Albumin-Bound Paclitaxel

编者按：局部晚期头颈部鳞状细胞癌（LA-HNSCC）的新辅助治疗，既要争取肿瘤退缩和手术机会，也要尽量减少对器官功能及生活质量的影响。2026年欧洲肿瘤内科学会（ESMO）年会上，一项艾帕洛利托沃瑞利单抗（以下简称“艾托组合抗体”）联合白蛋白紫杉醇、奈达铂的新辅助探索研究公布初步结果。截至2026年4月，研究纳入12例患者；队列中下咽癌占比较高，PD-L1 CPS＜20患者占多数，研究报告了较高的客观缓解率和病理缓解率。该研究为单臂、小样本探索，仍需对照研究和长期随访验证。《肿瘤瞭望》就研究设计、病理缓解的解读、适宜人群及功能结局采访徐伟教授。 局部晚期头颈鳞癌新辅助治疗成绩亮眼，潜力初显 《肿瘤瞭望》：在PD-L1低表达患者占比较高、下咽癌患者较多的局部晚期头颈鳞癌队列中，艾托组合抗体联合化疗取得了较高的客观缓解率和病理缓解率。放在当前新辅助治疗探索中，您如何解读这组结果？ 徐伟 教授 山东省第二人民医院 临床评估新辅助方案，首先要看两个问题：术前能否让肿瘤充分退缩，患者能否按计划接受手术。对局部晚期头颈鳞癌来说，治疗目标不只是影像上的缩小，还包括争取切除机会、降低手术难度，并为保留器官功能创造条件。术前治疗还必须避免拖延手术或增加围手术期风险。 研究纳入既往未接受系统治疗的局部晚期患者，分期为AJCC第8版T2-4aN0-3M0。患者接受艾托组合抗体（5 mg/kg，每3周一次）联合白蛋白紫杉醇（260 mg/m²）和奈达铂（80 mg/m²），共两个周期；治疗结束后3至6周安排手术。这样的设计把新辅助疗程控制在较短时间内，随后进入手术评估。 截至2026年4月，共有12例患者入组，其中下咽癌占58.3%，PD-L1 CPS＜20者占66.7%。研究报告的ORR为100%（12/12），其中CR为50%（6/12）；9例接受手术的患者中，pCR率为55.6%（5/9），MPR率为100%（9/9）。在这组初治、局部晚期且下咽癌占比较高的患者中，研究观察到较高的术前缓解率。 本研究仅纳入12例患者，且为单臂探索性研究，现阶段尚不能据此判断艾托组合抗体联合化疗优于其他新辅助方案，也不宜与不同研究的缓解率直接比较。后续仍需更大样本研究验证疗效，并观察其对手术实施和长期疾病控制的影响 从病理缓解到生存获益，追求卓越步履不停 《肿瘤瞭望》：本研究的pCR和MPR结果较高。临床上应如何理解病理缓解与患者长期获益之间的关系？后续随访应重点观察哪些终点？ 徐伟 教授 山东省第二人民医院 pCR和MPR反映新辅助治疗后肿瘤残留的变化，是重要的早期病理评价指标。病理缓解较深，可能意味着肿瘤负荷下降，并可能有利于局部控制和后续治疗；但这两个指标不能替代生存结局，也不能单独证明患者会获得更长生存。头颈鳞癌预后还受原发部位、T/N分期、切缘状态、淋巴结残留、术后治疗、复发转移及HPV状态等因素影响。 本研究9例手术患者的MPR率为100%、pCR率为55.6%，目前只能说明观察到病理缓解信号，不能据此认定长期临床获益。能否改善无事件生存、无进展生存或总生存，这些仍需后续随访观察。 后续观察首先要看手术能否按计划实施，包括R0切除率、切除范围、围手术期并发症及术后恢复情况；同时还要随访局部区域复发、远处转移以及EFS、PFS和OS。对于头颈部肿瘤，喉功能、吞咽、营养状态、康复进程和患者报告的生活质量同样重要。治疗目标不只是控制肿瘤，还要尽可能保留患者进食、吞咽和交流的能力，这些都是患者能够直接感受到的治疗结局。 《肿瘤瞭望》：目前局部晚期头颈鳞癌新辅助治疗尚无统一的最优方案。结合这项研究的疗效与安全性结果，哪些患者适合进入后续研究？走向临床应用前还需要补齐哪些证据？ 徐伟 教授 山东省第二人民医院 按本研究的入组条件，后续研究可优先纳入体能状态较好、初治、局部晚期且经多学科评估具有明确手术目标的患者。原研究纳入年龄18至75岁、ECOG评分0至1、T2-4aN0-3M0患者。是否适合新辅助治疗，不能只看分期；头颈外科、肿瘤内科和放疗科等团队还要共同评估患者能否耐受方案、手术时机是否可控，以及治疗后是否仍有合理的根治性局部治疗路径。 本研究中CPS＜20患者占66.7%，说明队列中PD-L1低表达患者较多，但现有样本量不足以证明这一亚组获益更大。艾托组合抗体同时作用于PD-1和CTLA-4通路，这为研究提供了机制假设；要明确哪些患者获益，还需在更大样本中结合CPS、原发部位、TNM分期、HPV状态及肿瘤免疫特征进行分析。 安全性需要结合术前治疗场景评估。12例患者中，治疗相关不良事件发生率为83.3%，≥3级治疗相关不良事件为25.0%；免疫相关不良事件发生率为25.0%，≥3级为8.3%，以皮疹为主；骨髓抑制发生率为58.3%，≥3级为25.0%，未报告治疗相关死亡。目前研究中观察到的毒性事件可以管理，但小样本不足以完整界定风险。后续研究还应报告毒性发生时间、处理方式、手术是否延期、围手术期并发症及术后辅助治疗衔接情况。 兼顾控瘤与保功能，探索新辅助治疗逻辑闭环 《肿瘤瞭望》：头颈部肿瘤治疗需要兼顾肿瘤控制与器官功能。未来新辅助研究应如何把患者的生活质量和治疗负担纳入评价？ 徐伟 教授 山东省第二人民医院 头颈部肿瘤治疗会直接影响吞咽、发声、营养和外观，因此评价新辅助治疗不能只看肿瘤缩小多少。缓解率提高很重要；如果治疗毒性明显、手术并发症增加，或患者长期吞咽和发声功能受损，整体获益就需要重新衡量。 未来研究除ORR、pCR和生存终点外，还应预先纳入器官功能、吞咽与喉功能、营养状态、患者报告生活质量、康复结局及治疗相关不良反应，并使用稳定、可比较的评估工具随访。治疗前应记录患者原有的吞咽、发声和营养状况，后续才能判断变化是否与治疗有关。 这需要外科团队评估切除和功能保留，肿瘤内科及放疗科负责系统治疗和局部治疗衔接，营养与康复团队参与治疗期间和术后管理。评价新辅助治疗，既要看肿瘤是否退缩，也要看患者能否获得可靠的疾病控制，以及治疗后能否尽可能保留日常功能。 初探给出亮眼信号，头颈鳞癌新辅助治疗前路可期 这项研究将艾托组合抗体联合化疗用于局部晚期头颈鳞癌的新辅助治疗，在探索术前肿瘤退缩的同时，也提出了一个重要的临床问题：如何让患者顺利接受后续手术，并尽可能保留吞咽、发声等功能。研究观察到病理缓解信号，为这一治疗路径的后续研究提供了依据。现阶段结果来自小样本单臂研究，尚不能证明该方案优于其他治疗，也不能仅凭病理缓解推断长期生存或器官功能获益。 未来仍需通过更大样本、适当的对照研究和长期随访，明确疗效与安全性，并观察术前治疗对手术时机、切除情况和围手术期恢复的影响。除局部复发、远处转移及生存结局外，吞咽和喉功能、营养状态与患者报告的生活质量也应纳入评价。随着PD-L1表达、原发部位、HPV状态等因素的研究积累，临床有望更清楚地了解哪些患者适合探索这一方案，为个体化治疗提供依据。 徐伟 教授 山东省第二人民医院 山东省耳鼻喉医院党委书记 二级教授，博士研究生导师 第六届国之名医卓越建树奖，国务院特贴专家 中华医学会耳鼻咽喉头颈外科分会头颈学组副组长 中华耳鼻咽喉头颈外科杂志编委 山东省医师协会副会长，耳鼻咽喉科分会主任委员，山东省耳鼻咽喉专业质量控中心主任 （来源：《肿瘤瞭望》编辑部） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

