Tipiracil Hydrochloride/Trifluridine

结直肠癌（CRC）是全球发病率位居前列的恶性肿瘤之一。目前，以氟尿嘧啶为基础的双药/三药化疗，联合抗血管内皮生长因子（VEGF）或抗表皮生长因子受体（EGFR）靶向治疗，已成为转移性结直肠癌（mCRC）一线和二线治疗的标准方案。然而，三线及以上治疗手段十分有限，仅有瑞戈非尼、TAS-102、贝伐单抗等少数选择，且普遍存在疾病控制率欠佳、治疗相关不良事件（TRAE）高发等问题，亟待创新疗法突破困境。 近期，中国武汉开展的一项II期临床试验带来突破性进展，首次证实通过调控肠道菌群，联合免疫及抗血管生成治疗，有望成为转移性结直肠癌（mCRC）后线治疗的新方向，为晚期患者带来新的希望与选择！ ▲截图源自“THE LANCET” 粪菌移植联合疗法引爆突破，MSS结直肠癌疾病控制率狂飙至95%，无癌生存期延长近10个月 本研究共纳入20例微卫星稳定型转移性结直肠癌（MSS mCRC）患者，中位年龄为62岁（范围：42-79岁）。患者基线特征显示：80%（16例）体能状态评分（ECOGPS）为1分；70%（14例）原发肿瘤位于左侧结肠或直肠；70%（14例）伴肝转移。所有患者均接受过至少二线全身治疗，其中55%（11例）接受过≥3线治疗；70%（14例）既往使用过抗VEGF/VEGFR药物（如贝伐单抗、瑞戈非尼等），45%（9例）接受过局部放疗。 入组后，患者接受粪便菌群移植（口服定制胶囊）联合替雷利珠单抗及呋喹替尼作为三线及以上治疗方案，中位随访时间13.7个月（4.9-26.0个月）。 结果显示：患者 中位无进展生存期（PFS）达9.6个月 （95%CI 4.1–15.1，详见下图A）。 中位总生存期（OS）为13.7个月 （95%CI 9.3–17.7，详见下图B）。中位治疗持续时间为7.5个周期（范围：3～18个周期）， 60%的患者出现靶病灶缩小。 ▲图源“eClinical Medicine”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 在意向治疗（ITT）人群中， 客观缓解率（ORR）为20%（95%CI5.7–43.7），疾病控制率（DCR）高达95%（95%CI 75.1-99.9） ，其中 ，4例患者达到部分缓解（PR）；15例患者达病情稳定（SD），中位缓解持续时间（DOR）为8.1个月 （95%CI 1.7–10.6）。 ▲图源“eClinical Medicine”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 其中，患者05的治疗效果尤为显著：经评估该患者达到 部分缓解（PR） ，其影像学及血清肿瘤标志物动态变化详见附图，为该疗法的临床价值提供了直观例证。 ▲图源“eClinical Medicine”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 肠道微生态成抗癌新战场，四大硬核手段帮助肿瘤患者重塑肠道菌群平衡 肠道菌群与人体构建起复杂而精密的共生网络，不仅深度参与宿主的代谢调控，更在免疫系统与神经系统的塑造中发挥关键作用。对于癌症患者而言，调节肠道菌群平衡已成为提升治疗效果、改善生活质量的重要策略。目前，主要可通过饮食干预、益生菌补充、抗生素治疗及粪便微生物组移植（FMT）四大途径实现肠道菌群的优化。 1、饮食干预：从源头调节菌群生态 生命早期增加膳食纤维与益生元摄入、减少红肉食用并维持健康体重，可有效降低肿瘤发生风险。研究表明，饮食结构的调整能在24-48小时内显著改变肠道微生物组成。然而，癌症患者常因口腔黏膜炎、味觉改变及厌食症等副作用，导致饮食干预的实施面临挑战。 2、益生菌补充：激活肠道健康防线 益生菌作为“活的非病原性微生物”，足量摄入可显著改善健康状况。部分益生菌菌株被证实能调节肠道菌群，增强癌症免疫治疗效果，减轻放化疗不良反应。临床研究显示，益生菌在结直肠癌、肝癌、肺癌等多种癌症治疗中，有助于提升预后，也获得跨国癌症支持治疗协会等权威指南的推荐，对预防结肠感染、重建肠道微生态平衡具有积极意义。 3、粪便微生物组移植（FMT）：千年智慧的现代转化 源自1700多年前中医理论的FMT，如今已成为前沿医学手段。该技术通过提取健康个体粪便中的菌群，制成菌液或胶囊，经内窥镜灌注、口服胶囊、结肠镜介入或灌肠等方式，将健康菌群移植至患者肠道，快速重建微生物多样性，用于治疗肠道内外疾病，为癌症患者提供了调节菌群的创新方案。 ▲图源“Front Immunol”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 小编寄语 总之，上述研究证实，粪便菌群移植联合替雷利珠单抗与呋喹替尼，作为三线及以上治疗方案，在难治性微卫星稳定型转移性结直肠癌（MSS mCRC）中展现出显著的抗肿瘤活性与可控的安全性，有效延长患者生存期。这一创新疗法通过调节肠道菌群优化微生态，进一步增强抗PD-1免疫治疗效果，为晚期结直肠癌患者提供了极具前景的治疗新选择。 不过，全球肿瘤医生网小编还要提醒广大癌友，一旦出现营养摄入不足或体重下降等问题，应及时寻求专业营养支持，可通过口服营养补充、肠外营养干预等方式改善机体状态。如需深入了解粪菌移植、肠道菌群调节或定制益生菌等前沿疗法，可将近期影像和病理检查结果、治疗经历等资料，提交至 全球肿瘤医生网医学部， 初步评估营养状况。 参考资料 [1]Zhao W,et al.Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215)[J]. EClinicalMedicine, 2023, 66. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00492-3/fulltext [2]Xu H,et al.Antitumor effects of fecal microbiota transplantation: Implications for microbiome modulation in cancer treatment. Front Immunol. 2022 Sep 13;13:949490. https://pmc.ncbi.nlm.nih.gov/articles/PMC9513044/ 本文为全球肿瘤医生网原创，未经授权严禁转载

- 28% confirmed response rate (5/18) per RECIST v1.1 in unselected patients across doses prioritized for expansion (7.2, 8.6 and 10 mg/kg Q3W) - - 3 of 7 evaluable patients (43%) with confirmed responses at upper expansion dose (10 mg/kg Q3W) - - Median progression free survival of 5.8 months as of April 7th 2025 data cutoff - - Encouraging initial safety profile with no dose limiting toxicities at data cutoff - - Planning Phase 2 study initiation in 1H 2026 - - Conference call on Monday, May 12 at 8:00 a.m. ET - SOUTH SAN FRANCISCO, Calif., May 12, 2025 (GLOBE NEWSWIRE) -- CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of masked, conditionally activated biologics, today announced positive interim Phase 1 data for its EpCAM PROBODY® ADC candidate, CX-2051, in advanced, late-line CRC. The data are as of an April 7th 2025 data cutoff from the ongoing CTMX-2051-101 Phase 1 study. “EpCAM is a high potential and broadly expressed cancer target that has been challenging to drug historically due to expression on normal tissues. We believe we have broken important new ground with our data announced