針對血液腫瘤，多款蛋白降解療法進展積極；潛在“best-in-class”小分子激酶抑制劑公布早期臨床結果…… | 一周盤點

本期看點：

1. 潛在“best-in-class”布魯頓酪氨酸激酶（BTK）降解劑bexobrutideg（NX-5948）1期臨床試驗結果發布，中位隨訪時間為22.4個月時，慢性淋巴細胞白血病（CLL）患者的中位無進展生存期（PFS）為22.1個月，客觀緩解率（ORR）為83.0%。

2. IKZF1/3分子膠降解劑cemsidomide聯合地塞米松治療復發/難治性多發性骨髓瘤（RRMM）的最新分析結果發布，推薦2期劑量/最大耐受劑量下的ORR為53%。

Bexobrutideg：公布1a/b期臨床試驗的新數據

Nurix Therapeutics公布了其進行的NX-5948-301 1a/b期臨床試驗的更新臨床數據。該試驗正在評估其在研BTK降解劑bexobrutideg用于治療慢性淋巴細胞白血病患者的療效。Bexobrutideg是一款具有口服生物利用度、具有腦滲透性的在研小分子BTK降解劑，由Nurix和羅氏（Roche）開發。新聞稿指出，它有望成為用于腫瘤、免疫和神經系統疾病領域的潛在“best-in-class”療法。

截至2026年1月1日數據截止時，中位隨訪時間為22.4個月；患者的中位PFS為22.1個月（95% CI：14.0–NR），ORR為83.0%（95% CI：69.2–92.4）；緩解包括2例完全緩解（CR）、1例淋巴結部分緩解（nPR）和36例PR。在攜帶BTK抑制劑耐藥突變、具有高危分子特征以及存在中樞神經系統（CNS）受累的患者中均觀察到緩解。

Nurix還公布了來自兩個1b期隊列的新數據，這兩個隊列評估了bexobrutideg在較早線治療中的表現，包括既往接受過BTK抑制劑治療但未接受過BCL2抑制劑治療的患者（隊列5），以及未接受過BTK抑制劑治療的患者，包括初治患者（隊列15）。在隊列5（n=19）中，可評估患者（n=14）的ORR為92.9%（95% CI：66.1–99.8）。在隊列15（n=20）中，可評估患者（n=19）的ORR為84.2%（95% CI：60.4–96.6）。

Cemsidomide：公布1期臨床試驗數據

C4 Therapeutics公司公布了其已完成入組的cemsidomide 1期臨床試驗的進一步分析結果。Cemsidomide是一款下一代口服IKZF1/3降解劑，IKZF1/3是多發性骨髓瘤生物學中的關鍵轉錄因子。該試驗評估其聯合地塞米松治療復發/難治性多發性骨髓瘤（RRMM）的療效。

數據截止日期為2026年2月27日，參與試驗的患者此前接受過大量治療，既往治療線數中位數為7線。在推薦2期劑量/最大耐受劑量（100 μg）下，cemsidomide達到53%的ORR。在75 μg劑量水平下，cemsidomide達到40%的ORR。在所有評估劑量中，cemsidomide達到36%的ORR。

關鍵新數據顯示，在cemsidomide 75 μg和100 μg劑量水平下，患者緩解程度隨時間進一步加深。

• 在75 μg劑量水平下，1例此前最佳緩解為PR的患者加深至非常好的部分緩解（VGPR）。

• 在100 μg劑量水平下，多例患者實現更深緩解：1例此前最佳緩解為PR的患者加深至嚴格完全緩解（sCR）；1例此前最佳緩解為PR的患者加深至VGPR。

• 在100 μg劑量水平下，2例達到sCR和CR的患者實現微小殘留病（MRD）陰性。

ELVN-001：公布1期臨床試驗的新數據

Enliven Therapeutics公司公布其小分子激酶抑制劑ELVN-001的1期ENABLE臨床試驗的新數據，該研究旨在評估ELVN-001對現有酪氨酸激酶抑制劑（TKI）不耐受、復發或難治的慢性髓系白血病（CML）患者的療效。ELVN-001是一種強效、高選擇性、潛在“best-in-class”的小分子激酶抑制劑，專門針對CML患者的致癌驅動因子BCR-ABL1融合蛋白。ELVN-001還具有針對耐藥性最強的BCR-ABL1耐藥突變體T315I和其他已知耐藥突變體的活性。

截至2026年3月10日的數據，在每日一次80 mg劑量組中，總主要分子學緩解率（MMR）達61%，在24周時的MMR率為48%，深度分子緩解（DMR）達成率為30%。對于既往僅接受過1-2種TKI治療的患者，總MMR為67%，24周時的MMR率為55%。安全性方面，ELVN-001整體耐受性良好，因不良事件停藥的比例為6%，多數治療伴發不良事件為1-2級。

▲ENABLE試驗的研究結果（圖片來源：參考資料[13]）

Briumvi（ublituximab）：公布1期臨床試驗數據

TG Therapeutics公司公布了其皮下注射的Briumvi治療重癥肌無力（MG）的積極1期臨床試驗數據，并啟動了一項2期臨床試驗。Briumvi是一種靶向CD20表達B細胞上獨特表位的新型單克隆抗體，通過糖基工程改造去除了抗體上通常表達的某些糖分子，從而能夠在低劑量下實現高效的B細胞耗竭。

