On January 27, 2025 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, reported updated clinical data from ADG126 in microsatellite stable colorectal cancer (MSS CRC) at the ASCO (Free ASCO Whitepaper) Gastrointestinal (GI) Cancers Symposium in San Francisco, CA (Press release, Adagene, JAN 27, 2025, View Source [SID1234649878]).
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"These data, from the loading dose expansion cohort of our Phase 1b/2 trial, continue to demonstrate ADG126’s potential for patients with colorectal cancer. Seeing four confirmed partial responses out of twelve patients, with no treatment related discontinuations, also highlights the differentiated therapeutic index of ADG126. CTLA-4 is clinically validated with a known correlation between dose, efficacy and toxicity to improve outcomes with PD-1 inhibitors, and now we know that our SAFEbody can deliver benefit to patients in a safe and efficacious way," said Peter Luo, Chairman, CEO & President of R&D at Adagene.
Dr. Marwan Fakih, Professor of Medical Oncology and Therapeutics Research at City of Hope added, "Masking technology, which leads to increased intra-tumoral accumulation of cleaved ADG126 and maintains an optimal plasma concentration following higher and repeat dosing of ADG126, as well as enhanced Treg depletion through binding to a novel epitope without Fc engineering, position ADG126 to be a best-in-class CTLA-4 inhibitor."
This Phase 1b/2, open-label, multicenter dose escalation and expansion combination study of ADG126 in combination with Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA (pembrolizumab; 200 mg, Q3W) in MSS CRC with no liver and peritoneum metastases previously demonstrated efficacy at the 10 mg/kgQ3W dose, with overall response rate (ORR) of 23%, including four confirmed partial responses and one unconfirmed partial response. Newly shared data with the 20 mg/kg loading dose followed by 10 mg/kg Q3W in combination with pembrolizumab achieved an improved ORR of 33%, and all responders remain on treatment at a maintenance dose of 10 mg/kg Q3W or 10 mg/kg Q6W in combination with pembrolizumab. Per protocol, dose modifications were permitted to manage toxicity, enabling investigators to optimize each patient’s course of treatment to further improve the duration of responses. Time to event endpoints will be reported when the data mature in 2025. Due to the enhanced therapeutic index of ADG126 in combination with anti-PD-1, the Company plans to evaluate a broader patient population in the dose expansion cohort, including patients with liver metastases, with standard of care combinations.
No Grade 4/5 safety events were seen with ADG126 to date and pruritus (25%) was the most commonly observed treatment-related adverse event (TRAE). Higher G2/G3 TRAEs were observed in the loading dose cohort but were managed through dose modification and infrequent use of infliximab/medical intervention, resulting in no discontinuations to date. The totality of data to date supports that Adagene’s anti-CTLA-4, ADG126, plus pembrolizumab has potential to be a best-in-class treatment for patients with MSS CRC.