today, which show potential for markedly improved outcomes for CRC patients,” said Sean McCarthy, D. Phil, chief executive officer and chairman of CytomX. “CX-2051 is showing impressive, durable anti-tumor activity in late line metastatic CRC, an area of high unmet need and a very difficult tumor to treat. Furthermore, CX-2051 has been generally well tolerated, highlighting the power of CytomX PROBODY® masking technology.” Dr. McCarthy added, “Importantly, we believe these results validate EpCAM as an oncology target and unlock a broad development opportunity for CX-2051 in CRC and potentially many other cancer types where EpCAM is expressed. We are excited to rapidly advance CX-2051 for the benefit of CRC patients and to explore the full potential of this novel ADC.” CX-2051 Phase 1a Interim Data Summary in Advanced, Late-line Colorectal Cancer The CTMX-2051-101 study was initiated in April 2024 with dose escalation proceeding through seven dose levels as of April 2025. 25 advanced metastatic CRC patients were treated with CX-2051 across dose levels 1 through 5 as of the April 7, 2025 data cutoff. CX-2051 was administered on a once every three week schedule (Q3W). The 2.4 mg/kg and 4.8 mg/kg doses were single patient dose escalation cohorts not anticipated to be therapeutically active. At the 7.2 mg/kg, 8.6 mg/kg, and 10 mg/kg doses, 23 patients were treated in total, 18 of whom were efficacy evaluable, having had at least one post-baseline tumor assessment as of the data cutoff. Patient Characteristics: The 25 patients enrolled in the study across dose levels 1 through 5 had previously received a median of 4 prior lines of therapy and all patients had previously been treated with irinotecan. 64% of patients had liver metastases, 64% had KRAS mutations, and 96% were microsatellite stable. Patients were not preselected based on EpCAM expression levels. Efficacy Results: As of the data cutoff, 18 patients were efficacy-evaluable at the expansion doses of 7.2 mg/kg, 8.6 mg/kg, and 10 mg/kg Q3W. Overall response rate (ORR): 28% of patients (5/18) achieved confirmed partial RECIST v. 1.1 responses. Overall response rates for currently approved therapies in 3rd line or later CRC are in the low to mid-single digit percentages1. At the 10 mg/kg dose, 3 of 7 evaluable patients (43%) achieved confirmed partial responses. The Disease Control Rate2 was 94% across the three dose groups (17/18). Durability: Median progression free survival was 5.8 months as of the data cutoff. 10 of 18 patients remained on study treatment as of the data of cutoff. 28% of patients (5/18) achieved confirmed partial RECIST v. 1.1 responses. Overall response rates for currently approved therapies in 3rd line or later CRC are in the low to mid-single digit percentages1. At the 10 mg/kg dose, 3 of 7 evaluable patients (43%) achieved confirmed partial responses. The Disease Control Rate2 was 94% across the three dose groups (17/18). Median progression free survival was 5.8 months as of the data cutoff. 10 of 18 patients remained on study treatment as of the data of cutoff. Safety Results: As of the data cutoff, 25 patients were evaluable for safety. CX-2051 was generally well-tolerated with manageable adverse events, with no observed dose limiting toxicities. Most treatment related adverse events (TRAEs) were Grade 1 or Grade 2 in severity. The most common reported TRAEs were diarrhea (18 patients, 5 Grade 3), nausea (11 patients, 1 Grade 3), vomiting (8 patients, No Grade 3), fatigue (8 patients, 1 Grade 3), anemia (5 patients, 3 Grade 3), hypokalemia (3 patients, 1 Grade 3), neutrophil count decrease (2 patients, 2 Grade 3) and neutropenia (2 patients, 1 Grade 3). TRAEs included serious adverse events in 5 patients (1 Grade 2, 4 Grade 3). No Grade 4 or 5 TRAEs were observed. No events of pancreatitis, interstitial lung