“癌癥之王”疾病控制率近97%的口服小分子療法；客觀緩解率達85%的創新抗體療法…… | 一周盤點

本期看點

1. 口服KRAS G12D抑制劑VS-7375用于治療

KRAS

2. 靶向Clever-1的單克隆抗體bexmarilimab與阿扎胞苷聯用，治療初治高危骨髓增生異常綜合征（HR-MDS）患者的早期臨床試驗結果亮眼，ORR達85%，完全緩解（CR）率為45%。

3. 創新靶點抗體偶聯藥物（ADC）TUB-040在治療鉑類耐藥的高級別漿液性卵巢癌（PROC-HGSOC）患者的早期臨床研究中表現亮眼，DCR達96%。

VS-7375：公布1/2期臨床試驗的新數據

Verastem Oncology公司公布了口服KRAS G12D抑制劑VS-7375用于治療

KRAS

該研究共納入了66名患者，其中95.5%為IV期，且多數（68.2%）已接受過至少兩線的化療方案。截至2025年9月27日的數據，在每日600 mg的推薦2期劑量（RP2D）下，59名療效可評估的患者中，ORR達到40.7%，DCR達96.7%，其中91.5%的患者靶病灶縮小。觀察到4個月時的總生存（OS）率為92.2%，中位總生存期尚未達到，中位無進展生存期（PFS）為5.52個月。安全性方面，治療相關不良事件導致的停藥率低至3%，表明VS-7375的安全性可控。

Bexmarilimab：公布1/2期聯合治療試驗的新數據

Faron Pharmaceuticals公司宣布，其靶向Clever-1的單克隆抗體bexmarilimab的一項1/2期臨床試驗獲得了積極結果。該研究旨在評估bexmarilimab聯用阿扎胞苷治療初治高危骨髓增生異常綜合征和低甲基化劑（HMA）治療失敗的復發/難治性（r/r）HR-MDS患者的安全性和有效性。Bexmarilimab是Faron公司全資擁有的在研免疫療法，旨在通過靶向髓系細胞功能和激活免疫系統，克服對現有療法的耐藥性并優化臨床療效。Bexmarilimab能與巨噬細胞上的免疫抑制受體Clever-1結合，該受體有助于腫瘤生長和轉移（即幫助癌癥躲避免疫系統）。通過靶向巨噬細胞上的Clever-1受體，bexmarilimab可改變腫瘤微環境，將巨噬細胞從免疫抑制（M2）狀態重編程為免疫刺激（M1）狀態，上調干擾素的產生，啟動免疫系統攻擊腫瘤，使癌細胞對標準治療敏感。

此次公布的結果顯示，bexmarilimab聯合阿扎胞苷在初治和HMA治療失敗的HR-MDS患者中的ORR分別為85%和63%。在初治HR-MDS患者中，55%實現了骨髓原始細胞的完全清除。其中，基線骨髓原始細胞<5%的患者的ORR高達100%。HMA治療失敗的r/r MDS患者的中位總生存期為13.4個月。該研究中，23%的患者在治療后接受了造血干細胞移植（HSCT）。安全性方面，bexmarilimab聯合治療的耐受性良好，其安全性與阿扎胞苷單藥治療相似，甚至更好。

TUB-040：公布1/2a期臨床試驗數據

Tubulis公司公布了NAPISTAR1-01臨床1/2a期研究的積極臨床數據。該研究評估了公司主打抗體偶聯藥物TUB-040在鉑類耐藥的高級別漿液性卵巢癌患者中的療效與安全性。TUB-040是一種靶向NaPi2b抗原的IgG1抗體，通過Tubulis的專有P5偶聯技術連接拓撲異構酶I抑制劑exatecan，形成具有可切割連接子的ADC療法，設計用于治療高表達NaPi2b的卵巢癌和肺腺癌。