Topline results from the Phase 2 PIK-201 trial in endometrial cancer expected by year-end FDA granted Fast Track designation to PIKTOR plus paclitaxel in biomarker-selected advanced endometrial cancer Presented preclinical data on PIKTOR in HR+/HER2- breast cancer models at ESMO 2026 AUSTIN, Texas--(BUSINESS WIRE)--Faeth Therapeutics (Nasdaq: FTH), a clinical-stage oncology company developing multi-node therapies for cancer patients, including its lead program PIKTOR, today announced financial results for the quarter ended September 30, 2026, and highlighted recent corporate accomplishments and 2026 milestones. “Since our last quarterly update, we presented PK/PD analysis that informed the PIKTOR dose in our Phase 2 PIK-201 trial and received Fast Track designation for PIKTOR plus paclitaxel in biomarker-selected advanced endometrial cancer,” said Anand Parikh, Chief Executive Officer. “The PAM pathway is dysregulated in up to 50% of solid tumors, and feedback reactivation and resistance mutations may limit single-node inhibitors. We designed PIKTOR, an all-oral, multi-node inhibitor, to address those limitations, and we believe it has the potential to give patients a differentiated treatment option. We look forward to reading out topline data from our Phase 2 PIK-201 trial in endometrial cancer by year-end, and to reporting initial safety and efficacy data from our PIK-101 trial in HR+/HER2- breast cancer in 2027.” Recent Corporate Updates: Presented preclinical data on PIKTOR in HR+/HER2- breast cancer models at the European Society for Medical Oncology (ESMO) Congress 2026 (Abstract 431P). PIKTOR was tested as monotherapy and in combination with SERDs and CDK inhibitors. In these preclinical models, PIKTOR suppressed key signaling nodes in the PAM pathway, including AKT, at rates comparable to or exceeding those observed with tested single-node inhibitors Presented PK/PD analysis at the 2026 Summit for Novel Therapeutics in Oncology & Precision Medicine in Cancer (STOP Cancer) that informed selection of 3 mg sapanisertib and 200 mg serabelisib three days a week as the recommended Phase 2 dose for PIKTOR in the PIK-201 trial FDA granted Fast Track designation to PIKTOR in combination with paclitaxel for the treatment of patients with advanced or recurrent endometrial cancer whose tumors harbor a PI3K/AKT/mTOR (PAM) pathway alteration and who have previously been treated with platinum-based chemotherapy and an immune checkpoint inhibitor Hosted a virtual key opinion leader event on multi-nodal inhibition for the treatment of endometrial cancer featuring Marcus Goncalves, M.D., Ph.D., of NYU Langone Health and a scientific co-founder of Faeth. A replay is available here Appointed Deepak Tiwari as Senior Vice President, Technical Operations, and Matt Biegler as Senior Vice President, Investor Relations, and added Karen Vousden, Ph.D., and Adam Schayowitz, Ph.D., MBA, to the Board of Directors Third Quarter 2026 Financial Results Cash, Cash Equivalents and Marketable Securities: Cash, cash equivalents and marketable securities were $174.8 million as of September 30, 2026, as compared to $21.2 million as of December 31, 2025. Research and Development Expenses (R&D): R&D expenses for the quarter ended September 30, 2026 were $11.7 million, compared to $2.5 million for the quarter ended September 30, 2025. The increase in R&D expenses was primarily driven by development costs for PIKTOR and other Faeth programs, including clinical trial, chemistry, manufacturing and controls (CMC) and preclinical expenses, together with higher personnel costs, partially offset by lower clinical trial