Capivasertib

400mg BID fed is the dose used in the ongoing Phase 3 ReDiscover-2 trial, which initiated mid-2025 11.1-month median PFS in heavily pre-treated patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer Efficacy in patients with kinase and non-kinase domain mutations is similar, with median PFS of 11.2 and 11.0 months, respectively Safety and tolerability data are consistent with 600mg BID fasted data Zovegalisib has received FDA Breakthrough Therapy designation for the Phase 3 ReDiscover-2 trial population CAMBRIDGE, Mass., March 16, 2026 (GLOBE NEWSWIRE) -- Relay Therapeutics, Inc. (Nasdaq: RLAY), a clinical-stage, small molecule precision medicine company developing potentially life-changing therapies for patients living with cancer and genetic disease, today announced data from the Phase 1/2 ReDiscover trial of zovegalisib (RLY-2608) + fulvestrant at the recommended Phase 3 dose of 400mg twice daily (BID) taken with food (fed) in patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer. The data are being presented at the European Society for Medical Oncology (ESMO) Targeted Anticancer Therapies (TAT) Congress 2026 in Paris, France. “As supported by the data presented, the 400mg BID fed regimen maintains robust efficacy with a safety pro with mutant-selective PI3Kα inhibition,” said Don Bergstrom, M.D., Ph.D., President of R&D at Relay Therapeutics. “These results further support our decision to advance this regimen into the ongoing Phase 3 ReDiscover-2 trial and reinforce our confidence in selectively targeting PI3Kα mutations as a potentially differentiated approach for CDK4/6-experienced patients.” Phase 1/2 ReDiscover Trial – Zovegalisib 400mg Fed Cohort Data Consistent with 600mg Fasted Data Zovegalisib is currently being evaluated in ReDiscover, an ongoing first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of zovegalisib in combination with fulvestrant and in combination with fulvestrant and CDK inhibitors in patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer. As of the January 13, 2026 data cut-off date, 60 patients had received the 400mg BID fed regimen. The efficacy population consisted of 57 patients who did not have a PTEN or AKT co-mutation, consistent with the planned pivotal population. All patients had previously received a CDK4/6 inhibitor and at least one prior endocrine therapy in the advanced setting. Pharmacokinetics of Both Doses are Similar Pharmacokinetic analyses demonstrate that the 400mg BID fed regimen achieves exposures comparable to the previously evaluated 600mg BID fasted dose, with mean concentrations approaching IC90 in majority of patients and nearly all patients maintaining exposure above the IC80 throughout the dosing interval. Efficacy Consistent with 600mg BID Fasted As of the January 13, 2026 data cut-off date, among the 57 efficacy-evaluable patients at the 