PO.CT01.02 · 临床试验

MK-2010（一种PD-1×VEGF双特异性抗体）首次人体研究的初步结果

Preliminary results from the first-in-human study of MK-2010, a PD-1×VEGF bispecific antibody

编号 CT057 展板 17 时间 4/20 09:00–12:00 区域 Section 50 主讲 Jennifer Pawlowski

分会场 First-in-Human Phase I Clinical Trials

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作者与单位 Authors & Affiliations

Jin Li¹, Weizheng Kou², Longhua Sun³, Yanqiu Zhao⁴, Rusen Zhao⁵, Baozhong Wang⁶, Shaozhang Zhou⁷, Juan Li⁸, Xuewen Liu⁹, Jun Zhao¹⁰, Dongqing Lv¹¹, Gaofeng Li¹², Junli Xue¹³, Yong Fang¹⁴, Daren Lin¹⁵, Jianhua Shi¹⁶, Yi Gong¹⁷, Xia Qin¹⁸, Yi Zuo¹⁹, Erik H. Knelson²⁰, Weijuan Zhang¹⁹, Caicun Zhou¹³

¹Shanghai GoBroad Cancer Hospital, China Pharmaceutical University, Shanghai, China,²The First Affiliated Hospital of Xinxiang Medical University, Xixiang, China,³The First Affiliated Hospital of Nanchang University, Nanchang, China,⁴The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China,⁵Zibo Municipal Hospital, Zibo, Shandong, China,⁶Liaocheng People's Hospital, Liaocheng, China,⁷Guangxi Medical University Cancer Hospital, Nanning, China,⁸Sichuan Cancer Hospital, Sichuan, China,⁹The Third Xiangya Hospital of Central South University, Changsha, China,¹⁰Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department I of Thoracic Oncology, Peking University Cancer Hospital and Institute, Beijing, China,¹¹Taizhou Hospital of Zhejiang Province, Taizhou, China,¹²Yunnan Cancer Hospital, Kunming, China,¹³Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China,¹⁴Sir Run Run Shaw Hospital, Hangzhou, China,¹⁵Jiangmen Central Hospital, Jiangmen, China,¹⁶Linyi Cancer Hospital, Linyi, China,¹⁷Chongqing University Cancer Hospital, Chongqing, China,¹⁸LaNova Medicines, Shanghai, China,¹⁹MSD China, Shanghai, China,²⁰Merck & Co., Inc., Rahway, NJ

摘要 Abstract

中文摘要

背景：MK-2010（LM-299）是一种新型PD-1×VEGF双特异性抗体。我们报告1/2期MK-2010-001/LM299-01-102研究（NCT06650566）的初步安全性和疗效。方法：在剂量递增队列中，晚期实体瘤参与者（pts）接受MK-2010 Q2W（0.3-30 mg/kg）或Q3W（0.3-40 mg/kg）。在NSCLC随机化队列（回填）中，PD-L1 TPS≥1%且无可干预基因突变的晚期NSCLC患者被随机分配至MK-2010 20 mg/kg或30 mg/kg Q3W。主要终点为剂量限制性毒性（DLT）、AE和严重AE。次要终点包括PK和由研究者评估的ORR（RECIST v1.1）。ORR在数据截止（2025年12月25日）前首次治疗≥6周的患者中进行评估。结果：112名患者接受治疗；剂量递增40名，NSCLC回填72名（20 mg/kg 35名，30 mg/kg 37名）。在回填中，68%的患者接受过既往治疗；60%接受过任何抗PD-(L)1治疗，26%接受过任何抗VEGF治疗。剂量递增队列的中位随访时间为7.9个月（0-14.4），回填为3.3个月（范围0.6-5.5）；中位治疗持续时间分别为2.6个月（范围0.03-9.8）和2.1个月（范围0.03-4.5）。总体发生两例DLT（剂量递增队列3 mg/kg Q3W时1例3级咯血，30 mg/kg回填时1例3级蛋白尿）。治疗中出现的AE发生率在剂量递增队列为95%，20 mg/kg回填为94%，30 mg/kg回填为92%；≥3级AE分别为53%、23%和49%，严重AE分别为30%、14%和32%。治疗相关AE（TRAE）在剂量递增队列为95%，20 mg/kg回填为80%，30 mg/kg回填为89%；≥3级TRAE分别为40%、17%和27%，严重TRAE分别为20%、6%和8%。未报告5级TRAE。一例TRAE导致停药（剂量递增队列3 mg/kg Q3W时）。VEGF类相关AE在20 mg/kg时发生于51%的患者，在30 mg/kg时为49%；≥3级VEGF类相关AE包括高血压（分别为9%和8%）、出血事件（0%和5%）和蛋白尿（0%和5%）。在剂量递增队列中，≥10 mg/kg Q3W患者中24%（4/17）、≥10 mg/kg Q2W患者中22%（2/9）观察到未确认缓解。20 mg/kg和30 mg/kg回填组患者的未确认ORR（n/N；95% CI）总体分别为30%（10/33；16-49）和28%（9/32；14-47），1L情况下为55%（6/11；23-83）和44%（4/9；14-79），2L+情况下为18%（4/22；5-40）和22%（5/23；7-44）。MK-2010稳态下的平均估计半衰期约为9天。结论：MK-2010在所测试的各剂量水平上表现出可控的安全性和有前景的抗肿瘤活性，包括在初治和IO难治性NSCLC中。入组正在进行，以进一步阐明MK-2010的安全性和疗效。

