anti-cancer agents, cisplatin and vinblastine, and a penetration enhancer molecule (SHAO) that helps disperse potent cytotoxic drugs throughout tumors for diffusion into cancer cells. These agents remain in the tumor, resulting in a favorable safety profile. In addition to local disease control and direct tumor killing, INT230-6 has been shown to release a bolus of neoantigens specific to the malignancy, leading to immune system engagement and systemic anti-tumor effects. Importantly, these effects are mediated without immunosuppression, which often occurs with systemic chemotherapy. About Triple Negative Breast Cancer in the Presurgical Setting Approximately 11-17% of breast cancers test negative for estrogen receptors (ER), progesterone receptors (PR), and excess human epidermal growth factor receptor 2 (HER2) protein, qualifying them as triple negative. TNBC is considered to be more aggressive and has a poorer prognosis than other types of breast cancer, mainly because there are fewer available targeted medicines. Most patients with local TNBC typically receive immune/chemotherapy before surgery. Since the publication of Keynote-522, standard neoadjuvant treatment for TNBC includes systemic chemotherapy (anthracyclines, cyclophosphamide, paclitaxel, carboplatin) and the anti-PD-1 monoclonal antibody pembrolizumab. pCR rates are only 63%, with rates generally lower in the larger-sized T2 to T4 tumors. The toxicity of the Keynote-522 regimen is high, with 80% of patients experiencing grade 3 or higher treatment-related AEs, including treatment-related adverse events that lead to death in 0.5% of patients. About SAKK The Swiss Group for Clinical Cancer Research (SAKK) is a decentralized academic research institute that has been conducting clinical trials of cancer treatments in all major Swiss hospitals since 1965. It federates a large network of research groups with a Competence Center in Bern in charge of coordinating the clinical operations. It also works with selected cooperative groups abroad, particularly on rare forms of cancer. SAKK's aim is to advance existing cancer treatments, investigate the efficacy and tolerability of new treatments (radiotherapy, medicines and surgery), and set new standards in treatment. 22 Swiss hospitals are full members of SAKK. Research activity is funded by federal subsidies provided by the State Secretariat for Education, Research and Innovation (SERI) and financial support from other partner organizations such as the Swiss Cancer League and the Swiss Cancer Research Foundation. Further information can be found at . About Intensity Therapeutics Intensity Therapeutics is a late-stage clinical biotechnology company that applies novel engineered chemistry by enabling its aqueous cytotoxic-containing drug product, INT230-6, to mix and saturate the tumor's dense, high-fat pressurized environment. As a result of the saturation, Intensity's clinical trials have demonstrated the ability of INT230-6 to kill tumors and elicit an adaptive immune response within days of injection, representing a novel approach to cancer cell death that holds the potential to shift the treatment paradigm and turn many deadly cancers into chronic diseases even for cancers that do not respond to immunotherapy. Intensity complete two large clinical studies using INT230-6 that enrolled over 200 patients: a Phase 1/2 dose escalation trial (NCT03058289) and a Phase 2 randomized control clinical trial in breast cancer (the INVINCIBLE-2 study) (NCT04781725). Intensity Therapeutics initiated a Phase 3 trial in soft tissue sarcoma (the INVINCIBLE-3 study) (NCT06263231), testing INT230-6 as second or third-line monotherapy compared to the standard of care with overall survival as an endpoint. The Company is also conducting a Phase 2 study in collaboration with SAKK as part of a Phase 2/3 program evaluating INT230-6 followed by SOC and SOC alone for patients with presurgical triple negative breast cancer. Information on the Phase 2 portion of the program (INVINCIBLE-4 Study) is listed under (NCT06358573). For more information about the Company, including publications, papers and posters about its novel approach to cancer therapeutics, visit . Forward-Looking Statements Certain statements in this press release may constitute "forward-looking statements" within the meaning of the United States Private Securities Litigation Reform Act of 1995, as amended to date. These statements include but are not limited to, statements relating tothe development of the Company's clinical programs. When or if used in this communication, the words "may," "could," "should," "anticipate," "believe," "estimate," "expect," "intend," "plan," "predict" and similar expressions and their variants, as they relate to the Company or its management, may identify forward-looking statements. The forward-looking statements contained in this press release are based on management's current expectations and projections about future events. Nevertheless, actual results or events could differ materially from the plans, intentions, and expectations disclosed in, or implied by, the forward-looking statements. These risks and uncertainties, many of which are beyond our control, include: the initiation, timing, progress and results of future preclinical studies and clinical trials and research and development programs; the need to raise additional funding before the Company can expect to generate any revenues from product sales; plans to develop and commercialize product candidates; the timing or likelihood of regulatory filings and approvals; the ability of the Company's research to generate and advance additional product candidates; the implementation of the Company's business model, strategic plans for the Company's business, product candidates and technology; commercialization, marketing and manufacturing capabilities and strategy; the rate and degree of market acceptance and clinical utility of the Company's system; the Company's competitive position; the Company's intellectual property position; developments and projections relating to the Company's competitors and its industry; the Company's ability to maintain and establish collaborations or obtain additional funding; expectations related to the use of cash and cash equivalents and investments; estimates regarding expenses, future revenue, capital requirements and needs for additional financing; and other risks described in the section entitled "Risk Factors" in the Company's SEC filings, which can be obtained on the SEC website at . Readers are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date on which they are made and reflect management's current estimates, projections, expectations and beliefs. The Company does not plan to update any such forward-looking statements and expressly disclaims any duty to update the information contained in this press release except as required by law. Investor Relations Contact: Justin Kulik [email protected] CORE IR (516) 222-2560 Media Contact: Jules Abraham CORE IR [email protected] SOURCE Intensity Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED