Preliminary results from the first-in-human study of MK-2010, a PD-1×VEGF bispecific antibody
Presenter: Jennifer Pawlowski Session: First-in-Human Phase I Clinical Trials Time: 4/20/2026 9:00:00 AM → 4/20/2026 12:00:00 PM
Authors
Jin Li 1 , Weizheng Kou 2 , Longhua Sun 3 , Yanqiu Zhao 4 , Rusen Zhao 5 , Baozhong Wang 6 , Shaozhang Zhou 7 , Juan Li 8 , Xuewen Liu 9 , Jun Zhao 10 , Dongqing Lv 11 , Gaofeng Li 12 , Junli Xue 13 , Yong Fang 14 , Daren Lin 15 , Jianhua Shi 16 , Yi Gong 17 , Xia Qin 18 , Yi Zuo 19 , Erik H. Knelson 20 , Weijuan Zhang 19 , Caicun Zhou 13 1 Shanghai GoBroad Cancer Hospital, China Pharmaceutical University, Shanghai, China, 2 The First Affiliated Hospital of Xinxiang Medical University, Xixiang, China, 3 The First Affiliated Hospital of Nanchang University, Nanchang, China, 4 The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China, 5 Zibo Municipal Hospital, Zibo, Shandong, China, 6 Liaocheng People’s Hospital, Liaocheng, China, 7 Guangxi Medical University Cancer Hospital, Nanning, China, 8 Sichuan Cancer Hospital, Sichuan, China, 9 The Third Xiangya Hospital of Central South University, Changsha, China, 10 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department I of Thoracic Oncology, Peking University Cancer Hospital and Institute, Beijing, China, 11 Taizhou Hospital of Zhejiang Province, Taizhou, China, 12 Yunnan Cancer Hospital, Kunming, China, 13 Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China, 14 Sir Run Run Shaw Hospital, Hangzhou, China, 15 Jiangmen Central Hospital, Jiangmen, China, 16 Linyi Cancer Hospital, Linyi, China, 17 Chongqing University Cancer Hospital, Chongqing, China, 18 LaNova Medicines, Shanghai, China, 19 MSD China, Shanghai, China, 20 Merck & Co., Inc., Rahway, NJ
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.
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 ).
Cited in
Control: 10332 · Presentation Id: 12075 · Meeting 21436