FDPS

Clinical Trials Showcased at Global Gathering FORT MYERS, Fla., April 5, 2024 /PRNewswire/ -- Clinical research conducted at Florida Cancer Specialists & Research Institute, LLC (FCS) will be highlighted at the American Association for Cancer Research 2024 Annual Meeting in San Diego as scientists, clinicians and other health care professionals and stakeholders from all over the world gather to share the latest advances in cancer science and medicine. Continue Reading Over a dozen FCS abstracts will be presented at the 2024 AACR annual meeting. "Finding cancer cures requires diligence and collaboration among the greatest minds in cancer research," noted Lucio N. Gordan, MD, FCS President & Managing Physician. "Through our extensive and growing clinical trials research program, FCS is proud to be part of global efforts that are saving lives and enhancing the quality of life for patients and their families." FCS provides ongoing access to more than 160 clinical trials within 32 FCS clinics and three Drug Development Units (early-phase) across Florida, in Sarasota, Lake Mary and Lake Nona. In recent years, the majority of new cancer drugs approved for use in the U.S. were studied in clinical trials with FCS participation, prior to approval. FCS physician investigators will present findings during oral and poster sessions at the ACCR 2024 Annual Meeting. FCS abstracts at AACR 2024 Annual Meeting: 068, 075, 132, 141, 156, 163, 291, 6552, 7172, 099, 077, 2565 FCS Director of Drug Development Manish Patel, MD, co-author of nine abstracts: Interim results of the ongoing phase 1-2 clinical trial of KVA12123, an engineered IgG1 targeting VISTA, as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors Phase 1 trial evaluating AC699, an orally bioavailable chimeric estrogen receptor degrader, in patients with advanced or metastatic breast cancer Phase I/IIa clinical trial (TranStar101) to evaluate the safety, tolerability and pharmacokinetics of OSEMITAMAB administered as monotherapy or in combination with nivolumab or standard of care in patients with locally advanced or metastatic solid tumors mRNA-4157 (V940) individualized neoantigen therapy (INT) + pembrolizumab (pembro) in advanced unresectable HPV- head & neck carcinoma (HNSCC): Clinical & translational analysis Phase I study evaluating AC676, an innovative BTK chimeric degrader, in patients with relapsed and refractory B-cell malignancies Phase 1 clinical trial of the farnesyl transferase inhibitor KO-2806 alone or as part of combination therapy for advanced solid tumors Phase 1/2, first-in-human study of DS-3939a in patients with advanced solid tumors: A new DXd ADC targeting TA-MUC1 Intratumoral (ITu) delivery of mRNA-2752 encoding human OX40L/IL-23/IL-36γ in combination with durvalumab induces an immunostimulatory effect within the tumor microenvironment (TME) of patients with advanced solid tumors Pharmacokinetic/biomarker (PK/BMx) analysis of the toll-like receptor 7 and 8 (TLR7/8) agonist EIK1001 in phase 1 studies in participants (Pts) with solid tumors FCS Associate Director of Drug Development Judy Wang, MD first author: NGM707 in combination with pembrolizumab in advanced or metastatic solid tumors: Preliminary results from dose escalation FCS Scientific