治疗胰腺癌，潜在“first-in-class”单抗公布临床进展；针对多种免疫疗法难治性实体瘤，小分子疗法临床结果积极…… | 一周盘点

本期看点：

1. 旨在克服肿瘤对化疗耐药的单克隆抗体NP137的1b期联合治疗试验结果积极，88%的局部晚期胰腺导管腺癌（PDAC）患者观察到肿瘤缩小。
2. 小分子抑制剂PLN-101095联用PD-1抑制剂治疗免疫检查点抑制剂（ICI）难治性晚期或转移性实体瘤患者的1期临床试验结果积极，3名确认缓解患者的基线靶病灶平均缩小89%。

NP137：公布1b期联合治疗试验数据

NETRIS Pharma公司宣布，其靶向netrin-1的单克隆抗体NP137在1b期临床试验LAPNET-01中取得积极成果，相关数据已发表于《自然》期刊。NP137是潜在“first-in-class”的抗netrin-1单抗，旨在通过阻断netrin-1来克服肿瘤对化疗的耐药性。该试验评估了NP137联用改良FOLFIRINOX化疗方案（mFOLFIRINOX）一线治疗局部晚期胰腺导管腺癌患者的效果。

此次公布的结果显示，在41名可评估患者中，客观缓解率（ORR）为29%，12名患者达到确认的部分缓解（PR），中位缓解持续时间为9.02个月，88%的患者观察到肿瘤缩小。中位随访时间为13.1个月时，接受联合治疗的患者中位无进展生存期（PFS）达到10.85个月，中位总生存期（OS）为16.43个月，并有23%的患者的肿瘤转化可接受手术治疗的状态。在肿瘤中neogenin（一种netrin-1受体）高表达的患者亚组中，中位PFS达15.65个月，手术转化率达40%，截至数据截止时，其12个月OS达到100%。安全性方面，联合治疗方案未表现出额外的明显不良反应，其安全性表现与单独使用化疗时的预期一致。

▲LAPNET-01试验的临床结果（图片来源：参考资料[14]）

PLN-101095：公布1期临床试验的新数据

Pliant Therapeutics公司公布了其正在进行的1期临床试验的新数据，该试验评估了PLN-101095联用PD-1抑制剂pembrolizumab治疗ICI难治性晚期或转移性实体瘤患者的效果。PLN-101095是Pliant Therapeutics公司开发的口服靶向整合素αvβ8和αvβ1的双重选择性小分子抑制剂，用于治疗对免疫检查点抑制剂耐药的实体瘤。TGF-β信号传导的增加被认为是肿瘤细胞对免疫检查点抑制剂耐药的潜在原因。PLN-101095靶向肿瘤微环境中表达的整合素αvβ8和αvβ1，能够调节TGF-β的活性，旨在恢复肿瘤对PD-1/PD-L1抑制剂的敏感性。

截至2026年2月27日的数据，PLN-101095联用pembrolizumab展现出令人鼓舞的抗肿瘤活性与良好的安全性。在胆管癌、非小细胞肺癌、黑色素瘤及头颈鳞癌患者中，1名患者获得确认的完全缓解（CR），2名患者获得确认的PR，1名患者获得未确认的PR。3名确认缓解患者的中位治疗时间为19个月，基线靶病灶平均缩小89%。安全性方面，PLN-101095在所有评估剂量中普遍耐受良好，最常见的治疗相关不良事件为1-2级皮疹，仅观察到1例3级不良事件，因不良事件导致停药的患者仅有2例。

ZW191：公布1期临床试验的新数据

Zymeworks公司公布了其ADC疗法ZW191治疗晚期实体瘤的1期临床试验的新数据。ZW191靶向叶酸受体α（FRα），该靶点在约75%的高级别浆液性卵巢癌和约70%的肺腺癌中表达。ZW191具有独特的设计，可高效进入FRα阳性细胞，并释放Zymeworks开发的具旁观者效应的载荷——拓扑异构酶I抑制剂ZD06519。

此次公布的结果显示，ZW191在接受过大量先前治疗的卵巢癌和子宫内膜癌患者中展现出令人鼓舞的抗肿瘤活性，无论FRα的表达如何。在接受6.4-9.6 mg/kg剂量的患者中，铂类耐药卵巢癌患者确认的ORR达61%，子宫内膜癌患者确认的ORR为57%，这些患者的疾病控制率（DCR）达100%。数据截止时，中位缓解持续时间尚未达到，卵巢癌和子宫内膜癌队列的中位PFS为7.6个月。此外，ZW191耐受性良好，总体安全性可控且无意外信号。

参考资料：

[1] Immunitas Presents Phase 1/2a Data Highlighting Anti-Tumor Activity of Novel Immunotherapy IMT-009 at AACR 2026 Annual Meeting. Retrieved April 24, 2026, from https://www.prnewswire.com/news-releases/immunitas-presents-phase-12a-data-highlighting-anti-tumor-activity-of-novel-immunotherapy-imt-009-at-aacr-2026-annual-meeting-302744884.html

