本期看點(diǎn)：

1. 旨在克服腫瘤對化療耐藥的單克隆抗體NP137的1b期聯(lián)合治療試驗(yàn)結(jié)果積極，88%的局部晚期胰腺導(dǎo)管腺癌（PDAC）患者觀察到腫瘤縮小。
2. 小分子抑制劑PLN-101095聯(lián)用PD-1抑制劑治療免疫檢查點(diǎn)抑制劑（ICI）難治性晚期或轉(zhuǎn)移性實(shí)體瘤患者的1期臨床試驗(yàn)結(jié)果積極，3名確認(rèn)緩解患者的基線靶病灶平均縮小89%。

NP137：公布1b期聯(lián)合治療試驗(yàn)數(shù)據(jù)

NETRIS Pharma公司宣布，其靶向netrin-1的單克隆抗體NP137在1b期臨床試驗(yàn)LAPNET-01中取得積極成果，相關(guān)數(shù)據(jù)已發(fā)表于《自然》期刊。NP137是潛在“first-in-class”的抗netrin-1單抗，旨在通過阻斷netrin-1來克服腫瘤對化療的耐藥性。該試驗(yàn)評估了NP137聯(lián)用改良FOLFIRINOX化療方案（mFOLFIRINOX）一線治療局部晚期胰腺導(dǎo)管腺癌患者的效果。

此次公布的結(jié)果顯示，在41名可評估患者中，客觀緩解率（ORR）為29%，12名患者達(dá)到確認(rèn)的部分緩解（PR），中位緩解持續(xù)時(shí)間為9.02個(gè)月，88%的患者觀察到腫瘤縮小。中位隨訪時(shí)間為13.1個(gè)月時(shí)，接受聯(lián)合治療的患者中位無進(jìn)展生存期（PFS）達(dá)到10.85個(gè)月，中位總生存期（OS）為16.43個(gè)月，并有23%的患者的腫瘤轉(zhuǎn)化可接受手術(shù)治療的狀態(tài)。在腫瘤中neogenin（一種netrin-1受體）高表達(dá)的患者亞組中，中位PFS達(dá)15.65個(gè)月，手術(shù)轉(zhuǎn)化率達(dá)40%，截至數(shù)據(jù)截止時(shí)，其12個(gè)月OS達(dá)到100%。安全性方面，聯(lián)合治療方案未表現(xiàn)出額外的明顯不良反應(yīng)，其安全性表現(xiàn)與單獨(dú)使用化療時(shí)的預(yù)期一致。

▲LAPNET-01試驗(yàn)的臨床結(jié)果（圖片來源：參考資料[14]）

PLN-101095：公布1期臨床試驗(yàn)的新數(shù)據(jù)

Pliant Therapeutics公司公布了其正在進(jìn)行的1期臨床試驗(yàn)的新數(shù)據(jù)，該試驗(yàn)評估了PLN-101095聯(lián)用PD-1抑制劑pembrolizumab治療ICI難治性晚期或轉(zhuǎn)移性實(shí)體瘤患者的效果。PLN-101095是Pliant Therapeutics公司開發(fā)的口服靶向整合素αvβ8和αvβ1的雙重選擇性小分子抑制劑，用于治療對免疫檢查點(diǎn)抑制劑耐藥的實(shí)體瘤。TGF-β信號傳導(dǎo)的增加被認(rèn)為是腫瘤細(xì)胞對免疫檢查點(diǎn)抑制劑耐藥的潛在原因。PLN-101095靶向腫瘤微環(huán)境中表達(dá)的整合素αvβ8和αvβ1，能夠調(diào)節(jié)TGF-β的活性，旨在恢復(fù)腫瘤對PD-1/PD-L1抑制劑的敏感性。

截至2026年2月27日的數(shù)據(jù)，PLN-101095聯(lián)用pembrolizumab展現(xiàn)出令人鼓舞的抗腫瘤活性與良好的安全性。在膽管癌、非小細(xì)胞肺癌、黑色素瘤及頭頸鱗癌患者中，1名患者獲得確認(rèn)的完全緩解（CR），2名患者獲得確認(rèn)的PR，1名患者獲得未確認(rèn)的PR。3名確認(rèn)緩解患者的中位治療時(shí)間為19個(gè)月，基線靶病灶平均縮小89%。安全性方面，PLN-101095在所有評估劑量中普遍耐受良好，最常見的治療相關(guān)不良事件為1-2級皮疹，僅觀察到1例3級不良事件，因不良事件導(dǎo)致停藥的患者僅有2例。

ZW191：公布1期臨床試驗(yàn)的新數(shù)據(jù)

Zymeworks公司公布了其ADC療法ZW191治療晚期實(shí)體瘤的1期臨床試驗(yàn)的新數(shù)據(jù)。ZW191靶向葉酸受體α（FRα），該靶點(diǎn)在約75%的高級別漿液性卵巢癌和約70%的肺腺癌中表達(dá)。ZW191具有獨(dú)特的設(shè)計(jì)，可高效進(jìn)入FRα陽性細(xì)胞，并釋放Zymeworks開發(fā)的具旁觀者效應(yīng)的載荷——拓?fù)洚悩?gòu)酶I抑制劑ZD06519。

此次公布的結(jié)果顯示，ZW191在接受過大量先前治療的卵巢癌和子宮內(nèi)膜癌患者中展現(xiàn)出令人鼓舞的抗腫瘤活性，無論FRα的表達(dá)如何。在接受6.4-9.6 mg/kg劑量的患者中，鉑類耐藥卵巢癌患者確認(rèn)的ORR達(dá)61%，子宮內(nèi)膜癌患者確認(rèn)的ORR為57%，這些患者的疾病控制率（DCR）達(dá)100%。數(shù)據(jù)截止時(shí)，中位緩解持續(xù)時(shí)間尚未達(dá)到，卵巢癌和子宮內(nèi)膜癌隊(duì)列的中位PFS為7.6個(gè)月。此外，ZW191耐受性良好，總體安全性可控且無意外信號。

參考資料：

[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] ?????, 'CD80-IL2' ?? 1b/2? "FDA IND ??". 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

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