China-based biotech Adagene Inc. (NASDAQ: ADAG), which also operates out of San Diego, California, has announced data for its masked anti-CTLA-4 SAFEbody, ADG126, in combination with anti-PD-1 therapy in patients with advanced/metastatic solid tumors. The results, as of January 6, 2023, demonstrate the safety and initial efficacy profiles of ADG126 in combination with anti-PD-1 treatment. Adagene plans to present detailed dose escalation data at an upcoming medical conference in the first half of 2023.
Clinical Trial Results
Key findings include the administration of ADG126 at escalating doses up to 10 mg/kg every three weeks in combination with a fixed dose of anti-PD-1 therapy (toripalimab = 240 mg), including repeat dosing cycles. The combination was well tolerated, with no dose-limiting toxicities observed or maximum tolerated dose yet reached. As of January 6, 2023, an additional 10 patients are being evaluated with the combination of ADG126 and pembrolizumab in a separate clinical trial.
Expansion Cohorts and FDA Initiative
Following the completion of the dose escalation cohorts, two separate doses of ADG126 (6 mg/kg and 10 mg/kg evaluated every three or six weeks) are proceeding in expansion cohorts to address different tumor types. This follows the goal of the FDA’s ‘Project Optimus’ initiative to reform the dose optimization and dose selection paradigm in oncology drug development.
Therapeutic Observations
Adagene also confirmed several partial responses were observed in multiple tumor types during combination dose escalation. Continuous tumor shrinkage has been observed in cold tumors (e.g., MSS CRC) and immune-oncology-resistant patients with difficult-to-treat tumor types.
ADG126 Platform and Mechanism
Adagene’s ADG126 was designed on the firm’s SAFEbody platform, which aims to reduce on-target off-tumor toxicity that affects antibody therapeutics. The drug, with excellent performance in pre-clinical studies, is activated only under the condition of the tumor microenvironment (TME). It enhances the therapeutic effect by effectively clearing regulatory T cells (Treg) and maintains its physiological function by blocking with flexible ligands, significantly improving the therapeutic window and addressing safety issues of existing CTLA-4 therapies.
Future Outlook
The positive results from the clinical trials of ADG126 highlight Adagene’s commitment to advancing innovative cancer therapies. With demonstrated safety and efficacy in combination with anti-PD-1 therapy, ADG126 is poised to make a meaningful impact on patient outcomes in advanced solid tumors. Adagene’s ongoing research and development efforts underscore its dedication to improving the treatment landscape for patients with challenging cancers.-Fineline Info & Tech
