The U.S. FDA has granted Fast Track designation to NG-350A, a novel oncolytic immunotherapy, for the treatment of mismatch repair–proficient (pMMR) locally advanced rectal cancer (LARC) — a subtype representing about 90% of all rectal cancer cases and historically resistant to immune checkpoint inhibitors.
What is NG-350A
NG-350A is a next-generation adenoviral T-SIGn vector designed to express a potent agonistic anti-CD40 antibodydirectly within tumor tissue. By selectively delivering this immune-activating signal to cancer cells while minimizing systemic exposure, NG-350A aims to enhance antitumor immune activation and reduce systemic toxicity. CD40 stimulation has long been recognized as a powerful driver of dendritic cell activation and T-cell priming, but previous systemic CD40 agonists were limited by safety concerns. NG-350A’s tumor-selective design may overcome these challenges.
Fast Track Designation
The FDA’s Fast Track designation is intended to accelerate the development and review of new therapies that address unmet medical needs in serious conditions. For Akamis Bio, the sponsor of NG-350A, this designation enables closer regulatory collaboration, rolling review, and the potential for accelerated or priority approval if clinical data demonstrate meaningful benefit.
Dr. Oliver Rosen, Chief Medical Officer of Akamis Bio, emphasized the importance of this milestone:
“This Fast Track designation from the FDA is a recognition of the significant unmet need for new therapies to treat locally advanced rectal cancer.”
He further noted:
“The global incidence of LARC continues to rise, with a particularly alarming increase among younger populations. Patients with mismatch repair–proficient tumors account for approximately 90% of LARC cases, and this population has the greatest need for evolution in the standard of care to include treatments that may enable patients to avoid surgical interventions.”
Current Development: FORTRESS Trial
NG-350A is currently being evaluated in the ongoing Phase 1b FORTRESS trial (NCT06459869), launched in April 2025. This multicenter, open-label, nonrandomized study aims to enroll 30 patients with stage I–III rectal adenocarcinoma. Participants receive intravenous NG-350A combined with standard chemoradiotherapy over 12 weeks.
The primary objective is to assess the clinical complete response (cCR) rate by the end of treatment, with secondary endpoints including safety, adverse events, MRI-based tumor regression, and overall tolerability.
Earlier Clinical Experience
Prior studies have shown NG-350A to be well tolerated and biologically active. The Phase 1a FORTITUDE trial (NCT03852511) tested NG-350A alone and in combination with pembrolizumab across multiple epithelial tumor types, demonstrating a manageable safety profile and early signs of immune activation. A related Phase 1a/1b FORTIFY study (NCT05165433) is also exploring NG-350A plus pembrolizumab in advanced solid tumors.