400mg BID fed dose, which is the recommended Phase 3 dose (RP3D): Median follow-up was 12.0 months Median progression-free survival (PFS) was 11.1 months (95% CI: 7.3–13.0) Median PFS was 11.2 months in patients with kinase mutations (n=33) and 11.0 months in patients with non-kinase mutations (n=24) Among 35 patients with measurable disease, confirmed objective response rate (ORR) was 43% (15/35) and in second line only patients the ORR was 52% (11/21) Maintained Favorable and Differentiated Tolerability Profile Zovegalisib + fulvestrant at the 400mg BID fed dose was generally well tolerated in the 60 treated patients as of the January 13, 2026 data cut-off. The overall tolerability pro primarily of low-grade, manageable and reversible treatment-related adverse events (TRAEs). Safety pro with previously disclosed 600mg BID fasted data Majority of hyperglycemia events were Grade 1; no Grade 4-5 hyperglycemia observed In the limited cases of Grade 2/3 hyperglycemia, the vast majority occurred in patients that were pre-diabetic at baseline Only four patients discontinued due to TRAEs The data presentation from the ESMO TAT Congress 2026 is available on the Relay Therapeutics website in the “Publications/Presentations” section through the following link: . ReDiscover-2 – Ongoing Phase 3 Trial The Phase 3 ReDiscover-2 trial (NCT06982521) is evaluating zovegalisib 400mg BID administered in combination with fulvestrant versus capivasertib + fulvestrant in patients with PI3Kα-mutated, HR+/HER2- advanced breast cancer who have progressed on prior CDK4/6 inhibitor therapy. The study initiated in mid-2025 and is enrolling globally. Zovegalisib + fulvestrant has received FDA Breakthrough Therapy designation for the Phase 3 ReDiscover-2 trial population. About Zovegalisib Zovegalisib is the lead program in Relay Therapeutics’ efforts to discover and develop mutant selective inhibitors of PI3Kα, the most frequently mutated kinase in all cancers and all vascular anomalies. Zovegalisib has the potential, if approved, to address a significant portion of the approximately 140,000 patients with HR+/HER2- breast cancer with a PI3Kα mutation and the estimated 170,000 patients with vascular anomalies driven by a PI3Kα mutation per year in the United States, one of the largest patient populations for a precision medicine. Traditionally, the development of PI3Kα inhibitors has focused on the active, or orthosteric, site. The therapeutic index of orthosteric inhibitors is limited by the lack of clinically meaningful selectivity for mutant versus wild-type (WT) PI3Kα and off-isoform activity. Toxicity related to inhibition of WT PI3Kα and other PI3K isoforms results in sub-optimal inhibition of mutant PI3Kα with reductions in dose intensity and frequent discontinuation. The Dynamo® platform enabled the discovery of zovegalisib, the first known allosteric, pan-mutant, and