disease or febrile neutropenia were reported at time of data cutoff. CX-2051 Phase 1 Dose Expansions Initiated: Dose expansions have been initiated at doses of 7.2 mg/kg, 8.6 mg/kg and 10 mg/kg Q3W. A total of 20 patients are expected to be enrolled at each dose level to inform the selection of recommended phase 2 dose. CX-2051 Anticipated Milestones: CX-2051 Monotherapy for Advanced Late-Line CRC: Additional Phase 1 data update by Q1 2026 Planning Phase 2 study initiation in 1H 2026 CX-2051 CRC Combinations: Potential to initiate CX-2051 combination studies in earlier lines of CRC in 2026 CX-2051 Pan-tumor Potential: Evaluate non-CRC, EpCAM-expressing tumor indications for potential Phase 1b study initiation in 2026 Additional Phase 1 data update by Q1 2026 Planning Phase 2 study initiation in 1H 2026 Potential to initiate CX-2051 combination studies in earlier lines of CRC in 2026 Evaluate non-CRC, EpCAM-expressing tumor indications for potential Phase 1b study initiation in 2026 CytomX Investor Event Information Additional details will be provided on the Company’s Investor Call on May 12, 2025 at 8 a.m. EST. Participants may access the live webcast of the conference call from the Events and Presentations page of CytomX’s website at https://ir.cytomx.com/events-and-presentations. Participants may register for the conference call here and are advised to do so at least 10 minutes prior to joining the call. An archived replay of the webcast will be available on the company’s website for at least 30 days. About CTMX-2051-101 Study Additional information about the CTMX-2051-101 study can be found here on clinicaltrials.gov. About CX-2051 (EpCAM PROBODY® ADC) CX-2051 is an investigational masked, conditionally activated ADC directed toward epithelial cell adhesion molecule (EpCAM) and armed with a topoisomerase-1 inhibitor payload. CX-2051 has potential applicability across multiple EpCAM-expressing epithelial cancers, including CRC, and was discovered in collaboration with ImmunoGen, now part of AbbVie. EpCAM (Epithelial Cell Adhesion Molecule) is a highly expressed but previously undruggable tumor antigen due to expression on normal tissues. CX-2051 is designed to open a therapeutic window for this high potential target and to deliver meaningful anti-cancer activity in solid tumors, including CRC. About CytomX Therapeutics CytomX is a clinical-stage, oncology-focused biopharmaceutical company focused on developing novel conditionally activated, masked biologics designed to be localized to the tumor microenvironment. By pioneering a novel pipeline of localized biologics, powered by its PROBODY® therapeutic platform, CytomX’s vision is to create safer, more effective therapies for the treatment of cancer. CytomX’s robust and differentiated pipeline comprises therapeutic candidates across multiple treatment modalities including antibody-drug conjugates (ADCs), T-cell engagers, and immune modulators such as cytokines. CytomX’s clinical-stage pipeline includes CX-2051 and CX-801. CX-2051 is a masked, conditionally activated ADC directed toward epithelial cell adhesion molecule (EpCAM), armed with a topoisomerase-1 inhibitor payload. CX-2051 has potential applicability across multiple EpCAM-expressing epithelial cancers, including CRC. CX-801 is a masked interferon alpha-2b PROBODY® cytokine with broad potential applicability in traditionally immuno-oncology sensitive as well as insensitive (cold) tumors. CytomX has established strategic collaborations with multiple leaders in oncology, including Amgen, Astellas, Bristol Myers Squibb, Regeneron and Moderna. For more information about CytomX and how it is working to make conditionally activated treatments the new standard-of-care in the fight against cancer, visit www.cytomx.com and follow us on LinkedIn and X (formerly Twitter). CytomX Therapeutics