Adagene's Muzastotug Receives FDA Fast Track Designation for MSS Colorectal Cancer
Key Insights
The FDA has granted Fast Track designation to muzastotug (ADG126) in combination with pembrolizumab for treating adult patients with microsatellite stable metastatic colorectal cancer (search) without liver metastases.
Muzastotug is a next-generation masked anti-CTLA-4 (search) SAFEbody engineered to overcome CTLA-4-mediated Treg resistance with enhanced safety and efficacy compared to existing CTLA-4 therapies.
The designation is supported by emerging clinical evidence showing encouraging efficacy, deep and durable responses, and a favorable safety profile in heavily pretreated patients.
Adagene Inc. announced that the U.S. Food and Drug Administration has designated muzastotug (ADG126), in combination with Merck (search)'s anti-PD-1 (search) therapy KEYTRUDA (pembrolizumab), as a Fast Track product for adult patients with microsatellite stable metastatic colorectal cancer (search) (MSS mCRC (search)) without current or active liver metastases. The designation underscores the potential of SAFEbody-enabled anti-CTLA-4 (search) therapy to address unmet medical needs in this challenging patient population.
Novel Masking Technology Shows Promise
Muzastotug is a next-generation masked anti-CTLA-4 (search) SAFEbody engineered to overcome CTLA-4-mediated Treg resistance in tumors with enhanced safety and efficacy, delivering a therapeutic index beyond the reach of existing CTLA-4 therapies. The drug uses Adagene's proprietary masking technology to preferentially activate antibody binding within the tumor microenvironment, thereby reducing systemic toxicity while maintaining antitumor potency.
The Fast Track Designation is supported by emerging clinical evidence demonstrating encouraging efficacy, deep and durable responses, and a favorable safety profile of muzastotug across a heavily pretreated patient population. Fast Track is designed to facilitate drug development and expedite the review of therapies intended to treat serious conditions with unmet medical need.
"Receiving Fast Track Designation marks an important milestone for Adagene and further validates the promise of our SAFEbody technology to unlock CTLA-4 (search) biology in a fundamentally safer and more effective way," said Peter Luo, Ph.D., Chief Executive Officer and President of R&D at Adagene. "We are deeply encouraged by the responses we are seeing with muzastotug in combination with pembrolizumab and believe this therapy has the potential to reshape the treatment paradigm by offering patients an opportunity for extended survival with an improved quality of life."
Clinical Development Pathway Confirmed
The Fast Track Designation enables more frequent FDA interactions and may allow for rolling review of future marketing applications as Adagene continues the ongoing randomized Phase 2 and prepares for the registration trial, planned to begin in 2027.
Both the randomized Phase 2 and Phase 3 trial designs and endpoints were confirmed following a meeting with the FDA. Future trials will enroll late-line patients with MSS CRC without liver metastases, including those with peritoneal metastasis/involvement.
Phase 2 Trial Design
The Phase 2 dose optimization cohort will randomize patients to either 10 mg/kg or 20 mg/kg of muzastotug in combination with pembrolizumab, using an induction-maintenance regimen, without cycle limitations of muzastotug. Up to 30 patients will be enrolled in each arm of the Phase 2 study, without a requirement for a muzastotug monotherapy arm.
The primary endpoint of the Phase 2 trial will be overall response rate (ORR). Secondary endpoints include duration of response (DOR), progression-free survival (PFS), and overall survival (OS).
Phase 3 Trial Framework
The FDA agreed with Adagene's proposed standard-of-care (SOC) control arm for the Phase 3 clinical trial and confirmed that a muzastotug monotherapy arm was also not required. The primary endpoint of the Phase 3 trial will be OS, with secondary endpoints including PFS, DOR and ORR.
SAFEbody Platform Technology
Adagene's SAFEbody technology is designed to address safety and tolerability challenges associated with many antibody therapeutics by using precision masking technology to shield the binding domain of the biologic therapy. Through activation in the tumor microenvironment, this allows for tumor-specific targeting of antibodies, while minimizing on-target off-tumor toxicity in healthy tissues.
ADG126 (muzastotug) is a masked, anti-CTLA-4 (search) SAFEbody that targets a unique epitope of CTLA-4 in regulatory T cells (Tregs) in the tumor microenvironment. The drug is currently in Phase 1b/2 and Phase 2 clinical studies in combination with anti-PD-1 (search) therapy, particularly focused on metastatic microsatellite-stable (MSS) colorectal cancer (search).
Luo indicated that the company looks forward to sharing updated topline Phase 1b/2 clinical data over the next few months as they continue advancing this program with urgency and purpose.