Director of Research and Associate Professor of Medicine, Wake Forest University School of Medicine Lowell Hart, MD, FACP, first author: Vitamin D deficiency and outcomes in prostate cancer patients-A real world database Co-authors include FCS Trial Match Specialist and Medical Oncologist and Hematologist (retired) James Reeves Jr., MD, FCS Nurse Specialist Stacey Garofalo RN and members of the FCS Real-World Evidence Team, IT Director Data Science Derek Hall and Informatics Data Scientist Parth Kothiya. FCS Director of Drug Development, Lake Nona DDU, Cesar Augusto Perez, MD, co-author: Open-label phase 1 study to investigate SGN-CEACAM5C in adults with advanced solid tumors "Our clinical trials research contributes daily to the discovery of ground-breaking new drugs and therapies that are accelerating our understanding of cancer and transforming the standard of care," said FCS Director of Late-Phase Clinical Research Bradley Monk, MD. Dr. Monk is co-author of a study conducted at HonorHealth University of Arizona College of Medicine and Creighton University School of Medicine prior to being named to his leadership position at FCS earlier this year, "Tumor microenvironment (TME) biomarkers of TIGIT and PD-L1 immune checkpoint blockade in cervical cancer: An exploratory biomarker analysis from SKYSCRAPER-04 (SKY04) study." Abstracts will be published in the AACR journal, Cancer Research, following the annual meeting. The American Association for Cancer Research (AACR), the first and largest cancer research organization dedicated to accelerating the conquest of cancer, represents 58,000 members residing in 141 countries. About Florida Cancer Specialists & Research Institute, LLC: (FLCancer.com) Florida Cancer Specialists & Research Institute (FCS) offers patients access to more clinical trials than any private oncology practice in Florida. The majority of new cancer drugs recently approved for use in the U.S. were studied in clinical trials with FCS participation.* Recognized for our research, FCS is a recipient of the national Clinical Trials Participation Award presented by the American Society of Clinical Oncology (ASCO). FCS physicians, trained in prestigious medical schools and research institutes, are consistently ranked nationally as Top Doctors by U.S. News & World Report. Celebrating its 40th year in 2024, FCS has built a national reputation for excellence that is reflected in exceptional and compassionate patient care, driven by innovative clinical research, cutting-edge technologies and advanced treatments, including targeted therapies genomic-based treatment and immunotherapy. Our highest values are embodied by our outstanding team of highly trained and dedicated physicians, clinicians and staff. *Prior to approval SOURCE Florida Cancer Specialists & Research Institute