Forward-Looking Statements This press release includes forward-looking statements. Such forward-looking statements involve known and unknown risks, uncertainties and other important factors that are difficult to predict, may be beyond our control, and may cause the actual results, performance, or achievements to be materially different from any future results, performance or achievements expressed or implied in such statements, including those related to CX-2051. Accordingly, you should not rely on any of these forward-looking statements, including those relating to the potential benefits, safety and efficacy or progress of CytomX’s or any of its collaborative partners’ product candidates, including CX-2051 and CX-801, the potential benefits or applications of CytomX’s PROBODY® therapeutic platform, CytomX’s or its collaborative partners’ ability to develop and advance product candidates into and successfully complete clinical trials, including the ongoing and planned clinical trials of CX-2051 and CX-801 and the timing of initial and ongoing data availability for our clinical trials, including CX-2051 and CX-801, and other development milestones. Risks and uncertainties that contribute to the uncertain nature of the forward-looking statements include: the unproven nature of CytomX’s novel PROBODY® therapeutic technology; uncertainties around the Company’s ability to raise sufficient funds to carry out its planned research and development; CytomX’s clinical trial product candidates are in the initial stages of clinical development and its other product candidates are currently in preclinical development, and the process by which preclinical and clinical development could potentially lead to an approved product is long and subject to significant risks and uncertainties, including the possibility that the results of preclinical research and early clinical trials, including initial CX-2051 results, may not be predictive of future results; the possibility that CytomX’s clinical trials will not be successful; the possibility that current preclinical research may not result in additional product candidates; CytomX’s dependence on the success of CX-2051 and CX-801; CytomX’s reliance on third parties for the manufacture of the Company’s product candidates; possible regulatory developments in the United States and foreign countries, including China and the European Union; and the risk that we may incur higher costs than expected for research and development or unexpected costs and expenses or may not obtain expected savings from our announced restructuring. Additional applicable risks and uncertainties include those relating to our preclinical research and development, clinical development, and other risks identified under the heading "Risk Factors" included in CytomX’s Quarterly Report on Form 10-Q filed with the SEC on May 12, 2025. The forward-looking statements contained in this press release are based on information currently available to CytomX and speak only as of the date on which they are made. CytomX does not undertake and specifically disclaims any obligation to update any forward-looking statements, whether as a result of any new information, future events, changed circumstances or otherwise. PROBODY is a U.S. registered trademark of CytomX Therapeutics, Inc. All other trademarks are the properties of their respective owners. Company Contact: Chris Ogden SVP, Chief Financial Officer cogden@cytomx.com Investor Contact: Precision AQ (formerly Stern Investor Relations) Stephanie Ascher Stephanie.Ascher@precisionaq.com Media Contact: Redhouse Communications Teri Dahlman teri@redhousecomms.com 1 Lonsurf®, Fruzaqla®, Stivarga® package inserts 2 Disease Control Rate: Patients achieving a best response of stable disease, partial response, or complete response. Source: CytomX Therapeutics Inc.