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

NG-350A, an intravenously delivered oncolytic immunotherapy, has been granted fast track designation by the FDA for the treatment of mismatch repair-proficient (pMMR) locally advanced rectal cancer (LARC).¹

NG-350A is a next-generation, blood-stable adenoviral T-SIGn vector that expresses a potent IgG agonistic anti-CD40 antibody. As a tumor-selective agent, it is engineered to selectively deliver the anti-CD40 antibody to multiple tumors while avoiding systemic toxicity, generating an antitumor response.

The FDA grants fast track designation to drugs that address unmet medical needs in serious conditions, with an ultimate goal of bringing the agent to patients earlier.² Encouraging early clinical data have positioned NG-350A as a potential therapeutic that could meet the need of improving standard of care for pMMR tumors, present in a vast majority of LARC patients.² With this designation, Akamis Bio, the sponsor, is eligible for more interactions with the FDA on drug development plans and clinical trial design, as well as accelerated approval and priority review if criteria are met.

“The NG-350A [f]ast [t]rack designation from FDA is a recognition of the significant unmet need for new therapies to treat [LARC],” said Oliver Rosen, MD, chief medical officer of Akamis Bio, in a press 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.”

What Is NG-350A’s Current Stage of Development?

NG-350A is being evaluated in the ongoing, actively recruiting phase 1b FORTRESS trial (NCT06459869) in adult patients with histologically confirmed, locally advanced adenocarcinoma of the rectum from clinical stages I to III.⁴ Initiated in April 2025, the study is a multicenter, open-label, nonrandomized trial that aims to enroll 30 patients. The single investigational arm is receiving intravenous NG-350A in combination with chemoradiotherapy for a 12-week study treatment period, during which investigators are monitoring patients for clinical complete response (cCR) by the end of the period. Secondary outcome measures include incidence and severity of adverse events, clinical response, and MRI-based tumor regression.

NG-350A demonstrated a consistent safety and tolerability profile in prior studies.⁵ Before the FORTRESS trial, the first-in-human, nonrandomized phase 1a FORTITUDE trial (NCT03852511) assessed the safety, tolerability, preliminary efficacy, and pharmacokinetics of NG-350A as monotherapy and in combination with the checkpoint inhibitor pembrolizumab (Keytruda) in patients with advanced or metastatic epithelial tumors.⁶ Eligible tumors included urothelial carcinoma, head and neck squamous cell carcinoma, microsatellite instability (MSI)-high/MMR-deficient cancer, non–small cell lung cancer, uterine/endometrial cancer, cervical cancer, esophageal cancer, gastric cancer, cutaneous squamous cell carcinoma, hepatocellular carcinoma, and triple-negative breast cancer. The results of this study were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the Journal for ImmunoTherapy of Cancer.

In addition, the phase 1a/1b FORTIFY study (NCT05165433) is continuing dose escalation of the agent in combination with pembrolizumab, also in patients with advanced or metastatic epithelial tumors.⁷

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 14, 2025. https://tinyurl.com/ns3unmd8

2. Fast Track. US Food & Drug Administration. Updated August 13, 2024. Accessed October 15, 2025. https://tinyurl.com/ms2695jn

3. Rosen LS, Camidge DR, Khalil D, et al. FORTITUDE: Results of a phase 1a study of the novel transgene-armed and tumor-selective vector NG-350A with and without pembrolizumab (pembro). J Clin Oncol. 2022;40(16_suppl):2559-2559. doi:10.1200/jco.2022.40.16_suppl.2559

4. NG-350A Plus Chemoradiotherapy for Locally Advanced Rectal Cancer (FORTRESS). ClinicalTrials.gov. Updated August 11, 2023. Accessed October 15, 2025. https://clinicaltrials.gov/study/NCT06459869

5. Naing A, Khalil D, Rosen O, et al. First-in-human clinical outcomes with NG-350A, an anti-CD40 expressing tumor-selective vector designed to remodel immunosuppressive tumor microenvironments. JITC. 2024;12(10):e010016-e010016. doi:10.1136/jitc-2024-010016

6. 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://clinicaltrials.gov/study/NCT03852511

7. Study of NG-350A Plus Pembrolizumab in Metastatic or Advanced Epithelial Tumours (FORTIFY). ClinicalTrials.gov. Updated August 11, 2025. Accessed October 15, 2025. https://clinicaltrials.gov/study/NCT05165433