isoform-selective PI3Kα inhibitor, designed to overcome these limitations. Relay Therapeutics solved the full-length cryo-EM structure of PI3Kα, performed computational long time-scale molecular dynamic simulations to elucidate conformational differences between WT and mutant PI3Kα, and leveraged these insights to support the design of zovegalisib. Zovegalisib is currently being evaluated in multiple metastatic breast cancer studies and a first-in-human study designed to treat patients with PIK3CA (PI3Kα) mutation driven vascular anomalies. For more information on zovegalisib, please visit here . About Relay Therapeutics Relay Therapeutics (Nasdaq: RLAY) is a clinical-stage, small molecule precision medicine company developing potentially life-changing therapies for patients living with cancer and genetic disease. Relay's Dynamo® platform integrates an array of leading-edge computational and experimental approaches designed to drug protein targets that have previously been intractable or inadequately addressed. The company’s lead clinical asset, zovegalisib, is the first pan-mutant selective PI3Kα inhibitor to enter clinical development and is currently in a Phase 3 clinical trial (ReDiscover-2) in HR+/HER2- metastatic breast cancer. Zovegalisib is also being investigated in a group of genetic disease indications called PI3Kα-driven vascular anomalies. Relay's pipeline also includes programs for NRAS-driven solid tumors and Fabry disease. For more information, please visit or follow us on LinkedIn . Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding Relay Therapeutics’ strategy, business plans and focus; the progress and timing of the clinical development of the programs across Relay Therapeutics’ portfolio; the timing of clinical data readouts for zovegalisib; the expected therapeutic benefits and potential efficacy and tolerability of zovegalisib, both as a monotherapy and in combination with other agents, and its other programs; the clinical data for zovegalisib; the interactions with regulatory authorities and any related approvals; and the potential commercialization and market opportunity for zovegalisib. The words “may,” “might,” “will,” “could,” “would,” “should,” “plan,” “anticipate,” “intend,” “believe,” “expect,” “estimate,” “seek,” “predict,” “future,” “project,” “potential,” “continue,” “target” and similar words or expressions, or the negative thereof, are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: the impact of global economic uncertainty, geopolitical instability and conflicts, or public health epidemics or outbreaks of an infectious disease on countries or regions in which Relay Therapeutics has operations or does business, as well as on the timing and anticipated results of its clinical trials, strategy, future operations and profitability; significant political, trade or regulatory