costs for legacy Sensei programs. General and Administrative Expenses (G&A): G&A expenses for the quarter ended September 30, 2026, were $10.4 million, compared to $2.3 million for the quarter ended September 30, 2025. The increase in G&A expenses was primarily attributable to higher personnel costs and increased external administrative fees, primarily legal fees. Net Loss: Net loss was $20.4 million, or $0.79 per basic and diluted share, for the quarter ended September 30, 2026, compared with a net loss of $4.6 million, or $3.62 per basic and diluted share, for the quarter ended September 30, 2025. Weighted-average common shares outstanding, basic and diluted, were 25,840,555 for the quarter ended September 30, 2026, compared with 1,261,290 for the quarter ended September 30, 2025. Condensed Statements of Operations (Unaudited, in thousands except share and per share data) For the Three Months Ended September 30, 2026 2025 Operating expenses: Research and development $ 11,736 $ 2,536 General and administrative 10,350 2,315 Total operating expenses 22,086 4,851 Loss from operations (22,086 ) (4,851 ) Total other income 1,688 282 Net loss (20,398 ) (4,569 ) Net loss per share, basic and diluted $ (0.79 ) $ (3.62 ) Weighted-average common shares outstanding, basic and diluted 25,840,555 1,261,290 Selected Condensed Balance Sheet Data (Unaudited, in thousands) September 30, 2026 December 31, 2025 Cash and cash equivalents $ 14,180 $ 8,668 Marketable securities 160,615 12,516 Total assets 178,949 22,902 Total liabilities 11,085 4,310 Series B redeemable convertible preferred stock 6,767 — Total stockholders’ equity 161,097 18,592 About PIKTOR PIKTOR is an investigational, proprietary, all-oral combination of serabelisib, a selective PI3K-alpha inhibitor, and sapanisertib, an mTORC1/mTORC2 inhibitor, designed to inhibit multiple nodes of the PI3K/AKT/mTOR pathway. This multi-node approach is designed to address the signaling feedback reactivation and treatment-emergent resistance mutations that may limit the efficacy of single-node PI3K/AKT/mTOR pathway inhibitors. According to published literature, the PAM pathway is dysregulated in up to 50% of all solid tumors, making it one of the most prevalent therapeutic targets in oncology. PIKTOR is being evaluated in a Phase 2 trial in second-line advanced endometrial cancer (Study FTH-PIK-201), with topline data anticipated by year-end 2026. PIKTOR is also being evaluated in a Phase 1b/2 trial in HR+/HER2- advanced breast cancer (Study FTH-PIK-101), in which the first patient was dosed in April 2026 and interim data is anticipated in 2027. About Faeth Therapeutics Faeth Therapeutics, Inc. (Nasdaq: FTH) is a clinical-stage biotechnology company focused on improving outcomes for cancer patients through multi-node inhibition of critical oncogenic pathways. The Company’s lead program is PIKTOR, an investigational all-oral combination of serabelisib and sapanisertib in development for endometrial and breast cancer. Faeth was co-founded in 2019 by Anand Parikh and Oliver Maddocks, Ph.D., together with scientific founders Lewis Cantley, Ph.D., the discoverer of the PI3K pathway; Siddhartha Mukherjee, M.D., D.Phil.; Karen Vousden, Ph.D.; Scott Lowe, Ph.D.; and Greg Hannon, Ph.D. The Company intends to use its website as a means of disclosing material non-public information and for complying