Adagene doses first subject in Phase II MSS colorectal cancer trial
Adagene has initiated its Phase II trial for ADG126, an anti-CTLA-4 therapy, in combination with Keytruda for treating microsatellite stable colorectal cancer (MSS CRC) without liver metastases. The trial aims to evaluate overall response rate as the primary endpoint, with secondary endpoints including overall survival, duration of response, and progression-free survival. The study will randomize participants to receive either 10mg/kg or 20mg/kg doses. The trial is expected to conclude in early 2027, following FDA alignment on endpoints and designs.
Adagene has dosed the first participant in its open label, randomised Phase II trial studying muzastotug (ADG126), along with MSD’s anti-PD-1 therapy Keytruda (pembrolizumab), for the treatment of microsatellite stable colorectal cancer (MSS CRC) without liver metastases.
ADG126, the company’s lead clinical programme, is an anti-Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) SAFEbody that targets a unique CTLA-4 epitope in regulatory T cells in the tumour microenvironment.
The trial’s primary goal is overall response rate (ORR). Secondary endpoints will encompass overall survival (OS), duration of response (DOR), and progression-free survival (PFS).
It is currently underway and will support a clear path to Phase III study based on an earlier alignment with the US Food and Drug Administration (FDA).
In the Phase II dose optimisation cohort, the trial subjects will be randomised to either 10mg/kg or 20mg/kg of muzastotug and Keytruda with up to 30 participants per cohort.
The study is anticipated to conclude in early 2027.
Adagene R&D CEO and president Peter Luo said: “To date, muzastotug has been safely dosed at 20mg/kg Q6W, with less than 20% Grade 3 adverse events and no discontinuations, supporting its position as the potential best in class Treg depleting anti-CTLA-4 agent with improved therapeutic window.”
In July 2025, Adagene received confirmation from the FDA regarding both Phase II and Phase III endpoints and designs.
Future studies will enrol late-line MSS CRC participants who do not have liver metastases, including individuals with peritoneal metastasis.
The FDA has also granted approval for Adagene’s proposal to include a standard-of-care (SOC) control arm for the Phase III study, confirming that a muzastotug monotherapy arm is unnecessary.
For the Phase III study, OS will serve as the primary endpoint, with additional secondary measures, including ORR, PFS and DOR.
