FDA Grants Fast Track Designation to NG-350A For pMMR Rectal Cancer

The FDA has granted fast track designation to NG-350A, an intravenously delivered T-SIGn® therapeutic, for the treatment of patients with mismatch repair-proficient (pMMR) locally advanced rectal cancer (LARC), according to a news release from the developer, Akamis Bio.¹

The oncolytic immunotherapy is currently being assessed with chemotherapy in the phase 1b FORTRESS trial (NCT06459869) among patients with pMMR LARC. Furthermore, the safety, tolerability, and preliminary efficacy of NG-350A as a monotherapy was assessed among patients with metastatic or advanced epithelial tumors in the phase 1a/1b FORTITUDE trial (NCT03852511) and in combination with pembrolizumab in the same population in the phase 1a/1b FORTIFY trial (NCT05165433).^2,3 In both studies, NG-350A exhibited a consistent safety and tolerability profile while showing strong evidence of tumor-selective delivery, replication, and transgene expression.

“The NG-350A fast track designation from the FDA is a recognition of the significant unmet need for new therapies to treat LARC,” Oliver Rosen, MD, chief medical officer at Akamis Bio, stated in the news release.¹ “The global incidence of LARC continues to rise, with a particularly alarming increase of this cancer among younger populations. Patients with [pMMR] 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.”

The open-label, single-arm study will enroll adult patients with pMMR LARC and at least 1 risk factor for local or distant recurrence or patients with oligometastatic disease. Those in the study will receive NG-350A intravenously, oral capecitabine, and long-course intensity-modulated radiotherapy during a 12-week active study treatment period. Developers seek to enroll approximately 30 patients who are 18 years and older in the FORTRESS study.

Preceding the FORTRESS study, the developers evaluated an oncolytic adenovirus, enadenotucirev (EnAd), among patients with LARC in the phase 1 CEDAR trial (NCT03916510).⁴ When given with chemoradiotherapy, the combination exhibited significantly higher responses per MRI-assessed tumor regression grade and pathological complete response (pCR) rates, both of which were 41.6%, vs the expected rates for standard chemoradiation alone, at around 20%. The combination also exhibited an acceptable safety profile and was well-tolerated in this patient population, establishing the feasibility of oncolytic immunotherapy with chemoradiation in those with LARC.

The primary end point of the FORTRESS trial is the proportion of patients achieving a clinical complete response at week 12. Secondary end points include incidence and severity of adverse effects, clinical response outcomes, and MRI-based tumor regression grade.

Developers engineered NG-350A to drive intratumoral expression of a CD40 agonist monoclonal antibody to trigger the activation of antigen-presenting cells (APCs). Following the activation of APCs, T cells are recruited to facilitate an anti-tumor response.

Patients included in the phase 1b FORTRESS trial have histological confirmation of rectal adenocarcinoma; confirmed microsatellite stable or pMMR status; an ECOG performance status of 0 or 1; and adequate lung, hepatic, bone marrow, and hematological function within 10 days of initial NG-350A dose.⁵

Exclusion criteria include evidence of recurrent rectal cancer, distant metastatic disease not amenable to radical treatment or chemoradiation, other active malignancy within 3 years of study treatment except for early-stage cancer definitively treated with curative intent, and prior splenectomy. Additionally, patients are deemed ineligible for enrollment if they have active autoimmune disease requiring systemic therapy within 2 years of study treatment, infectious or inflammatory bowel disease within 3 months of study treatment, and major surgery within 14 days of the first study dose.

References

1. Akamis Bio receives FDA fast track designation for NG-350A for the treatment of mismatch repair-proficient locally advanced rectal cancer. News release. Akamis Bio. October 14, 2025. Accessed October 15, 2025. https://tinyurl.com/mxjzhfnh
2. First in human study of NG-350A (an oncolytic adenoviral vector which expresses an anti-CD40 antibody) (FORTITUDE). ClinicalTrials.gov. Updated June 24, 2022. Accessed October 15, 2025. https://tinyurl.com/mr2vj3j8
3. Study of NG-350A plus pembrolizumab in metastatic or advanced epithelial tumours (FORTIFY) (FORTIFY). ClinicalTrials.gov. Updated August 11, 2025. Accessed October 15, 2025. https://tinyurl.com/rujync8m
4. Akamis Bio highlights data showing potential of its adenovirus vector technology in combination with radiation to treat advanced rectal cancer. News release. Akamis Bio. October 3, 2023. Accessed October 15, 2025. https://tinyurl.com/595xkmx5
5. NG-350A plus chemoradiotherapy for locally advanced rectal cancer (FORTRESS). ClinicalTrials.gov. Updated August 11, 2025. Accessed October 15, 2025. https://tinyurl.com/yc4avb7e