China-based Adagene Inc. (NASDAQ: ADAG) has announced interim results from its combination dose escalation studies of the masked, anti-CTLA-4 SAFEbody, ADG126, at the AACR Annual Meeting in Orlando, Florida, from April 14-19, 2023. The studies include a Phase Ib/II study for ADG126 as a monotherapy and in combination with toripalimab (an anti-PD-1 antibody) in patients with advanced/metastatic solid tumors, as well as a Phase Ib/II study for ADG126 in combination with pembrolizumab (an anti-PD-1 antibody) in similar patient populations.
Safety Profile and Tolerability of ADG126
In dose escalation studies of ADG126 in combination with anti-PD-1 treatments, ADG126 continues to demonstrate a best-in-class safety profile at doses from 6 mg/kg up to 10 mg/kg. The combination was well tolerated with no dose-limiting toxicities observed with repeat cycles, including in patients who received four or more cycles in the combination cohort with toripalimab. In heavily pre-treated patient groups, clinical responses and tumor shrinkage were observed during combination dose escalation.
Clinical Benefits and Tumor Shrinkage
The posters summarize patient case studies demonstrating clinical benefit, including three confirmed partial responses and multiple cases of prolonged stable disease with tumor shrinkage in patients who received ADG126 plus anti-PD-1 therapies. Notably, two cases of significant tumor shrinkage (20% reduction and higher in target lesions) were observed in MSS CRC patients with liver metastasis who received ADG126 plus toripalimab.
Monotherapy and Mechanism of Action
An additional cohort of 30 patients who received ADG126 monotherapy showed a compelling safety profile for ADG126, with no Grade 3 or higher TRAEs reported at repeat doses up to 20 mg/kg. Across all dose levels, the disease control rate was 37% among 27 evaluable patients. Analysis of a clinical sample from a hepatocellular carcinoma (HCC) patient previously treated with atezolizumab and bevacizumab demonstrated Treg depletion, supporting the mechanism of action for ADG126.
Ongoing Studies and Collaborations
Dose expansion cohorts are currently underway evaluating ADG126 in combination with anti-PD-1 therapy, with an update planned for later in 2023. Furthermore, the strong safety profile of ADG126 has enabled a randomized clinical trial in collaboration with Roche to evaluate ADG126 in combination with atezolizumab and bevacizumab as a first-line treatment for patients with advanced/metastatic HCC.-Fineline Info & Tech
