多款小分子使70%特定患者肿瘤缩小；对多种恶性肿瘤有效的多KRAS抑制剂…… | 一周盘点|fx|单药|多kras抑制剂|实体瘤|恶性肿瘤|活性|癌症|肿瘤细胞

本期看点

1. 小分子

MYB

mRNA 降解剂REM-422用于治疗复发或转移性腺样囊性癌（R/M ACC）的早期临床试验结果亮眼，在生物标志物阳性患者亚组中，超过70%的患者肿瘤缩小超20%。

2. 潜在"first-in-class"的口服PPARγ靶向小分子抑制剂FX-909在一项用于治疗局部晚期或转移性尿路上皮癌（UC）的1期临床试验中，使70% PPARγ高表达患者的肿瘤缩小。

3. 具有KRAS G12D偏好活性的多KRAS抑制剂QTX3034在一项早期临床试验中显示出对多种恶性肿瘤的抗肿瘤活性，且分子层面的强效反应（

KRAS

G12D ctDNA减少>90%）与抗肿瘤活性密切相关。

REM-422：公布1期临床试验的初步数据

Remix Therapeutics公司宣布了其潜在“first-in-class”的

MYB

mRNA降解剂REM-422用于治疗复发或转移性腺样囊性癌的初步1期临床试验结果。

MYB

是多种实体瘤和血液恶性肿瘤的致癌驱动因子。REM-422是一种强效、选择性口服小分子mRNA降解剂，通过促进mRNA转录本掺入毒性外显子，引发无义介导的mRNA降解（NMD），可减少MYBmRNA及随后的蛋白表达，从而在MYB依赖性人类肿瘤模型中产生抗肿瘤活性。该药物已获得美国FDA针对ACC和急性髓系白血病（AML）的孤儿药资格，并正在开展针对ACC和AML或高危骨髓增生异常综合征（HR-MDS）的1期临床研究。

截至2025年10月1日的数据，在疗效人群中，REM-422的总缓解率（ORR）为43%（基于RECIST标准）。在接受研究超过6个月的生物标志物阳性患者亚组中，71%（10/14）的肿瘤缩小超过20%，其中6例部分缓解（PR）患者在4-6个月时仍持续缓解。药物的总体耐受性良好，最常见的治疗相关不良事件为贫血、疲劳和鼻出血。

FX-909：公布1期临床试验数据

Flare Therapeutics公司宣布了其在研新药FX-909用于治疗局部晚期或转移性尿路上皮癌的1期临床研究的A部分数据。FX-909是一种靶向PPARγ、潜在"first-in-class"的口服小分子抑制剂。该研究是一项开放标签的剂量递增试验，评估了FX-909在28天周期内每日口服一次的安全性、耐受性、药代动力学（PK）、药效动力学（PD）及初步临床活性，共入组了46名晚期实体瘤患者，其中36名为晚期UC患者。

截至2025年9月17日的数据，FX-909在所有剂量组的晚期UC患者中均显示出初步的抗肿瘤活性，包括4例PR和1例完全缓解（CR），且具有可接受的安全性和耐受性。疗效在PPARγ高表达的患者中尤为显著，在20例此类患者中，70%观察到肿瘤缩小。

QTX3034：公布1期临床试验数据

Quanta Therapeutics公司宣布了其具有KRAS G12D偏好活性的多KRAS抑制剂QTX3034的1期临床试验数据。该疗法目前正在进行一项针对

KRAS

G12D突变实体瘤患者的1期临床试验。该研究同时评估了QTX3034作为单药以及与广泛使用的EGFR抑制剂西妥昔单抗联合用药的安全性、耐受性及初步疗效，入组患者包括晚期结直肠癌（CRC）、胰腺导管腺癌（PDAC）和子宫内膜癌患者。

截至2025年9月23日的数据，无论是单药还是与西妥昔单抗联合，QTX3034均表现出良好的安全性和明确的临床概念验证。在推荐的2期剂量（RP2D）下，接受QTX3034单药治疗的经过多线治疗的晚期子宫内膜癌患者有缓解，包括确认的CR。联合治疗方案在难治性CRC和PDAC患者中也显示出显著的抗肿瘤活性，包括4例PR。安全性方面，药物耐受性良好，不良事件多为低级别且可控，未观察到剂量限制性毒性（DLT）或≥3级的治疗相关不良事件。药代动力学数据显示药物口服吸收良好，且分子层面的强效反应（KRASG12D ctDNA减少>90%）与抗肿瘤活性密切相关。这些结果支持当前正在进行的剂量扩展研究，并为后续与标准化疗方案的联合应用提供了依据。

参考资料：

[1] Citryll Presents Positive Data from Phase I Study of CIT-013 in Rheumatoid Arthritis at ACR Convergence 2025. Retrieved October 31, 2025, from https://www.globenewswire.com/news-release/2025/10/27/3174302/0/en/Citryll-Presents-Positive-Data-from-Phase-I-Study-of-CIT-013-in-Rheumatoid-Arthritis-at-ACR-Convergence-2025.html

