Adagene Presents ESMO Results on ADG126 with KEYTRUDA in Advanced MSS Colorectal Cancer

Adagene Inc., a biotechnology firm listed on Nasdaq under the ticker ADAG, has unveiled promising new clinical data for its innovative antibody-based therapy, ADG126. This data was presented at the ESMO Congress held in Barcelona, Spain, from September 13-17, 2024. The findings are from an ongoing phase 1b/2 trial, investigating ADG126, a masked anti-CTLA-4 SAFEbody, used in combination with pembrolizumab, an anti-PD-1 therapy developed by Merck & Co.

Dr. Daneng Li, Associate Professor at the City of Hope Comprehensive Cancer Center, praised the results, highlighting the encouraging safety and efficacy profiles of ADG126 when administered at higher doses than currently available anti-CTLA-4 therapies. Dr. Li noted that the combination of ADG126 and pembrolizumab could potentially benefit a broader range of patients, including those with liver metastases, particularly when used alongside standard care treatments to manage early disease progression.

ADG126 targets a unique epitope of CTLA-4 on regulatory T cells (Tregs) within tumor tissues, showing a promising safety and efficacy profile when combined with pembrolizumab. This SAFEbody technology is designed to minimize on-target off-tumor toxicity, enhancing its overall therapeutic index. The treatment has shown minimal immunogenicity and anti-drug antibodies, with no significant impact on its pharmacokinetic profile.

In the clinical trial involving 66 heavily pre-treated patients with advanced/metastatic solid tumors, ADG126 demonstrated a differentiated safety profile. No dose-limiting toxicities or severe treatment-related adverse events (TRAEs) were observed at doses up to 20 mg/kg, evaluated during the dose escalation phase. Notably, the therapy did not induce Grade 3 colitis, a common side effect of similar treatments, and required limited use of infliximab to manage immune-mediated diarrhea or colitis in less than 10% of patients. The discontinuation rate due to side effects was also low, at 8%.

Efficacy data were equally promising. Among the efficacy-evaluable patients without liver and peritoneal metastases (n=17) who received the 10 mg/kg dose every three weeks, the overall response rate (ORR) was 24%, with four confirmed partial responses. These figures are significantly higher than the 1% to 6.3% ORR typically observed with current standard care treatments. The overall disease control rate (DCR) was 88%, with 11 patients maintaining stable disease. Additionally, the median progression-free survival (PFS) was 8.5 months at the 10 mg/kg dose, and the 12-month overall survival (OS) rates were 74% for patients without liver metastases and 82% for those without liver and peritoneal metastases.

Based on these findings, a 20 mg/kg loading dose followed by 10 mg/kg maintenance doses is being evaluated in an expanded cohort, with initial data expected later this year. Comprehensive pharmacokinetic and exposure-response analyses have reinforced the therapeutic potential of ADG126, guiding future dose selections to meet regulatory requirements.

Peter Luo, CEO and President of R&D at Adagene, expressed enthusiasm over the results, indicating that the findings validate the clinical benefits of ADG126, especially at higher doses. He emphasized that these results provide a strong foundation for advancing ADG126 in a randomized, registration-oriented clinical program, potentially transforming the treatment landscape for patients with metastatic MSS CRC.

Overall, Adagene's innovative approach using its SAFEbody precision masking technology continues to show significant promise in improving patient outcomes, reducing treatment-related toxicity, and offering new therapeutic options for challenging cancer types.