Akamis Bio's NG-350A Shows 50% Response Rate in Locally Advanced Rectal Cancer Phase 1b Trial
Key Insights
Akamis Bio's NG-350A combined with chemoradiotherapy (search) achieved a 50% composite response rate in the first 10 patients with mismatch repair-proficient locally advanced rectal cancer (search), doubling the expected 25% rate from standard treatment alone.
The Phase 1b FORTRESS study demonstrated no serious adverse events related to NG-350A, with the oncolytic immunotherapy designed to drive intratumoral expression of a CD40 (search) agonist antibody.
Results could enable more patients to pursue organ-preserving "watch-and-wait" protocols instead of life-altering rectal surgery, particularly important as colorectal cancer (search) becomes the leading cause of cancer death in patients under 50.
Akamis Bio announced encouraging preliminary results from its Phase 1b FORTRESS study of NG-350A, an oncolytic immunotherapy for mismatch repair-proficient (pMMR) locally advanced rectal cancer (search) (LARC). The treatment combination achieved a 50% composite response rate across the first 10 patients who completed the 12-week active treatment period, with no serious adverse events or new safety signals identified related to NG-350A.
Clinical Trial Results Exceed Standard Care Expectations
The ongoing Phase 1b FORTRESS study is assessing the anti-tumor effects of NG-350A combined with chemoradiotherapy (search) (CRT) to establish whether the combination can improve composite response rates in pMMR LARC patients relative to expected outcomes from CRT alone. The primary endpoint is the composite response rate defined as the proportion of patients achieving a clinical complete response (cCR) or a near clinical complete response (ncCR) at 12 weeks.
The benchmark composite response rate for CRT alone at 12 weeks is approximately 25%. The preliminary 50% composite response rate observed in the FORTRESS study provides confirmation of results from the CEDAR study, an investigator-initiated trial of EnAd (a predecessor to NG-350A without a transgene) plus CRT in patients with LARC, which also demonstrated a 50% composite response rate.
"While still early data, observation of such a significant composite response rate with NG-350A plus CRT after only 12 weeks of treatment could be a significant development for locally advanced rectal cancer (search) treatment," said Eric Miller, MD, PhD, associate professor of radiation oncology at Ohio State University and a FORTRESS study investigator. "A therapy that increases the proportion of patients who respond to treatment, as well as the speed with which that response is achieved, could enable responding patients to pursue a 'watch-and-wait' protocol, to both avoid surgery and preserve organ function."
Addressing Growing Disease Burden in Younger Patients
LARC is defined by the spread of rectal cancer to nearby tissues or lymph nodes. Patients with pMMR tumors account for approximately 95% of all LARC cases, representing about 30,000 newly diagnosed patients annually in the US. Colorectal cancer (search) is now the leading cause of cancer-related death in patients under 50 years old in the US, and the incidence continues to rise in this younger population. Consistent with this trend, the average age of pMMR LARC patients included in this initial FORTRESS data analysis is 52 years.
The composite response rate used as the primary endpoint reflects the dynamic process of tumor regression. As a patient's tumor begins to respond to therapy, it moves through the ncCR phase (characterized by nearly complete disappearance of the tumor mass with some residual mucosal abnormality) before final achievement of a cCR (a return to fully healthy, normal mucosa). Achievement of a ncCR has been strongly predictive of subsequent achievement of a cCR, with up to 90% of ncCRs converting to cCRs following the initial assessment.
Mechanism of Action and Clinical Development
NG-350A is a clinical-stage, intravenously delivered Tumor-Specific Immuno-Gene (T-SIGn®) therapeutic designed to drive intratumoral expression of a CD40 (search) 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.
Study Design and Future Outlook
The Phase 1b FORTRESS study is an open-label, single-arm, and multicenter trial 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 treatment period, patients receive NG-350A plus CRT (oral capecitabine plus long-course intensity-modulated radiotherapy).
"We believe that these early FORTRESS data provide the first key evidence of clinical proof of concept for NG-350A plus CRT in pMMR LARC," said Howard Davis, PhD, CEO of Akamis Bio. "When treated with the current standard of care, patients need to undergo life-altering surgery to remove portions of the rectum. We believe that NG-350A plus CRT has the potential to advance the pMMR LARC standard of care, offering more patients access to a non-operative approach to management of their disease, as well as the opportunity for organ preservation – a critically important treatment goal as LARC continues to impact increasingly younger patient populations."
The FORTRESS study continues to enroll pMMR LARC patients with recruitment expected to conclude in 2H 2026. The data will be shared in a poster presentation on April 20th at the American Association for Cancer Research (AACR) Annual Meeting 2026 in San Diego.