developments, such as tariffs, beyond Relay Therapeutics’ control; the delay or pause of any current or planned clinical trials or the development of Relay Therapeutics’ drug candidates; the risk that the preliminary or interim results of its preclinical or clinical trials may not be predictive of future or final results in connection with future clinical trials of its product candidates and that interim and early clinical data may change as more patient data become available and are subject to audit and verification procedures; Relay Therapeutics’ ability to successfully demonstrate the safety and efficacy of its drug candidates; the timing and outcome of its planned interactions with regulatory authorities; and obtaining, maintaining and protecting its intellectual property. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in Relay Therapeutics’ most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q, as well as any subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Relay Therapeutics' views only as of today and should not be relied upon as representing its views as of any subsequent date. Relay Therapeutics explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Contact: Pete Rahmer prahmer@relaytx.com Media: Dan Budwick 1AB 973-271-6085 dan@1abmedia.com

01 显著延长PFS与OS！正大天晴TQB3454胆道癌III期期中分析达优效 3月12日，中国生物制药发布公告，其附属公司正大天晴自主研发的国家1类创新药TQB3454（IDH1抑制剂）治疗伴IDH1突变晚期胆道癌III期临床研究已完成方案预设的期中分析，独立数据监查委员会（IDMC）判定主要研究终点无进展生存期（PFS）、总生存期（OS）均达到方案预设的优效界值。 公告显示，这是全球第2个、国内第1个IDH1抑制剂在胆道癌取得成功的III临床研究。 TQB3454-III-01研究 (NCT05987358) 是一项随机、双盲、安慰剂对照、多中心的Ⅲ期临床研究，旨在评估TQB3454片在既往经含吉西他滨和氟尿嘧啶类为基础联合方案治疗失败的伴IDH1突变的晚期胆道癌中的有效性和安全性。 期中分析结果显示，相比对照组，TQB3454可显著降低晚期胆道癌患者的疾病进展或死亡风险，显著延长患者的PFS和OS。其安全性数据与已知风险一致，未发现新的安全性信号。正大天晴计划于今年开展的国际权威学术大会公布详细研究数据。 TQB3454已于2023年4月被CDE纳入突破性治疗药物程序。正大天晴已经与CDE就该适应症的上市申请进行沟通，并获得CDE书面同意，将于近期递交上市申请。 02 全球首款靶向RAS G12V突变TCR×CD3双抗获批美国临床 3月12日，上海灵识质源生物技术有限公司（Shanghai Essight Biotechnology Co.,Ltd）ES502注射液获得FDA批准I期临床试验，用于治疗具有RAS G12V（KRAS/NRAS/HRAS）突变的晚期实体瘤患者。 ES502是灵识质源（Essight Bio）自主研发的新一代TCRxCD3双抗（T-Cell Engager），可特异性和高亲和力结合pHLA复合体（RAS G12V与目标HLA形成），其对pHLA的亲和力是对CD3亲和力的100倍以上。 在临床前研究中，ES502对多种RAS G12V阳性肿瘤均表现出显著的抗肿瘤活性，并呈现出良好的组织器官安全性及药代动力学特征。ES502是全球首个进入临床阶段的靶向RAS G12V的TCRxCD3双抗，可覆盖全球30-70%具有RAS G12V突变的患者。 RAS G12V突变约占人类实体瘤4-5%，根据WHO统计每年美国和中国新发肿瘤患者携带RAS G12V突变患者数量分别达到10万和20万人，目前尚无有效治疗手段。随着目前RAS抑制剂（例如分子胶）临床进行，第一代耐药人群已经出现（Sumit Kar, AACR, 2025）信号通路选择压力导致RAS Amplification和MAPK/PI3K多重突变导致耐药。 ES502提供一种全新的抗肿瘤作用机制，介导T细胞杀伤RAS G12V阳性肿瘤，相比小分子RAS抑制剂具有更好的特异性和更宽的治疗窗口，其独特杀伤机制有利于克服肿瘤耐药。 ES502获批美国临床，是TCRxCD3双抗在肿瘤治疗领域的一大突破。同时，作为一款中国本土“First-in class”药物，其本身也代表了中国创新的高度。 03 齐鲁制药：5T4 ADC启动一期临床 3月12日，齐鲁制药在Clinicaltrials.gov网站上注册了的QLS5212治疗晚期实体瘤的一期临床试验。 该一期临床试验计划入组100例晚期实体瘤患者，预计2027年11月初步完成。 根据临床注册信息，QLS5212为一款5T4（TPBG）ADC新药。 5T4在宫颈癌、结直肠癌、胃癌、卵巢癌、肾癌等瘤种常见高表达。国内方面，信立泰的5T4双表位ADC新药JK06、爱科瑞思的5T4 ADC新药ACR246、齐鲁制药的5T4 ADC新药QLS5212等陆续推进到临床阶段。 