這次所公布的中期分析結果顯示，TUB-040已完成Tubulis專有Tubutecan平臺的臨床概念驗證（PoC），并確認NaPi2b是一個具有潛力的新型ADC靶點。分析顯示，TUB-040在未經過生物標志物篩選、曾接受過多線治療的鉑類耐藥卵巢癌患者中展現出顯著的抗腫瘤活性和良好的耐受性。在1.67–3.3 mg/kg劑量組中，總緩解率達到59%，確認總緩解率為50%，其中在2.5 mg/kg劑量下觀察到1例CR。在同一劑量區間，確認DCR為96%，在所有劑量組中總體確認DCR為91%。其中3.3 mg/kg組的療效數據仍在持續成熟中。此外，81%的患者在治療過程中展現CA-125應答。TUB-040在所有劑量水平下總體耐受性良好，大多數治療伴發不良事件為1級或2級。

ZW191：公布1期臨床試驗的初步數據

Zymeworks公司公布了其ADC療法ZW191治療晚期實體瘤的1期臨床試驗的初步結果。ZW191靶向葉酸受體α（FRα），該靶點在約75%的高級別漿液性卵巢癌和約70%的肺腺癌中表達。ZW191具有獨特的設計，可高效進入FRα陽性細胞，并釋放Zymeworks開發的具旁觀者效應的載荷——拓撲異構酶I抑制劑ZD06519。

截至2025年9月10日的數據，ZW191在鉑類耐藥卵巢癌、轉移性子宮內膜癌和轉移性非小細胞肺癌患者中展現出良好的初步療效和安全性。在所有療效可評估的患者中（n=27），ORR為44%；在婦科腫瘤患者中（n=24），ORR達50%，其中接受劑量區間為6.4mg/kg至9.6 mg/kg的患者的ORR為64%。在≥3.2 mg/kg的劑量組中均觀察到ZW191的療效，且不限于高FRα表達的腫瘤。安全性方面，ZW191表現出可控的安全性，劑量調整/延遲率低。

INCB161734：公布1期臨床試驗數據

Incyte公司公布了其候選藥物INCB161734用于治療攜帶

KRAS

KRAS

截至2025年8月1日的數據，在所有接受治療的患者中都表現出可控的安全性。在每日接受600 mg（n=25）和1200 mg（n=29）劑量INCB161734的胰腺導管腺癌患者中，ORR分別達20%和34%，DCR分別高達64%和86%。

參考資料：

[1] Incyte Announces Phase 1 Results for its TGFβR2×PD-1 Bispecific Antibody in Advanced Colorectal Cancer and KRAS G12D Inhibitor in Advanced Pancreatic Ductal Adenocarcinoma. Retrieved October 24, 2025, from https://investor.incyte.com/news-releases/news-release-details/incyte-announces-phase-1-results-its-tgfbr2pd-1-bispecific#:~:text=WILMINGTON%2C%20Del.%20--%20%28BUSINESS%20WIRE%29--Oct.%2019%2C%202025--%20Incyte,KRAS%20G12D%20mutations%2C%20specifically%20pancreatic%20ductal%20adenocarcinoma%20%28PDAC%29.

[2] Tubulis Presents First Clinical Data from Phase I/IIa Trial for TUB-040 in Platinum-Resistant Ovarian Cancer (PROC) at ESMO 2025. Retrieved October 24, 2025, from https://tubulis.com/news/tubulis-presents-first-clinical-data-from-phase-i-iia-trial-for-tub-040-in-platinum-resistant-ovarian-cancer-proc-at-esmo-2025/#:~:text=MUNICH%2C%20GERMANY%2C%20October%2019%2C%202025%20%E2%80%93%20Tubulis%20today,Medical%20Oncology%20%28ESMO%29%20Congress%202025%20in%20Berlin%2C%20Germany.

[3] Verastem Oncology Announces Updated Data from Partner GenFleet Therapeutics’ Phase 1/2 Monotherapy Study in China of GFH375 (VS-7375) in Advanced KRAS G12D Mutant Pancreatic Ductal Adenocarcinoma. Retrieved October 24, 2025, from https://investor.verastem.com/news-releases/news-release-details/verastem-oncology-announces-updated-data-partner-genfleet-0

[4] Aurion Biotech Achieves All Primary, Secondary, and Exploratory Endpoints in AURN001 Phase 1/2 CLARA Trial at 12 Months. Retrieved October 24, 2025, from https://aurionbiotech.com/aurion-biotech-achieves-all-primary-secondary-and-exploratory-endpoints-in-aurn001-phase-1-2-clara-trial/#:~:text=Seattle%2C%20WA%3B%20Cambridge%2C%20MA%3B%20Tokyo%2C%20Japan%20%E2%80%93%2018,with%20corneal%20edema%20secondary%20to%20corneal%20endothelial%20dysfunction.