查看英文原文 English abstract

Background: MK-2010 (LM-299) is a novel PD-1×VEGF bispecific antibody. We report initial safety and efficacy from the phase 1/2 MK-2010-001/LM299-01-102 study (NCT06650566). Methods: In the dose escalation cohort, participants (pts) with advanced solid tumors received MK-2010 Q2W (0.3-30 mg/kg) or Q3W (0.3-40 mg/kg). In the NSCLC randomization cohort (backfill), pts with advanced NSCLC with PD-L1 TPS ≥1% and no actionable genetic mutations were randomized to MK-2010 20 mg/kg or 30 mg/kg Q3W. Primary endpoints were dose-limiting toxicities (DLTs), AEs, and serious AEs. Secondary endpoints included PK and ORR per RECIST v1.1 by investigator review. ORR was assessed in pts first treated ≥6 wk before data cutoff (Dec 25, 2025). Results: 112 pts were treated; 40 pts in dose escalation and 72 pts in the NSCLC backfill (35 at 20 mg/kg and 37 at 30 mg/kg). In the backfill, 68% of pts received prior therapy; 60% with any anti-PD-(L)1 and 26% with any anti-VEGF therapy. Median follow-up was 7.9 mo (0-14.4) for the dose escalation cohort and 3.3 mo (range 0.6-5.5) for the backfill; median duration of therapy was 2.6 mo (range 0.03-9.8) and 2.1 mo (range 0.03-4.5), respectively. Two DLTs occurred overall (gr 3 hemoptysis in the dose escalation cohort at 3 mg/kg Q3W and gr 3 proteinuria in the 30 mg/kg backfill). Treatment-emergent AEs occurred in 95% of pts in the dose escalation cohort, 94% in the 20 mg/kg backfill, and 92% in the 30 mg/kg backfill; AEs were gr ≥3 in 53%, 23%, and 49%, respectively, and serious in 30%, 14%, and 32%, respectively. Treatment-related AEs (TRAEs) occurred in 95% of pts in the dose escalation cohort, 80% in the 20 mg/kg backfill, and 89% in the 30 mg/kg backfill; TRAEs were gr ≥3 in 40%, 17%, and 27%, respectively, and serious in 20%, 6%, and 8%, respectively. No grade 5 TRAEs were reported. One TRAE led to discontinuation (in the dose escalation cohort at 3 mg/kg Q3W). VEGF class-related AEs occurred in 51% of pts at 20 mg/kg and 49% at 30 mg/kg; gr ≥3 VEGF class-related AEs included hypertension (9% and 8%, respectively), bleeding events (0% and 5%), and proteinuria (0% and 5%). In the dose escalation cohort, unconfirmed responses were seen in 24% (4/17) of pts at ≥10 mg/kg Q3W and 22% (2/9) at ≥10 mg/kg Q2W. Unconfirmed ORR (n/N; 95% CI) for pts in the 20 mg/kg and the 30 mg/kg backfill arms was 30% (10/33; 16-49) and 28% (9/32; 14-47) overall, 55% (6/11; 23-83) and 44% (4/9; 14-79) in the 1L setting, and 18% (4/22; 5-40) and 22% (5/23; 7-44) in the 2L+ setting. The mean estimated half-life for MK-2010 at steady state was ~9 days. Conclusions: MK-2010 showed manageable safety across the tested dose levels and promising anti-tumor activity, including in both treatment-naïve and IO-refractory NSCLC. Enrollment is ongoing to further characterize the safety and efficacy of MK-2010.

利益披露 Disclosure

J. Li, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ). LaNova Medicines, Shanghai, China ). W. Kou, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ). LaNova Medicines, Shanghai, China ). L. Sun, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ). LaNova Medicines, Shanghai, China ). Y. Zhao, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ). LaNova Medicines, Shanghai, China ). R. Zhao, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ). LaNova Medicines, Shanghai, China ). B. Wang, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ). LaNova Medicines, Shanghai, China ). S. Zhou, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ). LaNova Medicines, Shanghai, China ). J. Li, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ). LaNova Medicines, Shanghai, China ). X. Liu, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ). LaNova Medicines, Shanghai, China ). J. Zhao, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ). LaNova Medicines, Shanghai, China ). D. Lv, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ). LaNova Medicines, Shanghai, China ). G. Li, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ). LaNova Medicines, Shanghai, China ). J. Xue, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ). LaNova Medicines, Shanghai, China ). Y. Fang, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ). LaNova Medicines, Shanghai, China ). D. Lin, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ). LaNova Medicines, Shanghai, China ). J. Shi, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ). LaNova Medicines, Shanghai, China ). Y. Gong, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ). LaNova Medicines, Shanghai, China ). X. Qin, LaNova Medicines, Shanghai, China Employment. Y. Zuo, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA Employment, Stock Option. E. H. Knelson, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA Employment, Stock Option. W. Zhang, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA Employment, Stock Option. C. Zhou, Lily ). Sanofi ). BI ). LaNova Medicines, Shanghai, China ). Roche ). Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ). Qilu ). Hengrui ). Innovent Biologics ). C-Stone ). LUYE Pharma ). Top Alliance Biosciences ). Amoy Diagnostics ).

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