治療胰腺癌，KRAS G12D抑制劑試驗(yàn)結(jié)果積極；針對膽管癌，創(chuàng)新溶酶體靶向藥物展現(xiàn)治療潛力…… | 一周盤點(diǎn)

本期看點(diǎn)：

1. 口服KRAS G12D（ON/OFF）抑制劑VS-7375用于治療晚期KRAS G12D突變實(shí)體瘤，在 一項(xiàng)1/2期臨床試驗(yàn)中獲積極初步數(shù)據(jù)。 93%接受單藥治療的轉(zhuǎn)移性胰腺導(dǎo)管癌（mPDAC）患者的腫瘤生物標(biāo)志物CA19-9水平下降超過50%。

2. 在研溶酶體靶向藥物GNS561在針對KRAS突變膽管癌患者的1b期臨床試驗(yàn)中取得了積極結(jié)果。約半數(shù)患者在第6周時達(dá)到疾病穩(wěn)定（SD），其中一名患者的SD狀態(tài)維持至第30周。

VS-7375：公布1/2期臨床試驗(yàn)的新數(shù)據(jù)

Verastem Oncology公司宣布了一項(xiàng)1/2期臨床試驗(yàn)的積極初步數(shù)據(jù)，該試驗(yàn)旨在評估口服KRAS G12D（ON/OFF）抑制劑VS-7375在晚期KRAS G12D突變實(shí)體瘤患者中的表現(xiàn)。VS-7375是一款口服KRAS G12D抑制劑，可與KRAS G12D的活化狀態(tài)和非活化狀態(tài)結(jié)合，從而更全面地抑制KRAS G12D信號和腫瘤生長。此次公布的數(shù)據(jù)涵蓋了mPDAC、轉(zhuǎn)移性結(jié)直腸癌（mCRC）和晚期非小細(xì)胞肺癌（NSCLC）等多個瘤種，證實(shí)了該藥物在多個劑量水平下均展現(xiàn)出令人鼓舞的臨床活性及良好的安全性。此外，Verastem公司還宣布計劃與Erasca公司合作，探索將VS-7375與Erasca在研的泛RAS分子膠ERAS-0015聯(lián)合用于KRASG12D突變實(shí)體瘤的潛在臨床評估。

此次公布的結(jié)果顯示，VS-7375的安全性和耐受性良好，主要表現(xiàn)為低級別胃腸道反應(yīng)，且多數(shù)在治療第一周期后顯著減輕；聯(lián)合用藥方案的耐受性也良好。在經(jīng)治mPDAC患者中，900 mg VS-7375單藥治療使93%（13/14）患者的腫瘤標(biāo)志物CA19-9下降超過50%；與西妥昔單抗的聯(lián)合用藥則帶來了更深、更快的腫瘤縮小；與標(biāo)準(zhǔn)化療（吉西他濱聯(lián)合白蛋白結(jié)合型紫杉醇）也表現(xiàn)出良好的相容性。在mCRC和NSCLC隊(duì)列中，該藥物也觀察到了積極的初步療效。

GNS561：公布1b期聯(lián)合治療試驗(yàn)數(shù)據(jù)

GENFIT公司宣布其在研溶酶體靶向藥物GNS561在針對KRAS突變膽管癌患者的1b期臨床試驗(yàn)中取得了積極結(jié)果。GNS561是一種靶向PPT1的小分子藥物，通過抑制自噬和誘導(dǎo)溶酶體功能障礙來破壞癌細(xì)胞生存機(jī)制，與MEK抑制劑聯(lián)用可協(xié)同阻斷自噬與MAPK信號通路。該研究旨在評估GNS561聯(lián)合曲美替尼在既往接受過一至二線標(biāo)準(zhǔn)治療失敗、亟需新療法的重度經(jīng)治膽管癌患者中的安全性與耐受性。

試驗(yàn)結(jié)果顯示，該聯(lián)合療法展現(xiàn)出良好的安全性和耐受性，未報告劑量限制性毒性（DLT），支持繼續(xù)推進(jìn)臨床開發(fā)。在抗腫瘤活性方面，約半數(shù)患者在第6周時達(dá)到SD，其中一名患者的SD狀態(tài)維持至第30周。基于這些積極數(shù)據(jù)，GENFIT決定在更高劑量水平下擴(kuò)展1b期研究以進(jìn)一步充實(shí)臨床數(shù)據(jù)集，同時計劃于今年夏季確定2期臨床試驗(yàn)的推薦劑量及研究方案，2期臨床試驗(yàn)仍按計劃將于2026年下半年啟動。