[5] Celcuity Presents Updated Data at the 2025 ESMO Congress from Phase 1 Study Evaluating Gedatolisib Plus Darolutamide in Men with Metastatic Castration Resistant Prostate Cancer (“mCRPC”). Retrieved October 24, 2025, from https://www.celcuity.com/wp-content/uploads/2025/10/ESMO-Prostate-Cancer-Data.pdf

[6] CatalYm Presents Long-Term Phase 1/2a Data Confirming Sustained Responses with Visugromab in CPI-Refractory Tumors at ESMO 2025. Retrieved October 24, 2025, from https://www.catalym.com/catalym-presents-long-term-phase-1-2a-data-confirming-sustained-responses-with-visugromab-in-cpi-refractory-tumors-at-esmo-2025/#:~:text=Munich%2C%20Germany%20and%20San%20Francisco%2C%20USA%2C%20October%2020%2C,European%20Society%20of%20Medical%20Oncology%20%28ESMO%29%20Congress%202025.

[7] Iksuda presents encouraging IKS014 Phase 1 data at ESMO. Retrieved October 24, 2025, from https://www.iksuda.com/news-views/iksuda-presents-encouraging-iks014-phase-1-data-at-esmo/

[8] Updated BEXMAB Phase I/II Data Presented at ESMO 2025 Shows Further Improvement, Strengthening the Clinical Profile of Bexmarilimab in Treatment-Na?ve HR-MDS Patients. Retrieved October 24, 2025, from https://faron.com/releases-and-publications/updated-bexmab-phase-i-ii-data-presented-at-esmo-2025-shows-further-improvement-strengthening-the-clinical-profile-of-bexmarilimab-in-treatment-naive-hr-mds-patients/

[9] Perspective Therapeutics Presents Updated Interim Data from its Ongoing Phase 1/2a Clinical Trial of [212Pb]VMT-α-NET at the ESMO Congress 2025. Retrieved October 24, 2025, from https://www.globenewswire.com/news-release/2025/10/20/3169119/0/en/Perspective-Therapeutics-Presents-Updated-Interim-Data-from-its-Ongoing-Phase-1-2a-Clinical-Trial-of-212Pb-VMT-%CE%B1-NET-at-the-ESMO-Congress-2025.html

[10] BioAtla Presents Promising Interim Data from its Phase 1 Trial with BA3182 in Patients with Treatment Refractory Metastatic Adenocarcinoma at ESMO 2025. Retrieved October 24, 2025, from https://www.globenewswire.com/news-release/2025/10/20/3169303/0/en/BioAtla-Presents-Promising-Interim-Data-from-its-Phase-1-Trial-with-BA3182-in-Patients-with-Treatment-Refractory-Metastatic-Adenocarcinoma-at-ESMO-2025.html

[11] ???, ‘PLK1 TPD’ ????? 美1/2a? “IND ??”. Retrieved October 24, 2025, from https://www.biospectator.com/news/view/26671

[12] Olema Oncology Announces New Data from the Phase 1b/2 Trial of Palazestrant Plus Ribociclib in ER+/HER2- Metastatic Breast Cancer at ESMO 2025. Retrieved October 24, 2025, from https://www.globenewswire.com/news-release/2025/10/18/3168941/0/en/Olema-Oncology-Announces-New-Data-from-the-Phase-1b-2-Trial-of-Palazestrant-Plus-Ribociclib-in-ER-HER2-Metastatic-Breast-Cancer-at-ESMO-2025.html

[12] Nxera’s Partner Cancer Research UK Presents Data from Successfully Completed Phase 1 Clinical Trial of Cancer Immunotherapy Drug HTL0039732 at ESMO. Retrieved October 24, 2025, from https://www.globenewswire.com/news-release/2025/10/21/3169954/0/en/Nxera-s-Partner-Cancer-Research-UK-Presents-Data-from-Successfully-Completed-Phase-1-Clinical-Trial-of-Cancer-Immunotherapy-Drug-HTL0039732-at-ESMO.html

