Akamis Bio Reports Promising Early Findings from Phase 1b FORTRESS Trial of NG-350A in MMR-Proficient Locally Advanced Rectal Cancer
Akamis Bio, a biotechnology company focused on transforming the treatment landscape for colorectal cancer, has reported encouraging early clinical data from its ongoing Phase 1b FORTRESS study evaluating NG-350A, a novel oncolytic immunotherapy. The findings, presented at the American Association for Cancer Research Annual Meeting 2026 in San Diego, highlight the potential of NG-350A in combination with standard chemoradiotherapy (CRT) to significantly improve outcomes in patients with mismatch repair-proficient (pMMR) locally advanced rectal cancer (LARC).
The interim results, based on the first cohort of patients completing the initial 12-week treatment period, demonstrated a composite response rate of 50 percent. This metric includes both clinical complete responses (cCR) and near clinical complete responses (ncCR), and notably exceeds the approximate 25 percent benchmark historically associated with CRT alone. Equally important, the therapy combination was well tolerated, with no serious adverse events or unexpected safety concerns attributed to NG-350A, reinforcing its favorable safety profile at this stage of development.
The Phase 1b FORTRESS study (ClinicalTrials.gov Identifier: NCT06459869) has been designed to assess whether adding NG-350A to CRT can enhance anti-tumor activity compared to standard treatment alone. The trial specifically targets patients with pMMR LARC, a subgroup that accounts for the vast majority—approximately 95 percent—of all locally advanced rectal cancer cases. In the United States alone, this corresponds to an estimated 30,000 newly diagnosed patients each year, underscoring the substantial clinical need for improved therapies in this population.
Rectal cancer, particularly in its locally advanced stages, presents significant treatment challenges. LARC is characterized by tumor spread to nearby tissues or lymph nodes, often necessitating aggressive multimodal therapy. The current standard of care typically involves chemoradiotherapy followed by surgical resection of the affected portion of the rectum. While this approach can be effective in controlling disease, it frequently results in long-term complications, including impaired bowel function, permanent colostomies, and a significant reduction in quality of life.
The FORTRESS study aims to address these limitations by exploring a non-surgical treatment paradigm. Its primary endpoint—the composite response rate at 12 weeks—captures the proportion of patients achieving either a cCR or ncCR. These endpoints reflect different stages of tumor regression. A near clinical complete response indicates that the tumor has nearly disappeared, with only minimal residual abnormalities, while a clinical complete response signifies the absence of detectable tumor and restoration of normal tissue.
This distinction is clinically meaningful because tumor regression is often a gradual process. Patients may initially achieve an ncCR before progressing to a full cCR over time. Importantly, previous studies have shown that up to 90 percent of patients who reach an ncCR eventually convert to a cCR, making ncCR a strong predictor of ultimate treatment success. By incorporating both measures, the composite response rate provides a more comprehensive and dynamic assessment of therapeutic efficacy.
The 50 percent composite response rate observed in the FORTRESS study aligns closely with results from the earlier CEDAR study, an investigator-initiated trial that evaluated EnAd—an earlier version of the therapy lacking the transgene component—also in combination with CRT. The consistency between these studies not only validates the underlying approach but also suggests that NG-350A, with its enhanced design, may offer additional therapeutic benefits.
NG-350A is an oncolytic immunotherapy engineered to selectively infect and replicate within tumor cells, leading to their destruction while simultaneously stimulating an anti-tumor immune response. By combining this mechanism with chemoradiotherapy, which itself can increase tumor susceptibility to immune attack, the therapy aims to create a synergistic effect that enhances overall treatment efficacy.
According to Eric Miller, MD, PhD, associate professor of radiation oncology at Ohio State University and an investigator in the FORTRESS study, the early findings are particularly promising given the relatively short treatment duration. He noted that achieving such a high composite response rate within just 12 weeks could represent a meaningful advancement in the management of locally advanced rectal cancer.
Miller emphasized that therapies capable of increasing both the proportion of responding patients and the speed of response could fundamentally change treatment strategies. Specifically, they could enable more patients to adopt a “watch-and-wait” approach, in which surgery is deferred or avoided altogether in favor of careful monitoring. This strategy has gained increasing interest in recent years as a way to preserve organ function and improve quality of life without compromising oncologic outcomes.
The potential for organ preservation is particularly important in light of evolving epidemiological trends in colorectal cancer. The disease has become the leading cause of cancer-related death among individuals under the age of 50 in the United States, with incidence rates continuing to rise in younger populations. Reflecting this trend, the average age of patients included in the initial FORTRESS analysis was 52 years, highlighting the growing impact of LARC on individuals in the prime of their lives.
