2025 ASCO Data Presentation
May 2025
Safety and Efficacy of ADG126 (an Anti-CTLA-4 Masking Antibody) in Combination with Pembrolizumab:
Updated Results of Phase 1b/2 Study in Advanced MSS CRC
Daneng Li1*, Sun Young Kim2*, Manish R. Patel3, Hee Kyung Kim4, Sunil Sharma5, Sang Joon Shin6, Jeeyun Lee7, Sae Won Han8, George Lau9, Brigette Ma10, Yan Li11, Songmao Zheng11, Luke Chung11, Ping Xiao11, Kristine She11, Qinghai Zhao11, Dana Hu-Lowe11, Stanley Frankel11, Michael J. Chisamore12, Peter Luo11, Jiping Zha11, Marwan Fakih1
.
1. City of Hope Comprehensive Cancer Center, Los Angeles, USA; 2. Asan Medical Center, University of Ulsan College of Medicine, Republic of Korea; 3. Florida Cancer Specialists/Sarah Cannon Research Institute, USA. 4. Chungbuk National University Hospital, Republic of Korea; 5. Honor Health Research Institute, USA; 6. Yonsei Cancer Center C University Health System, Republic of Korea; 7. Samsung Medical Center, Republic of Korea; 8. Seoul National University Hospital, Republic of Korea; 9. Humanity C Health Medical Group Ltd, Hong Kong SAR, China; 10. The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China; 11. Adagene Inc., USA; 12. Merck C Co., Inc., Rahway,
NJ, USA; . * These authors contributed equally
.
Introduction and Background
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Microsatellite Stable (MSS) CRC accounts for ~95% of all metastatic CRC and remains largely unresponsive to first-generation checkpoint inhibitors1. MSS CRC is characterized by an immunologically "cold" tumor microenvironment (TME), defined by high infiltration of CTLA-4+ regulatory T cells (Tregs), low levels of CD8+ T cells (TILs), and minimal or negative PD-L1 expression.
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ADG126 is a masked anti-CTLA-4 IgG1 SAFEbody with cleavable masking peptides engineered to be preferentially activated in the TME. It binds to a unique epitope to block CTLA-4 function, primes T cells and depletes Tregs through epitope-enhanced ADCC/P (Fig. 1).
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ADG126 can be dosed more than 6-fold higher in combination with anti-PD-1 antibodies with predicted tumor active drug exposures ≥ 10 to 20-fold higher than its unmasked parental antibody and with significantly reduced on-target/off-tumor toxicities2.
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This selective TME reprogramming of ADG126 promotes TILs and synergizes with anti-PD-1
therapies such as pembrolizumab (Pembro) to elicit anti-tumor activity.
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We have been conducting a Phase 1b/2 trial evaluating ADG126 + Pembro combination (NCT05405595) in late line MSS CRC3. Here we share the updated results of clinical efficacy and safety of the IO doublet across several dose levels/regimens guided by quantitative PK/PD modeling.
References: 1, San-Román-Gil et al., Cancers (Basel). 2023;15:863 and references within. 2, Zheng S. et al., Abstract#506, SITC Annual Meeting, 2024. 3. Daneng Li et al., 3
Abstract#129, ASCO GI Conference, 2025, and references within.
Introduction and Background (Conti'd)
Figure 1. Unique and Effective Mechanism of Action (MOA) of ADG126
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Methods and Study Design Schema
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This is a Phase 1b/2, open-label, multicenter dose escalation and expansion combination study of ADG126 + pembrolizumab (200 mg, Q3W) in advanced solid tumors. The study design schema for the dose escalation (DE) and dose expansion (EXP) MSS CRC cohorts is shown below:
Dose Escalation (ADG126 Dose Level) Dose Expansion (EXP) in MSS CRC*
20 mg/kg Q3W + P (N = 6)
20 mg/kg Q6W + P (N = 5)
10 mg/kg Q3W + P (N = 3)
10 mg/kg Q6W + P (N = 3)
6 mg/kg Q3W + P (N = 5)
20 mg/kg Q6W + P (N = 7; enrollment ongoing)
20 mg/kg LD + 10 mg/kg Q3W + P (N = 14)
10 mg/kg Q3W + P (N = 30)
10 mg/kg Q6W + P (N = 11)
*. P: pembrolizumab (200 mg, Q3W iv). *. All are without liver metastasis (NLM); LD: Loading Dose. 5
not listed: one patient at ADG126 (6 mg/kg Q6W) + Pembrolizumab.
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Adagene Inc. published this content on May 31, 2025, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on May 31, 2025 at 12:16 UTC.