新生儿期、儿童期、青春期、生育期、围绝经期（更年期）、老年期，女性的一生，要经历多个生理阶段。每个生理阶段，都有独特的生理特征，这些阶段不仅带来身体变化，还可能伴随烦恼与身体病痛，需要及时关注与科学应对。围绝经期是女性由性成熟期过渡至老年期的特殊阶段，中国女性平均于46岁进入围绝经期，持续约10~15年，直到最后一次月经后1年为止。据相关数据推测，到2030年，我国绝经期女性数量将超过2亿，约占全球更年期总人口1/7，其中超过85% 的女性可能会出现不同程度的围绝经期（更年期）症状。如何判断更年期是否来临？根据月经周期天数判断  女性进入更年期的标志为40岁以上女性出现月经周期长度改变，10 次月经周期中有2次或以上发生月经周期改变＞ 7 天（月经周期天数计算：从月经来的第1天开始计算，到下次月经第1天为1个周期）。出现围绝经期常见症状——围绝经期综合征  围绝经期综合征（perimenopausal syndrome，PMS），又称更年期综合征或绝经综合征，是指女性在绝经前后因卵巢分泌的雌激素水平下降所致的一系列躯体及精神心理症状的一类症候群。中医称为“绝经前后诸证”、“经断前后诸证”。更年期症状多数发生于40~60岁的女性。流行病学调查表明，几乎每位女性都有围绝经期症状，仅症状严重程度不同，平均历时3~5年。10%~15%的女性更年期症状表现较为严重，需要药物治疗。50%~75%的女性有明显感觉，还有些女性没有明显症状表现。   更年期综合征主要症状表现为月经失调、潮热、出汗、失眠、情绪异常、骨关节肌肉疼痛、血管舒缩症状、代谢异常及泌尿生殖症状等，严重影响围绝经期妇女的身心健康和生活质量。更年期综合征诊断要点通常情况下，临床中根据以下诊断要点确诊更年期综合征（表1）：          表1 更年期综合征诊断要点注：根据更年期综合征中西医结合诊治指南（2023年版）整理中医药治疗更年期综合征的临床优势多项研究表明，中医药联合西药治疗更年期综合征总有效率优于常规西药治疗，可降低患者Kupperman评分，有效缓解更年期女性潮热盗汗、睡眠障碍、异常子宫出血等症状。此类研究结果也得到专家的一致肯定。治疗更年期综合征的代表性中药——坤心宁颗粒，是2021年天士力获批上市的独家品种，是基于中医经典名方“二仙汤”基础上加减化裁而成。七味合用，共达滋肾养阴，平肝宁心之功。通过开展随机、双盲、安慰剂平行对照、多中心临床试验，获得安全性、有效性证据，被推荐用于女性更年期综合征中医辨证属肾阴阳两虚证的治疗。在Ⅱ期临床试验中，共入组232例，其中试验组118例，安慰剂组114例；Ⅲ期临床试验共入组472例，其中试验组354例，安慰剂组118例。临床试验纳入人群为45~55周岁女性，西医诊断为更年期综合征，中医辨证为肾阴阳两虚证，月经紊乱或停经3个月以上，改良Kupperman评分分值≥16分，FSH＞10U/L者。试验组服用坤心宁颗粒，对照组服用安慰剂，均为一次1袋，一日3次。Ⅱ期临床试验疗程8周，Ⅲ期临床试验疗程12周。Ⅲ期临床试验有效性结果表明，在改良Kupperman总积分等方面，试验组优于安慰剂组。中医证候单项症状潮热汗出、腰背冷痛、乍热乍寒、烦躁易激动、畏寒肢冷、阴道干涩、郁郁寡欢、眩晕、耳鸣、失眠多梦等症状消失率，试验组好于安慰剂组。   作为1.1类创新中药，坤心宁颗粒保留汤剂起效迅速的基础上经过剂型改造，实现药品携带方便，服用量小，提高了患者的顺应性。经过Ⅱ期临床安全性研究、Ⅲ期临床有效性研究及CMC质量控制研究，将有效成分含量控制在精准范围内，既确保产品安全、有效，又确保产品质量稳定、可控。在坤心宁颗粒说明书中，也再次强调了坤心宁应用的注意事项：1、阴虚内热者不宜使用。2、不宜和含“藜芦”的中药方剂或成药同时服用。3、不宜超疗程使用（疗程建议8-12周）。4、服药期间应在医生指导下监测血清激素水平、子宫内膜、乳腺的变化，如出现阴道不规则出血，或阴道出血量多，或乳房肿块、疼痛及子宫内膜息肉，应立即停药并及时去医院就诊。5、有肝肾基础疾病者、肝肾功能异常者慎用。6、尚无与影响激素水平药物联合使用的安全性、有效性数据。7、有妊娠计划者、过敏体质者慎用。更年期骨质疏松的药物干预骨质疏松是更年期综合征中另一常见的症状体征。随着人口老龄化加重，骨质疏松症已严重威胁中老年人尤其是中老年女性的健康，女性骨质疏松症患病率为男性的3倍。研究显示，围绝经及绝经妇女骨质疏松发生率为15.16％。关注围绝经期女性骨质疏松已成为严峻的公共卫生问题。             围绝经期和绝经后妇女骨质疏松症防治的选择应该从多角度考量，包括有效性、风险和成本等。此外，应根据围绝经期和绝经后妇女的特点采取不同阶段的防治措施与方法。围绝经期开始即应采取必要措施维持骨健康，包括培养健康生活方式、摄入充足的钙和维生素D、采用绝经激素治疗（HT）等。另外针对于骨折风险高的女性，包括已经诊断骨质疏松症者和骨量低下（-2.5 ＜ T- 值＜ -1.0）且 FRAX工具计算出未来 10 年髋部骨折概率≥ 3% 或任何主要骨质疏松性骨折发生概率≥ 20% 者，可采用其他抗骨质疏松药物治疗。抗骨质疏松症药物按作用机制可分为骨吸收抑制剂、骨形成促进剂、其他机制类药物及传统中药。双膦酸盐、选择性雌激素受体调节剂、降钙素、甲状旁腺素、地诺单抗等是常见的抗骨质疏松症药物。美国内分泌学会2019年发布的《ENDO 绝经后女性骨质疏松症的药物治疗临床实践指南》推荐，骨折风险高的绝经后女性，初始治疗可选用双膦酸盐类。我国《原发性骨质疏松症诊疗指南（2022）》明确指出：“对于骨折高风险者建议首选口服双膦酸盐”。          米诺膦酸可以有效降低骨折再发风险双膦酸盐有效抑制骨的重吸收，已被证明可有效预防椎体和髋部骨折。这是由于双膦酸盐与骨骼亲和力高，能够特异性结合到骨重建活跃的骨表面，抑制骨吸收、降低骨转换。而米诺膦酸作为目前抗骨吸收能力较强的口服双膦酸盐一直备受关注。作为第三代双膦酸盐的代表性药物，通过抑制破骨细胞内焦磷酸法呢酯(FPP)合成酶活性，抑制破骨细胞的骨吸收，降低骨转换，起到防治骨质疏松的效果。在抑制骨吸收效用方面，米诺膦酸与唑来膦酸相当，是阿仑膦酸的10倍，相比同为口服的阿仑膦酸，米诺膦酸在相似疗效的情况下，使用剂量则明显下降(阿仑膦酸为10mg/天，米诺膦酸为1mg/天)，提高了患者的依从性和减少了双膦酸盐类药物常见的胃肠不良反应，是目前临床上应用较为广泛的抗骨质疏松症药物。需要注意的是，骨质疏松症早期不容易引起围绝经期和绝经后女性关注。因此，妇产科医生应对围绝经期骨质疏松患者进行积极干预，指导患者做好预防、早期筛查与及时防治。    参考资料：[1] 崔满华,李元成,马海鸥.女性一生各阶段的生理变化[J].中国实用妇科与产科杂志,2023,19(1)：23-24[2] WANG M，KARTSONAKI C，GUO Y，et al. Factors related to age at natural menopause in China：results from the China Kadoorie Biobank［J］. Menopause，2021，28（10）：1130-1142. DOI：10.1097/gme.0000000000001829.    [3] 贾钰,周紫彤,曹学华,等.中国 40~65 岁女性围绝经期综合征发生率的 Meta 分析［J］. 中国全科医学,2023. DOI：10.12114/j.issn.1007-9572.2023.0303.[4] Hill K. The demography of menopause［J］. Maturitas,1996,23（2）：113.[5] 《围绝经期综合征（更年期综合征）重点人群治未病干预指南》编写组,中国医学科学院北京协和医院.围绝经期综合征（更年期综合征）重点人群治未病干预指南[J].北京中医药大学学报,2023,46（8）：1048-1062[6] 中国中西医结合学会妇产科专业委员会. 更年期综合征中西医结合诊治指南（2023年版）[J]. 中国实用妇科与产科杂志,2023,39(8):799-808[7] 坤心宁颗粒药品说明书[8] 赵越,谢小芳,韩倩.围绝经期女性骨密度影响因素的研究进展[J].中国妇产科临床杂志,2024,25(1):94-96[9] 中国老年学和老年医学学会骨质疏松分会妇产科专家委员会与围绝经期骨质疏松防控培训部.围绝经期和绝经后妇女骨质疏松防治专家共识[J].中国临床医生杂志,2020,48(8):903-908[10] EASTELL R, ROSEN CJ, BLACK DM, et al. Pharmacological management of osteoporosis in postmenopausal women: an endocrine society* clinical practice guideline[J]. J Clin Endocrinol Metab, 2019, 104(5):1595-1622.[11] 中华医学会骨质疏松和骨矿盐疾病分会．原发性骨质疏松症诊疗指南（2022）［J］．中国全科医学，2023，26（14）：1671-1691.[12] Hagino H, et al. Number and severity of prevalent vertebral fractures and the risk of subsequent vertebral fractures in Japanese women with osteoporosis: results from the minodronate trial. J Bone Miner Metab. 2013 Sep;31(5):544-50.    免责声明：本文仅作最新前沿信息交流之目的，文中所有观点不代表梅斯医学立场，亦不代表梅斯医学支持或反对文中观点。如需获得治疗方案指导，请前往正规医院就诊！