with its disclosure obligations under Regulation FD. For more information, please visit and follow the Company on LinkedIn . Cautionary Note Regarding Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the federal securities laws, including the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements that are not historical facts and may be identified by words such as “anticipate,” “believe,” “expect,” “intend,” “plan,” “may,” “will,” “would,” “could,” “should,” “estimate,” “potential,” “target,” “on track” and similar expressions, although not all forward-looking statements contain these words. These statements include, but are not limited to, statements regarding: the Company’s interpretation of preclinical, pharmacokinetic and pharmacodynamic data and the conclusions the Company draws from that data, including with respect to dose and schedule selection for PIKTOR and comparisons of PIKTOR’s preclinical pro that of other tested inhibitors; the anticipated benefits of Fast Track Designation; the Company’s expectations regarding its pipeline and development plans, including the Phase 2 trial of PIKTOR in advanced endometrial cancer and the anticipated timing of topline data, and the Phase 1b/2 trial of PIKTOR in HR+/HER2- advanced breast cancer and the anticipated timing of interim data; the potential therapeutic benefits, tolerability pro differentiation of PIKTOR; and the Company’s expectations regarding its cash runway. Forward-looking statements are based on management’s current expectations and assumptions and are subject to a number of risks and uncertainties, many of which are beyond the Company’s control, that could cause actual results to differ materially from those expressed or implied. These risks and uncertainties include, among others, risks related to clinical development and the conduct, timing and results of clinical trials; the risk that results from preclinical studies, including comparisons with other product candidates or approved products, earlier clinical trials, modeling or other exploratory analyses may not be predictive of results in ongoing or future clinical trials; risks related to reliance on third parties for the supply of investigational agents used in combination studies; the Company’s cash position and anticipated cash runway; the Company’s need for additional financing; its limited operating history and history of operating losses; risks related to the integration of Faeth; the Company’s ability to satisfy applicable Nasdaq listing requirements and to maintain the listing of its common stock; and the other risks and uncertainties described under the headings “Risk Factors” and “Summary of Risk Factors” in the Company’s Annual Report on Form 10-K filed with the Securities and Exchange Commission (the “SEC”) on March 30, 2026, its Quarterly Report on Form 10-Q filed with the SEC on November 3, 2026, and its definitive proxy statement filed with the SEC on April 27, 2026, as well as in the Company’s subsequent filings. Forward-looking statements speak only as of the date of this press release, and the Company undertakes no obligation to update any forward-looking statement, except as required by law. Contacts Investor Contact: Matthew Biegler, SVP, Investor Relations matt@faeththerapeutics.com Media Contact: Patrick Schmidt, Consort Partners faeththerapeutics@consortpartners.com