VK3019：啟動1期臨床試驗(yàn)

Viking Therapeutics公司宣布正式啟動其在研胰淀素與降鈣素受體雙重激動劑（DACRA）VK3019的1期臨床試驗(yàn)。VK3019正被開發(fā)為一種潛在的減重治療選擇，此次1期試驗(yàn)采用隨機(jī)、雙盲、安慰劑對照設(shè)計，納入身體質(zhì)量指數(shù)（BMI）≥30的健康成年受試者，主要評估VK3019單次皮下給藥后的安全性、耐受性和藥代動力學(xué)特征，同時探索單次給藥后體重變化的藥效動力學(xué)指標(biāo)。

Viking內(nèi)部開發(fā)的DACRAs的臨床前研究結(jié)果顯示，與接受對照治療的動物相比，該類化合物對健康大鼠和飲食誘導(dǎo)肥胖（DIO）小鼠的體重、食物攝入及代謝產(chǎn)生了顯著影響。在單次給藥后的0至72小時內(nèi)，這些化合物有效減少了瘦大鼠的食物攝入量；在給藥72小時時，與對照組相比，受試動物的體重降幅最高達(dá)8%。

參考資料：

[1] TScan Therapeutics Announces Positive Initial Data from Cohort C of Ongoing ALLOHA? Phase 1 Study Evaluating TSC-101 in Patients with Heme Malignancies Undergoing Allogeneic Hematopoietic Cell Transplantation. Retrieved June 26, 2026, from https://www.globenewswire.com/news-release/2026/06/22/3315162/0/en/tscan-therapeutics-announces-positive-initial-data-from-cohort-c-of-ongoing-alloha-phase-1-study-evaluating-tsc-101-in-patients-with-heme-malignancies-undergoing-allogeneic-hematop.html

[2] Taysha Gene Therapies Announces Completion of Dosing in REVEAL Pivotal Trial and Reports Longer-Term Clinical Data from Part A of REVEAL Phase 1/2 Trials Evaluating TSHA-102 for Rett Syndrome. Retrieved June 26, 2026, from https://www.globenewswire.com/news-release/2026/06/22/3315248/0/en/taysha-gene-therapies-announces-completion-of-dosing-in-reveal-pivotal-trial-and-reports-longer-term-clinical-data-from-part-a-of-reveal-phase-1-2-trials-evaluating-tsha-102-for-re.html

[3] Pheno Therapeutics Granted FDA IND Clearance for Lead Multiple Sclerosis Therapeutic Candidate PTD802. Retrieved June 26, 2026, from https://secure.businesswire.com/news/home/20260622772175/en/Pheno-Therapeutics-Granted-FDA-IND-Clearance-for-Lead-Multiple-Sclerosis-Therapeutic-Candidate-PTD802

[4] Prolium Bioscience Announces First Patient Dosed in its Multinational, Phase 1/2 Study of PRO-203 in Systemic Sclerosis, and Last Patient, Last Visit in an Investigator-Led Study of PRO-203 in Refractory Lupus Nephritis. Retrieved June 26, 2026, from https://www.globenewswire.com/news-release/2026/06/22/3315254/0/en/prolium-bioscience-announces-first-patient-dosed-in-its-multinational-phase-1-2-study-of-pro-203-in-systemic-sclerosis-and-last-patient-last-visit-in-an-investigator-led-study-of-p.html

[5] Kither Biotech successfully completes Phase 1 clinical trial of KIT2014, a novel inhaled peptide therapy for respiratory diseases. Retrieved June 26, 2026, from https://www.globenewswire.com/news-release/2026/06/19/3314633/0/en/kither-biotech-successfully-completes-phase-1-clinical-trial-of-kit2014-a-novel-inhaled-peptide-therapy-for-respiratory-diseases.html

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[13] Trace Neuroscience Initiates Global Clinical Development Program for TRCN-1023, an Antisense Oligonucleotide Designed to Restore UNC13A Function for the Treatment of ALS. Retrieved June 26, 2026, from https://secure.businesswire.com/news/home/20260622451252/en/Trace-Neuroscience-Initiates-Global-Clinical-Development-Program-for-TRCN-1023-an-Antisense-Oligonucleotide-Designed-to-Restore-UNC13A-Function-for-the-Treatment-of-ALS

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