– Company anticipates dosing of KO-2806 in combination with adagrasib in KRASG12C-mutant NSCLC next quarter – – Dose escalation of KO-2806 as a monotherapy continues in parallel – SAN DIEGO, March 06, 2024 (GLOBE NEWSWIRE) -- Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, today announced dosing of the first patient with KO-2806, the Company’s next-generation farnesyl transferase inhibitor (FTI), in combination with the tyrosine kinase inhibitor (TKI) cabozantinib in the clear cell renal cell carcinoma (ccRCC) cohort of the Phase 1 portion of the FIT-001 trial. “Dosing of the first patient in combination in our Phase 1 trial of KO-2806 marks a significant milestone for our next-generation FTI program,” said Stephen Dale, M.D., Chief Medical Officer of Kura Oncology. “This innovative, first-in-human trial builds upon our leadership position in the development of FTIs as well as a growing body of preclinical data demonstrating that combining KO-2806 with certain tyrosine kinase inhibitors, including cabozantinib, has the potential to address mechanisms of innate and adaptive resistance of targeted therapies, while driving tumor regressions and enhancing both duration and depth of antitumor response in preclinical models of ccRCC. With this achievement, we are now one step closer to realizing our vision for broad application of KO-2806 as an ideal combination partner to drive enhanced antitumor activity and address mechanisms of innate and adaptive resistance to targeted therapies.” FIT-001 is a first-in-human, multicenter, open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of KO-2806 when administered as monotherapy and in combination with targeted therapies. Concurrent with the monotherapy dose escalation, Kura is evaluating KO-2806 in dose-escalation combination cohorts with other targeted therapies, beginning with cabozantinib in ccRCC. The Company expects to begin dosing in combination with adagrasib in KRASG12C-mutant non-small cell lung cancer (NSCLC) next quarter. For more information regarding FIT-001, please visit www.clinicaltrials.gov (identifier: NCT06026410). About KO-2806 KO-2806 is a next-generation inhibitor of farnesyl transferase designed to improve upon the potency, pharmacokinetic and physicochemical properties of earlier FTI drug candidates. At the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Kura presented promising preclinical data supporting the rationale for combining KO-2806 with distinct classes of targeted therapies, including tyrosine kinase inhibitors, KRASG12C inhibitors and KRASG12D inhibitors. Additional information about clinical trials for KO-2806 can be found at https://kuraoncology.com/clinical-trials/#farnesyl-transferase-inhibitor. About Kura Oncology Kura Oncology is