[2] Bristol Myers Squibb Presents Encouraging Data from Phase 1 Breakfree-1 Study of CD19 NEX-T™ CAR T Cell Therapy in Three Chronic Autoimmune Diseases at ACR Convergence 2025. Retrieved October 31, 2025, from https://www.businesswire.com/news/home/20251024606817/en/Bristol-Myers-Squibb-Presents-Encouraging-Data-from-Phase-1-Breakfree-1-Study-of-CD19-NEX-T-CAR-T-Cell-Therapy-in-Three-Chronic-Autoimmune-Diseases-at-ACR-Convergence-2025

[3] Kyverna Therapeutics Highlights Potential of KYV-101 in Rheumatoid Arthritis with Phase 1 Data from Investigator-Initiated Trial Presented at ACR Convergence 2025. Retrieved October 31, 2025, from https://ir.kyvernatx.com/news-releases/news-release-details/kyverna-therapeutics-highlights-potential-kyv-101-rheumatoid

[4] MicrobiotiX Receives IND Approval for Novel Bacteriophage Drug MP101. Retrieved October 31, 2025, from https://www.globenewswire.com/news-release/2025/10/27/3174461/0/en/MicrobiotiX-Receives-IND-Approval-for-Novel-Bacteriophage-Drug-MP101.html

[5] Flare Therapeutics Presents Part A Data from FX-909 Phase 1 Study at AACR-NCI-EORTC International Conference. Retrieved October 31, 2025, from https://www.globenewswire.com/news-release/2025/10/24/3172983/0/en/Flare-Therapeutics-Presents-Part-A-Data-from-FX-909-Phase-1-Study-at-AACR-NCI-EORTC-International-Conference.html

[6] Remix Therapeutics Announces Positive Preliminary Data from Phase 1 Study of REM-422 in Patients with Adenoid Cystic Carcinoma at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. Retrieved October 31, 2025, from https://www.globenewswire.com/news-release/2025/10/24/3172910/0/en/Remix-Therapeutics-Announces-Positive-Preliminary-Data-from-Phase-1-Study-of-REM-422-in-Patients-with-Adenoid-Cystic-Carcinoma-at-the-2025-AACR-NCI-EORTC-International-Conference-o.html

[7] Biomea Fusion Announces First Patient Dosed in Phase I Study of BMF-650 a Next-Generation Oral GLP-1 Receptor Agonist. Retrieved October 31, 2025, from https://www.globenewswire.com/news-release/2025/10/27/3174503/0/en/Biomea-Fusion-Announces-First-Patient-Dosed-in-Phase-I-Study-of-BMF-650-a-Next-Generation-Oral-GLP-1-Receptor-Agonist.html

[8] Lifordi Immunotherapeutics Presents Nonclinical Data on Glucocorticoid Antibody Drug Conjugate LFD-200 at ACR 2025 and Initiates Phase 1 Study in Rheumatoid Arthritis. Retrieved October 31, 2025, from https://www.newsfilecorp.com/release/272018

[9] Concerto Biosciences Announces Positive Topline Results from Phase 1b Clinical Trial of ENS-002 in Patients with Atopic Dermatitis. Retrieved October 31, 2025, from https://www.prnewswire.com/news-releases/concerto-biosciences-announces-positive-topline-results-from-phase-1b-clinical-trial-of-ens-002-in-patients-with-atopic-dermatitis-302596913.html

[10] Sonoma Biotherapeutics Announces Positive Interim Safety and Efficacy Data from Phase 1 REGULATE-RA Study of SBT-77-7101 in Refractory Rheumatoid Arthritis. Retrieved October 29, 2025 from https://www.businesswire.com/news/home/20251029046316/en/Sonoma-Biotherapeutics-Announces-Positive-Interim-Safety-and-Efficacy-Data-from-Phase-1-REGULATE-RA-Study-of-SBT-77-7101-in-Refractory-Rheumatoid-Arthritis

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[12] Quanta Therapeutics Presents Positive Phase 1 Data for QTX3034, an Oral G12D-Preferring Multi-KRAS Inhibitor, in Patients with Advanced Solid Tumors. Retrieved October 31, 2025, from https://www.globenewswire.com/news-release/2025/10/24/3172963/0/en/Quanta-Therapeutics-Presents-Positive-Phase-1-Data-for-QTX3034-an-Oral-G12D-Preferring-Multi-KRAS-Inhibitor-in-Patients-with-Advanced-Solid-Tumors.html

[13] Sionna Therapeutics Announces Presentation of SION-719 and SION-451 Phase 1 Data and Poster of New Preclinical Data on the Impact of NBD1 Stabilizers on F508del-CFTR Half-Life at the 2025 North American Cystic Fibrosis Conference. Retrieved October 31, 2025, from https://www.globenewswire.com/news-release/2025/10/24/3173007/0/en/Sionna-Therapeutics-Announces-Presentation-of-SION-719-and-SION-451-Phase-1-Data-and-Poster-of-New-Preclinical-Data-on-the-Impact-of-NBD1-Stabilizers-on-F508del-CFTR-Half-Life-at-t.html

[14] Celldex Announces Initial Positive Results from Phase 1 Trial of CDX-622 Demonstrating Favorable Safety and PK Profile and Sustained Mast Cell Inhibition. Retrieved October 31, 2025, from https://www.globenewswire.com/news-release/2025/10/30/3177884/24180/en/Celldex-Announces-Initial-Positive-Results-from-Phase-1-Trial-of-CDX-622-Demonstrating-Favorable-Safety-and-PK-Profile-and-Sustained-Mast-Cell-Inhibition.html

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