Abstract CT057: Preliminary results from the first-in-human study of MK-2010, a PD-1×VEGF bispecific antibody

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. Citation Format: Jin Li, Weizheng Kou, Longhua Sun, Yanqiu Zhao, Rusen Zhao, Baozhong Wang, Shaozhang Zhou, Juan Li, Xuewen Liu, Jun Zhao, Dongqing Lv, Gaofeng Li, Junli Xue, Yong Fang, Daren Lin, Jianhua Shi, Yi Gong, Xia Qin, Yi Zuo, Erik H. Knelson, Weijuan Zhang, Caicun Zhou. Preliminary results from the first-in-human study of MK-2010, a PD-1×VEGF bispecific antibody [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT057.