NG-350A Evaluated in FORTRESS Trial for Locally Advanced Rectal Cancer

The FORTRESS trial is evaluating NG-350A, an investigative immunotherapy, in patients with locally advanced rectal cancer to improve treatment outcomes.

The first patient with locally advanced rectal cancer has been enrolled onto the phase 1b proof-of-concept FORTRESS study which is evaluating the investigative immunotherapy NG-350A, according to data shared in a news release from Akamis Bio.

NG-350A will be combined with standard-of-care chemoradiotherapy in the proof-of-concept FORTRESS trial for adult patients with locally advanced rectal cancer and at least one risk factor for local or distant recurrence.

“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,” Dr. Oliver Rosen, Akamis Bio’s chief medical officer, said in the news release. “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 locally advanced rectal cancer in order to advance a new therapeutic approach that can improve the current standard of care for patients living with this disease.”

The investigative agent is a next generation, systemically administered immunotherapy designed to help the immune system fight cancer. This is done by driving intertumoral expression of a special type of antibody (CD40 agonist) into both the primary and metastatic tumor sites (where the tumor has spread).

Moreover, the clinical-stage, intravenously delivered T-SIGn therapeutic is designed to trigger the activation of antigen-presenting cells resident in solid tumors and their draining lymph nodes. In turn, this triggers both antigen-presenting cells (a type of immune cell) and T cells (another type of immune cell) to attack and destroy the cancer cells.

The safety tolerability and preliminary efficacy of NG-350A has been evaluated in the FORTITUDE study where the agent was given as an immunotherapy for patients with metastatic or advanced epithelial tumors. In the study, the agent demonstrated a consistent safety and tolerability profile, and according to the release, also provided strong evidence of tumor-selective delivery, replication and transgene expression.

More Information on the FORTRESS Trial

Colorectal cancer is the third most frequently diagnosed cancer in both men and women in the United States, with approximately 145,000 new cases each year. Within this group, around 45,000 individuals are diagnosed with rectal cancer, and nearly 60% of these cases are classified as locally advanced rectal cancer. Locally advanced rectal cancer occurs when rectal cancer spreads to nearby tissues or lymph nodes. In patients with this disease, tumors may extend through the muscle layers into the outermost parts of the rectum or, in more advanced cases, penetrate the rectal wall, potentially attaching to surrounding organs or structures and spreading to nearby lymph nodes.

FORTRESS is a multi-center, open-label, non-randomized designed to evaluate clinical complete response rates in patients with locally advanced rectal cancer. This study builds on previous research from the CEDAR study, which showed that patients with locally advanced rectal cancer had a significantly higher rate of complete response when treated with a combination of NG-350A and standard chemoradiotherapy versus chemoradiotherapy alone.

The trial aims to enroll approximately 30 adult patients aged 18 years or older with rectal cancer that has been confirmed through lab testing and is locally advanced. During the 12-week treatment period, participants will receive NG-350A plus CRT chemoradiotherapy, which includes oral capecitabine (a chemotherapy drug) and targeted radiation therapy. 

The primary end point of the study is to determine how many patients achieve a clinical complete response (no visible signs of cancer) by week 12. Key secondary end point measures include the incidence and severity of side effects, clinical response outcome and MRI-based tumor regression grade.

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