a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer. The Company’s pipeline consists of small molecule drug candidates that target cancer signaling pathways. Ziftomenib is a once-daily, oral drug candidate targeting the menin-KMT2A protein-protein interaction for the treatment of genetically defined AML patients with high unmet need. Kura is currently enrolling patients in a Phase 2 registration-directed trial of ziftomenib in NPM1-m R/R AML (KOMET-001). The Company is also conducting a series of studies to evaluate ziftomenib in combination with current standards of care, beginning with ven/aza and 7+3 in NPM1-m and KMT2A-r newly diagnosed and R/R AML (KOMET-007) and with the FLT3 inhibitor gilteritinib, FLAG-IDA or LDAC in NPM1-m and KMT2A-r R/R AML (KOMET-008). Tipifarnib, a potent and selective FTI, is currently in a Phase 1/2 trial in combination with alpelisib for patients with PIK3CA-dependent HNSCC (KURRENT-HN). Kura is also evaluating KO-2806, a next-generation FTI, in a Phase 1 dose-escalation trial as a monotherapy and in combination with cabozantinib in ccRCC and with adagrasib in KRASG12C-mutated NSCLC (FIT-001). For additional information, please visit Kura’s website at www.kuraoncology.com and follow us on X and LinkedIn. Forward-Looking Statements This news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, the efficacy, safety and therapeutic potential of KO-2806, potential benefits of combining KO-2806 with appropriate standards of care and expected timing for enrollment in the NSCLC cohort of the FIT-001 trial. Factors that may cause actual results to differ materially include the risk that compounds that appeared promising in early research or clinical trials do not demonstrate safety and/or efficacy in later preclinical studies or clinical trials, the risk that Kura may not obtain approval to market its product candidates, uncertainties associated with performing clinical trials, regulatory filings, applications and other interactions with regulatory bodies, risks associated with reliance on third parties to successfully conduct clinical trials, risks associated with Kura’s cash needs, the risks associated with reliance on outside financing to meet capital requirements, and other risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. You are urged to consider statements that include the words “may,” “will,” “would,” “could,” “should,” “believes,” “estimates,” “projects,” “promise,” “potential,” “expects,” “plans,” “anticipates,” “intends,” “continues,” “designed,” “goal,” or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties the Company faces, please refer to the Company's periodic and other filings with the Securities and Exchange Commission (SEC), including the Company’s Form 10-K for the quarter ended December 31, 2023 filed with the SEC on February 27, 2024, which are available at www.sec.gov. Such forward-looking statements are current only as of the date they are made, and Kura assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Contacts Investors: Pete De Spain Executive Vice President, Investor Relations & Corporate Communications (858) 500-8833 pete@kuraoncology.com Media: Alexandra Weingarten Associate Director, Corporate Communications &Investor Relations(858) 500-8822 alexandra@kuraoncology.com