[2] Pliant Therapeutics Announces Presentation of Updated Data from the Phase 1 Trial of PLN-101095 in Patients with ICI-Refractory Solid Tumors at the 2026 AACR Annual Meeting. Retrieved April 24, 2026, from https://www.globenewswire.com/news-release/2026/04/18/3276583/0/en/pliant-therapeutics-announces-presentation-of-updated-data-from-the-phase-1-trial-of-pln-101095-in-patients-with-ici-refractory-solid-tumors-at-the-2026-aacr-annual-meeting.html

[3] 지아이이노, 'CD80-IL2' 병용 1b/2상 "FDA IND 승인". Retrieved April 24, 2026, from https://www.biospectator.com/news/view/28478

[4] Verismo Therapeutics' Initial Clinical Data from STAR-101 Phase 1 Trial of SynKIR™-110 KIR-CAR Presented at AACR 2026 Plenary Session. Retrieved April 24, 2026, from https://www.prnewswire.com/news-releases/verismo-therapeutics-initial-clinical-data-from-star-101-phase-1-trial-of-synkir-110-kir-car-presented-at-aacr-2026-plenary-session-302747527.html

[5] BioAge Reports Positive Phase 1 Data for BGE-102, a Novel Oral NLRP3 Inhibitor, Demonstrating Potential Best-in-Class Reductions in hsCRP. Retrieved April 24, 2026, from https://www.globenewswire.com/news-release/2026/04/21/3277765/0/en/bioage-reports-positive-phase-1-data-for-bge-102-a-novel-oral-nlrp3-inhibitor-demonstrating-potential-best-in-class-reductions-in-hscrp.html

[6] Zymeworks Presents New Phase 1 Data for ZW191, a Folate Receptor Alpha-Targeting ADC at AACR Annual Meeting 2026. Retrieved April 24, 2026, from https://www.globenewswire.com/news-release/2026/04/21/3278571/0/en/zymeworks-presents-new-phase-1-data-for-zw191-a-folate-receptor-alpha-targeting-adc-at-aacr-annual-meeting-2026.html

[7] Pheast Therapeutics Reports Initial Phase 1a Data Showing Early Clinical Activity and Target Engagement for PHST001 at AACR 2026. Retrieved April 24, 2026, from https://www.globenewswire.com/news-release/2026/04/17/3276453/0/en/pheast-therapeutics-reports-initial-phase-1a-data-showing-early-clinical-activity-and-target-engagement-for-phst001-at-aacr-2026.html

[8] Akamis Bio Announces Encouraging Preliminary Results from the Phase 1b FORTRESS Study of NG-350A in Mismatch Repair-Proficient Locally Advanced Rectal Cancer. Retrieved April 24, 2026, from https://www.businesswire.com/news/home/20260417285259/en/Akamis-Bio-Announces-Encouraging-Preliminary-Results-from-the-Phase-1b-FORTRESS-Study-of-NG-350A-in-Mismatch-Repair-Proficient-Locally-Advanced-Rectal-Cancer

[9] Salubris Biotherapeutics Presents Phase 1/2 Dose Escalation and Expansion Cohort Data for JK06, 5T4-Targeted Antibody Drug Conjugate, at the American Association for Cancer Research Annual Meeting. Retrieved April 24, 2026, from https://www.salubrisbio.com/2026/04/17/salubris-biotherapeutics-announces-expansion-cohort-data-for-jk06-5t4-targeted-antibody-drug-conjugate-at-the-american-association-for-cancer-conference/

[10] PureTech Reports Positive Topline Data from Phase 1b Trial of LYT-200 in Relapsed/Refractory (R/R) High-Risk (HR) Myelodysplastic Syndrome (MDS) and R/R Acute Myeloid Leukemia (AML). Retrieved April 24, 2026, from https://www.businesswire.com/news/home/20260422885726/en/PureTech-Reports-Positive-Topline-Data-from-Phase-1b-Trial-of-LYT-200-in-RelapsedRefractory-RR-High-Risk-HR-Myelodysplastic-Syndrome-MDS-and-RR-Acute-Myeloid-Leukemia-AML

[11] NETRIS Pharma: Nature publishes positive pancreatic cancer Phase 1b data for NP137 anti-netrin-1 monoclonal antibody. Retrieved April 24, 2026, from https://www.netrispharma.com/actualites/netris-pharma-nature-publishes-positive-pancreatic-cancer-phase-1b-data-for-np137-anti-netrin-1-monoclonal-antibody/

[12] DemeRx Announces FDA Acceptance of IND Application to Advance DMX-1001 for the Treatment of Alcohol Use Disorder (AUD). Retrieved April 24, 2026, from https://www.businesswire.com/news/home/20260422651767/en/DemeRx-Announces-FDA-Acceptance-of-IND-Application-to-Advance-DMX-1001-for-the-Treatment-of-Alcohol-Use-Disorder-AUD

[13] Mozart Therapeutics Announces Positive Interim Phase 1 Data in Adults with Stage 3 Type I Diabetes. Retrieved April 24, 2026, from https://www.prnewswire.com/news-releases/mozart-therapeutics-announces-positive-interim-phase-1-data-in-adults-with-stage-3-type-i-diabetes-302750748.html

[14] Roth, G., Artru, P., Bouche, O. et al. Netrin1 blockade alleviates resistance to chemotherapy in pancreatic cancer. Nature (2026). https://doi.org/10.1038/s41586-026-10436-4

免责声明：本文仅作信息交流之目的，文中观点不代 表药 明康德立场，亦不代 表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。