Howard Davis, PhD, Chief Executive Officer of Akamis Bio, described the early data as a critical milestone in the development of NG-350A. He noted that the findings provide initial clinical proof of concept for the therapy in combination with CRT, supporting its potential to redefine the standard of care for pMMR LARC.
Davis pointed out that current treatment approaches often require patients to undergo life-altering surgical procedures, which can have lasting physical and psychological consequences. By contrast, NG-350A plus CRT may offer a path toward non-operative disease management for a greater proportion of patients. This shift could not only reduce the burden of treatment but also align more closely with patient preferences, particularly among younger individuals who may prioritize long-term quality of life and functional outcomes.
The broader implications of these findings extend beyond rectal cancer. As an oncolytic immunotherapy platform, NG-350A represents part of a growing class of treatments designed to harness the body’s immune system to fight cancer more effectively. By integrating tumor-selective viral therapy with established treatment modalities, Akamis Bio is exploring new ways to enhance anti-tumor responses while minimizing toxicity.
The data presented at AACR 2026 mark an important step forward, but further research will be needed to confirm these early results in larger patient populations and over longer follow-up periods. The ongoing FORTRESS study will continue to enroll and evaluate patients, providing additional insights into the durability of responses, long-term safety, and potential survival benefits associated with NG-350A.
If the promising early findings are borne out in subsequent analyses, NG-350A could play a transformative role in the treatment of pMMR locally advanced rectal cancer. By improving response rates, accelerating tumor regression, and enabling organ-preserving strategies, the therapy has the potential to significantly enhance both clinical outcomes and quality of life for patients facing this challenging disease.
As the oncology community continues to seek more effective and less invasive treatment options, innovations like NG-350A underscore the importance of integrating novel biological approaches with existing standards of care. The progress reported by Akamis Bio at AACR 2026 offers a glimpse into a future where cancer treatment is not only more effective but also more patient-centered, with an emphasis on preserving function, reducing morbidity, and delivering durable, meaningful responses.
About NG-350A
NG-350A is a clinical-stage, intravenously delivered Tumor-Specific Immuno-Gene (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 the FORTRESS Study
The Phase 1b FORTRESS study (NCT06459869) is an open-label, single-arm, and multicenter trial of NG-350A in combination with chemoradiotherapy (CRT) in adult patients with mismatch repair-proficient (pMMR) locally advanced rectal cancer (LARC) and at least one risk factor for local or distant recurrence or with oligometastatic disease. The FORTRESS study builds upon the Akamis Bio-supported CEDAR study which showed a significantly greater composite response rate in LARC patients treated with a combination of Akamis Bio’s first generation oncolytic immunotherapy (EnAd) and chemoradiotherapy (CRT), relative to expected outcomes using standard-of-care CRT alone.
The FORTRESS 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 treatment period, patients will receive NG-350A plus CRT (oral capecitabine plus long-course intensity-modulated radiotherapy). The primary endpoint of the FORTRESS study 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.
Key secondary endpoints include the incidence and severity of adverse events, characterization of the anti-tumor effects of NG-350A in combination with CRT (including clinical response outcome and magnetic resonance tumor reduction grade [mrTRG]), and measurement of levels of circulating tumor DNA (ctDNA) clearance. The FORTRESS study continues to enroll pMMR LARC patients with recruitment expected to conclude in 2H 2026. Patients recently diagnosed with pMMR LARC interested in learning more about the FORTRESS trial can visit www.FortressStudy.org.
About Locally Advanced Rectal Cancer (LARC)
Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States, and it has recently emerged as the leading cause in patients under 50 years of age. There are 159,000 people newly diagnosed with CRC each year, with about 53,000 of those people diagnosed specifically with rectal cancer of which approximately 30,000 are diagnosed with LARC.
LARC is defined by the spread of 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. Approximately 95 percent of LARC patients have mismatch repair-proficient (pMMR) tumors which have a functional DNA repair system.
About Akamis Bio
Headquartered in Cambridge, Massachusetts, Akamis Bio is a clinical-stage oncology company developing systemically administered oncolytic immunotherapies to treat colorectal cancer, with an initial focus on locally advanced rectal cancer (LARC). Its proprietary Tumor-Specific Immuno-Gene Therapy (T-SIGn®) platform is designed to deliver novel immunotherapeutic proteins, biomolecules and transgene combinations to treat solid tumors, with its lead clinical-stage program, NG-350A, driving intratumoral expression of a CD40 agonist monoclonal antibody.
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