[13] AskBio Announces Publication in Nature Medicine of 12-month data from Phase 1 Trial of AB-1002 Gene Therapy in Participants with Congestive Heart Failure. Retrieved October 24, 2025, from https://www.globenewswire.com/news-release/2025/10/21/3170137/0/en/AskBio-Announces-Publication-in-Nature-Medicine-of-12-month-data-from-Phase-1-Trial-of-AB-1002-Gene-Therapy-in-Participants-with-Congestive-Heart-Failure.html

[14] Dynavax Presents Positive Topline Data from Part 1 of Phase 1/2 Trial for Shingles Vaccine Candidate at IDWeek 2025 and Announces Initiation of Part 2 of Trial. Retrieved October 24, 2025, from https://www.prnewswire.com/news-releases/dynavax-presents-positive-topline-data-from-part-1-of-phase-12-trial-for-shingles-vaccine-candidate-at-idweek-2025-and-announces-initiation-of-part-2-of-trial-302590508.html

[15] Parabilis Medicines Presents Clinical Data Demonstrating First-Ever Drugging of Key Cancer Driver with FOG-01. Retrieved October 24, 2025, from https://www.businesswire.com/news/home/20251017729691/en/Parabilis-Medicines-Presents-Clinical-Data-Demonstrating-First-Ever-Drugging-of-Key-Cancer-Driver-with-FOG-001

[16] Tango Therapeutics Announces $225 Million Financing. Retrieved October 23, 2025 from https://ir.tangotx.com/news-releases/news-release-details/tango-therapeutics-announces-225-million-financing

[17] Avacta Therapeutics Presents Compelling Phase 1a Data for Faridoxorubicin and the pre|CISION? Platform at the European Society of Medical Oncology Annual Congress. Retrieved October 23, 2025 from https://www.globenewswire.com/news-release/2025/10/19/3169020/0/en/Avacta-Therapeutics-Presents-Compelling-Phase-1a-Data-for-Faridoxorubicin-and-the-pre-CISION-Platform-at-the-European-Society-of-Medical-Oncology-Annual-Congress.html

[18] ALX Oncology Announces Preclinical Data and Phase 1 Trial-in-Progress Presentations of ALX2004, a Novel EGFR-Targeted ADC, at 2025 AACR-NCI-EORTC Conference. Retrieved October 24, 2025 from https://www.globenewswire.com/news-release/2025/10/23/3172323/0/en/ALX-Oncology-Announces-Preclinical-Data-and-Phase-1-Trial-in-Progress-Presentations-of-ALX2004-a-Novel-EGFR-Targeted-ADC-at-2025-AACR-NCI-EORTC-Conference.html

[19] Zymeworks Presents Initial Clinical Data from the Phase 1 trial of ZW191, an Antibody-Drug Conjugate Targeting Folate Receptor-? at AACR-NCI-EORTC Conference. Retrieved October 24, 2025 from https://www.globenewswire.com/news-release/2025/10/23/3172321/0/en/Zymeworks-Presents-Initial-Clinical-Data-from-the-Phase-1-trial-of-ZW191-an-Antibody-Drug-Conjugate-Targeting-Folate-Receptor-at-AACR-NCI-EORTC-Conference.html

[20] Aicuris Presents Positive Phase 2 Results for Pritelivir and Favorable Phase 1 Safety Data for AIC468 at ID Week 2025. Retrieved October 24, 2025 from https://www.globenewswire.com/news-release/2025/10/20/3169156/0/en/Aicuris-Presents-Positive-Phase-2-Results-for-Pritelivir-and-Favorable-Phase-1-Safety-Data-for-AIC468-at-ID-Week-2025.html

免責聲明：本文僅作信息交流之目的，文中觀點不代表藥明康德立場，亦不代表藥明康德支持或反對文中觀點。本文也不是治療方案推薦。如需獲得治療方案指導，請前往正規醫院就診。

版權說明：歡迎個人轉發至朋友圈，謝絕媒體或機構未經

授權以任何形式轉載至其他平臺。轉載授權請在「藥明康德」微信公眾號回復“轉載”，獲取轉載須知。