此次公布的結果顯示，82%的患者在第24周達到了重癥肌無力日常生活活動（MG-ADL）評分的最小臨床重要差異（MCID，定義為下降≥2分）。總體而言，第24周觀察到MG-ADL評分平均改善4.6分。該療法耐受性良好，安全性特征與靜脈注射的Briumvi在多發性硬化中的已知安全性一致。

參考資料：

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[2] Antag Therapeutics presents positive Phase 1 results at the 2026 Scientific Sessions of the American Diabetes Association for AT7687, a first-in-class GIPR antagonist. Retrieved June 12, 2026, from https://www.globenewswire.com/news-release/2026/06/07/3307739/0/en/antag-therapeutics-presents-positive-phase-1-results-at-the-2026-scientific-sessions-of-the-american-diabetes-association-for-at7687-a-first-in-class-gipr-antagonist.html

[3] Amphista Therapeutics announces FDA clearance of IND application for AMX-883, its lead Targeted Glue? degrader for acute myeloid leukaemia. Retrieved June 12, 2026, from https://www.globenewswire.com/news-release/2026/06/08/3307957/0/en/amphista-therapeutics-announces-fda-clearance-of-ind-application-for-amx-883-its-lead-targeted-glue-degrader-for-acute-myeloid-leukaemia.html

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[5] Lifordi Immunotherapeutics Presents Phase 1 Clinical Data for LFD-200, a Subcutaneous Glucocorticoid Antibody Drug Conjugate, at EULAR 2026. Retrieved June 12, 2026, from https://www.newsfilecorp.com/release/300497

[6] Atavistik Bio Announces U.S. FDA Clearance of Investigational New Drug Application and Fast Track Designation for ATV-1601 for the Treatment of Hereditary Hemorrhagic Telangiectasia (HHT). Retrieved June 12, 2026, from https://www.globenewswire.com/news-release/2026/06/09/3308700/0/en/atavistik-bio-announces-u-s-fda-clearance-of-investigational-new-drug-application-and-fast-track-designation-for-atv-1601-for-the-treatment-of-hereditary-hemorrhagic-telangiectasia.html

[7] Kymera Therapeutics Announces First Participant Dosed in Phase 1 Trial of Oral IRAK4 Degrader, KT-485, and Milestone Achievement Under Sanofi Collaboration. Retrieved June 12, 2026, from https://www.globenewswire.com/news-release/2026/06/09/3308699/0/en/kymera-therapeutics-announces-first-participant-dosed-in-phase-1-trial-of-oral-irak4-degrader-kt-485-and-milestone-achievement-under-sanofi-collaboration.html

[8] TG Therapeutics Announces Positive Topline Phase 1 Data for Subcutaneous BRIUMVI in Patients with Myasthenia Gravis and Initiation of Potential Registration Directed Randomized Phase 2 Trial. Retrieved June 12, 2026, from https://www.globenewswire.com/news-release/2026/06/09/3308725/8790/en/tg-therapeutics-announces-positive-topline-phase-1-data-for-subcutaneous-briumvi-in-patients-with-myasthenia-gravis-and-initiation-of-potential-registration-directed-randomized-pha.html

[9] Imviva Biotech Receives FDA Investigational New Drug Approval for CTA313, a Dual-Targeted CD19/BCMA Allogeneic CAR-T Cell Therapy for Autoimmune Diseases. Retrieved June 12, 2026, from https://www.globenewswire.com/news-release/2026/06/09/3308823/0/en/imviva-biotech-receives-fda-investigational-new-drug-approval-for-cta313-a-dual-targeted-cd19-bcma-allogeneic-car-t-cell-therapy-for-autoimmune-diseases.html

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[13] Enliven Therapeutics Announces Updated Positive Phase 1 Clinical Data and Alignment with FDA on Key Phase 3 Trial Design Components. Retrieved June 12, 2026, from https://www.prnewswire.com/news-releases/enliven-therapeutics-announces-updated-positive-phase-1-clinical-data-and-alignment-with-fda-on-key-phase-3-trial-design-components-302797424.html

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[15] C4 Therapeutics Presents Phase 1 Data at European Hematology Association (EHA) 2026 Congress Highlighting Cemsidomide as a Potential Best-in-Class IKZF1/3 Degrader for Multiple Myeloma in Heavily Pretreated Relapsed/Refractory Population. Retrieved June 12, 2026, from https://www.globenewswire.com/news-release/2026/06/11/3310320/0/en/c4-therapeutics-presents-phase-1-data-at-european-hematology-association-eha-2026-congress-highlighting-cemsidomide-as-a-potential-best-in-class-ikzf1-3-degrader-for-multiple-myelo.html

[16] Climb Bio Announces Initial Phase 1b Data Demonstrating On-Target Clinical Activity for Budoprutug in Immune Thrombocytopenia at EHA Congress 2026. Retrieved June 12, 2026, from https://www.globenewswire.com/news-release/2026/06/11/3310326/0/en/climb-bio-announces-initial-phase-1b-data-demonstrating-on-target-clinical-activity-for-budoprutug-in-immune-thrombocytopenia-at-eha-congress-2026.html

[17] Nurix Therapeutics to Report Updated Phase 1a/b Results for BTK Degrader Bexobrutideg, Highlighting Durable Responses in Relapsed/Refractory CLL/SLL and Promising Activity in Earlier Lines of Therapy. Retrieved June 12, 2026, from https://www.globenewswire.com/news-release/2026/06/11/3310331/0/en/nurix-therapeutics-to-report-updated-phase-1a-b-results-for-btk-degrader-bexobrutideg-highlighting-durable-responses-in-relapsed-refractory-cll-sll-and-promising-activity-in-earlie.html

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