On April 3, 2025 Akamis Bio, a clinical-stage oncology company using a proprietary Tumor-Specific Immuno-Gene Therapy (T-SIGn) platform to deliver novel immunotherapeutic payloads to solid tumors, reported enrollment of the first patient in the proof-of-concept FORTRESS study of NG-350A in locally advanced rectal cancer (LARC) (Press release, Akamis Bio, APR 3, 2025, View Source [SID1234651800]).
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FORTRESS is a multi-center, open-label, non-randomized, Phase 1b study designed to measure clinical complete response (cCR) rates in patients with LARC. The study builds upon the Akamis Bio-supported, CEDAR study, which showed a significantly greater complete response rate in LARC patients treated with a combination of Akamis Bio’s first generation immunotherapy and chemoradiotherapy (CRT), relative to expected outcomes using standard-of-care CRT alone. Prior clinical studies of NG-350A have demonstrated a favorable safety profile for the therapy, with no observed transgene-related or off-target toxicities.
"We have previously demonstrated that intravenously administered T-SIGn therapeutics can reach both primary and metastatic tumor sites to drive local expression of immunotherapeutic payloads," said Oliver Rosen, MD, Akamis Bio’s chief medical officer. "The results from prior clinical studies have provided what we believe is a clear roadmap for the design of the FORTRESS trial, where our aim is to demonstrate the safety and efficacy of NG-350A in LARC in order to advance a new therapeutic approach that can improve the current standard of care for patients living with this disease."
About the FORTRESS Trial
The Phase 1b FORTRESS trial (NCT06459869) is an open-label, single-arm, and multicenter trial of NG-350A in combination with chemoradiotherapy (CRT) in adult patients with locally advanced rectal cancer (LARC) and at least one risk factor for local or distant recurrence or with oligometastatic disease. The study is planning to enroll approximately 30 patients aged eighteen and older with histologically confirmed adenocarcinoma of the rectum which is locally advanced (clinical stage II-III based on pelvic MRI). During the 12-week active study treatment period, patients will receive NG-350A plus CRT (oral capecitabine plus long-course intensity-modulated radiotherapy). The primary endpoint for the study will be the proportion of patients achieving a clinical complete response (cCR) at week 12. Key secondary endpoints will include the incidence and severity of adverse events, clinical response (CR) outcome, and MRI-based tumor regression grade (mrTRG).
About NG-350A
NG-350A is a clinical-stage, intravenously delivered T-SIGn therapeutic designed to drive intratumoral expression of a CD40 agonist monoclonal antibody triggering the activation of antigen-presenting cells (APCs) resident in solid tumors and their draining lymph nodes. Once activated, APCs recruit T cells into the vicinity of the tumor to deliver a potent anti-tumor immune response. Akamis Bio has evaluated NG-350A’s safety, tolerability, and preliminary efficacy as a monotherapy (FORTITUDE study) and in combination with pembrolizumab (FORTIFY study) in patients with metastatic or advanced epithelial tumors. Across these studies, NG-350A has demonstrated a consistent safety and tolerability profile, as well as strong evidence of tumor-selective delivery, replication and transgene expression.
About LARC
Colorectal cancer is the third most common cancer diagnosed in both men and women in the United States with about 145,000 people newly diagnosed each year. Amongst the incident colorectal cancer population, about 45,000 people are diagnosed specifically with rectal cancer of which approximately 60 percent have locally advanced rectal cancer (LARC). LARC is defined by the spread of the rectal cancer to nearby tissues or lymph nodes. In patients with LARC, tumors have either grown through muscle and into the outermost layers of the rectum, or in more severe cases, through the wall of the rectum where they may attach to other organs or structures and/or into the lymph nodes.
About T-SIGn
Akamis Bio’s T-SIGn therapeutics are based on a replication competent, chimeric group B adenovirus backbone which has been adapted via directed evolution to home specifically to both primary and metastatic epithelial-derived solid tumor tissue following intravenous delivery. Once at the tumor site, T-SIGn therapeutics can drive the intratumoral expression of multiple transgene payloads, turning solid tumor cells into "drug factories" while leaving healthy tissue unaltered and intact. The intratumoral expression of immunologically active biomolecules and therapeutic proteins can result in the remodeling of the solid tumor microenvironment, triggering robust antitumor immune responses. T-SIGn therapeutics have the potential to be used in the monotherapy setting, as well as in combination with other immuno-oncology agents to target the key mechanisms that tumors use to evade the immune system.