04 华东医药ADC新药三项适应症获FDA孤儿药资格 3月11日，华东医药宣布，其全资子公司中美华东自主研发的抗体偶联药物（ADC）创新药注射用HDM2017的胆道癌、胃癌和胰腺癌三项适应症获得美国FDA孤儿药资格（ODD）。注射用HDM2017是由中美华东研发的1类生物生物新药，是一款靶向钙黏蛋白17（Cadherin17，LI-cadherin）的新型ADC。 CDH17是钙依赖性蛋白质（Cadherins）超家族的非经典成员，是一种钙依赖性细胞粘附跨膜糖蛋白，负责维持组织完整性和形态发生，在正常组织中局限于肠上皮基底外侧膜表达，而在结直肠癌、胃癌及胰腺癌等消化道恶性肿瘤中呈现显著过表达，其异常高表达与肿瘤侵袭转移及不良预后密切相关，是靶向药物的理想靶点。 HDM2017通过抗体的靶向作用特异性识别CDH17阳性表达的肿瘤表面抗原，利用抗原介导的内化作用使ADC进入肿瘤细胞内部，连接子断裂，向胞内释放毒素载荷，发挥抗肿瘤作用；同时HDM2017的旁观者效应进一步发挥肿瘤杀伤效果。临床前研究结果显示，HDM2017具有良好的成药性、安全性和有效性；HDM2017在靶点阳性的结直肠癌、胰腺癌、胃癌等药效模型中显示出强大的抗肿瘤效果；在动物试验中耐受性良好。 注射用HDM2017中国和美国的临床试验申请于2025年9月分别获得中国NMPA和美国FDA批准，适应症为晚期恶性实体瘤。 05 阿斯利康两款肿瘤药将接受FDA专家小组审判 近日，FDA官网宣布将在2026年4月30日召开肿瘤药物咨询委员会（ODAC）会议，就阿斯利康递交的两项上市申请展开讨论：①口服SERD药物Camizestrant联合CDK4/6抑制剂一线治疗存在ESR1突变的局部晚期或转移性HR+/HER2-乳腺癌②AKT抑制剂Capivasertib联合阿比特龙治疗存在PTEN缺陷的转移性激素敏感性前列腺癌（mHSPC）。 Camizestrant是阿斯利康自主研发的下一代口服选择性雌激素受体降解剂（SERD），已在美国、欧洲和日本申报上市。 2025年2月，Camizestrant联合CDK4/6抑制剂对比芳香化酶抑制剂（阿那曲唑或来曲唑）联合CDK4/6抑制剂一线治疗乳腺癌的III期SERENA-6研究在中期分析时达到了无进展生存期（PFS）主要终点。 该研究是首个采用循环肿瘤DNA（ctDNA）指导方法检测内分泌耐药性的全球双盲注册III期试验，纳入了经ctDNA检测在一线内分泌治疗中出现ESR1突变且未出现疾病进展的局部晚期或转移性HR+/HER2-乳腺癌患者。 阿斯利康在ASCO 2025大会上展示的数据显示，截至2024年11月28日，中位随访12.6个月时，Camizestrant联合CDK4/6抑制剂组患者的PFS较对照组显著延长（16.0 vs 9.2个月，HR=0.44，P<0.00001）；PFS达到12个月的患者比例分别为60.7%和33.4%，PFS达到24个月的患者比例分别为29.7%和5.4%。 阿斯利康在SABCS 2025大会上展示的数据显示，截至2025年6月30日，中位随访18.7个月时，Camizestrant联合CDK4/6抑制剂组患者的PFS较对照组显著延长（16.6 vs 9.2个月，HR=0.46，P<0.00001）；PFS达到24个月的患者比例分别为32.2%和14.3%；PFS2分别为25.7个月和19.4个月（HR=0.56，名义P=0.00153），PFS2达到24个月的患者比例分别为50.9%和34.8%。 Capivasertib是阿斯利康自主研发的一款AKT1/2/3高效选择性抑制剂。AKT信号通路的激活，包括PIK3CA、AKT1和PTEN的改变，可出现在许多HR+/HER2-的晚期乳腺癌患者中，但也可能出现在没有这些基因改变的患者中。AKT信号通路与内分泌治疗耐药的发生有关。 2023年11月，Capivasertib首次在美国获批上市，用于联合氟维司群治疗转移性阶段至少接受过一种内分泌治疗后疾病进展，或在辅助治疗期间或完成辅助治疗后12个月内复发的HR+/HER2-且伴有一种或多种PIK3CA/AKT1/PTEN改变的局部晚期或转移性乳腺癌成人患者。 2024年11月，Capivasertib联合阿比特龙对比安慰剂联合阿比特龙治疗存在PTEN缺陷的mHSPC的III期CAPItello-281研究达到了影像学无进展生存期（rPFS）主要终点。 阿斯利康在ESMO 2025大会上展示的数据显示，截至2024年10月7日，Capivasertib联合阿比特龙组患者的rPFS较对照组有所延长（33.2 vs 25.7个月，HR=0.81，P=0.034）。 06 金赛药业1类新药获FDA孤儿药资格，治疗胰腺癌 3月11日，金赛药业宣布，其自主研发的GenSci128片已获得美国FDA授予的孤儿药资格（ODD），用于胰腺癌的治疗。 胰腺癌作为消化道系统恶性程度最高的肿瘤之一，具有高度侵袭性和极差的预后，长期以来一直是临床治疗的巨大挑战。 TP53是人类癌症中最常发生突变的基因。TP53基因编码的p53蛋白作为转录因子，具有抑制肿瘤的功能。TP53基因突变导致p53蛋白失活，是肿瘤发生的关键步骤。其中，TP53 Y220C突变约占TP53突变的1.8%。全球范围内尚无靶向TP53 Y220C突变的治疗药物获批，临床上仍存在巨大的未被满足需求。 GenSci128片是一种针对TP53 Y220C突变的选择性重激活剂，在中国属于治疗用化药1类新药，旨在选择性地与TP53 Y220C突变蛋白的口袋结合，从而恢复TP53 Y220C突变蛋白的正常构象，增加稳定性，恢复转录和抑制肿瘤的功能。临床前数据表明GenSci128片具有较好的疗效和安全性。 GenSci128片在美国新药注册类别"505b1"，拟用于治疗携带TP53 Y220C突变的局部晚期或转移性实体瘤，涵盖胰腺癌、卵巢癌、乳腺癌、结直肠癌等。其新药临床试验申请已获得FDA批准。此前，GenSci128片也已在中国获批开展用于携带TP53 Y220C突变的局部晚期或转移性实体瘤的临床试验。 在肿瘤领域，金赛药业正形成多元化的管线矩阵：除GenSci128外，EGFR/HER2的双靶点ADC药物GenSci139、针对FRα的双表位ADC药物GenSci140以及新型突变选择性PI3Kα抑制剂GenSci145等均已进入临床阶段。 第707期 END 【版权说明】 本文由《聚焦CA》整理发布，内容来源于insight数据库、医药观澜等，侵删。资料为仅用于学术会议或活动的专业资料，旨在促进医药信息的沟通和交流，仅供医疗卫生专业人士参考。转载请保留以上完整出处，文章版权归原作者所有。如有版权问题或商讨其他合作请联系邮箱：focusca@yingmingcg.com。 公众号又又又改版了！ 不互动以后就看不到我了哟~ 快来点赞分享推荐三连一波！