NG-350A Plus Chemoradiotherapy for Locally Advanced Rectal Cancer (FORTRESS)

February 12, 2026 updated by: Akamis Bio

A Multicentre, Open-label, Non-randomized, Phase 1b Trial of NG-350A, a Tumour-selective Anti-CD40-expressing Adenoviral Vector, in Combination With Chemoradiotherapy in Locally Advanced Rectal Cancer (FORTRESS)

The FORTRESS trial (NG-350A-03) is an open-label, single-arm, and multicentre 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
      • London, United Kingdom
        • Recruiting
        • University College London NHS FT
        • Principal Investigator:
          • Maria Hawkins
      • Sutton, United Kingdom
        • Recruiting
        • The Royal Marsden NHS Foundation Trust
        • Principal Investigator:
          • Sheela Rao
  • United States
    • Florida
      • Orlando, Florida, United States, 32804
        • Recruiting
        • AdventHealth Orlando
        • Principal Investigator:
          • Mohamedtaki Tejani
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Principal Investigator:
          • Moh'd Khushman
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Comprehensive Cancer Center
        • Principal Investigator:
          • Eric Miller
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas MD Anderson Cancer Center
        • Principal Investigator:
          • Sonal Noticewala

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Selected Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the rectum.
  • Locally advanced disease (clinical stage II-III based on pelvic MRI) selected by a multidisciplinary team for treatment with neoadjuvant CRT (which may be followed by CNCT to comprise planned TNT). Patients with oligometastatic disease are permitted provided that the site-specific multidisciplinary team deems them suitable for radical treatment/chemoradiation.
  • Confirmed microsatellite stable (MSS)/proficient mismatch repair (pMMR) status.
  • Provide written informed consent to participate.
  • ECOG Performance Status 0 or 1.
  • Must not be pregnant or breastfeeding.
  • Patients who are sexually active (with either sex) must agree to comply with contraceptive requirements.
  • Adequate lung reserve, renal function, hepatic function, and bone marrow/hematological function assessed ≤ 10 days prior to first dose.

Selected Exclusion Criteria:

  • Recurrent rectal cancer.
  • Distant metastatic disease not amenable to radical treatment/chemoradiation.
  • Other prior malignancy active within the previous 3 years, except for local or organ confined early-stage cancer that has been definitively treated with curative intent, does not require ongoing treatment, has no evidence of residual disease, and has a negligible risk of recurrence and is therefore unlikely to interfere with the primary and secondary endpoints of the trial, including response rate and safety.
  • Splenectomy (patients with prior partial resection remain eligible if the Investigator considers splenic function to not be significantly compromised).
  • Active autoimmune disease that has required systemic therapy in the past 2 years, immunocompromised status in the opinion of the Investigator, or current treatment with systemic immunosuppressive therapy (daily prednisone equivalent for chronic system replacement not to exceed 10mg per day).
  • Infectious or inflammatory bowel disease in the 3 months before the first dose of study treatment.
  • Any clinically significant cardiovascular, peripheral vascular, cerebrovascular, or thromboembolic event in the last 1 month before the first dose of study treatment.
  • Major surgery in the 14 days before the first dose of study treatment or any surgical wounds that are not fully healed and free of infection or dehiscence.
  • Any prior surgery for rectal cancer or pelvic radiotherapy.
  • Any other anti-cancer or experimental therapy within the previous 12 months or that is planned during the active study treatment period.
  • Treatment with any other enadenotucirev-based virus (parent virus or transgene-modified variants), or anti-CD40 antibody at any time.
  • History of prior Grade 3-4 acute kidney injury or other clinically significant renal impairment.
  • Any ongoing Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 coagulation abnormality/coagulopathy.

URL:

https://www.FortressStudy.org

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NG-350A plus CRT during a 12-week active study treatment period
Drug: NG-350A IV administration
a tumour-selective anti-CD40-expressing adenoviral vector
Drug: Capecitabine oral administration
chemotherapy
Radiation: Radiotherapy
long-course intensity-modulated radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Proportion of patients achieving a response (ncCR / cCR)
Time Frame: 12 weeks after initiating NG-350A in combination with chemoradiotherapy (CRT)
12 weeks after initiating NG-350A in combination with chemoradiotherapy (CRT)

Secondary Outcome Measures

Outcome Measure
Time Frame
Incidence and severity of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Time Frame: 1-3 years
1-3 years
Clinical response (CR) outcome
Time Frame: 12, 18, and 36 weeks after initiating NG-350A plus chemoradiotherapy (CRT)
12, 18, and 36 weeks after initiating NG-350A plus chemoradiotherapy (CRT)
MRI-based tumor regression grade (mrTRG)
Time Frame: 12, 18, and 36 weeks after initiating NG-350A plus chemoradiotherapy (CRT)
12, 18, and 36 weeks after initiating NG-350A plus chemoradiotherapy (CRT)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Akamis Bio

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 7, 2025

Primary Completion (Estimated)

November 30, 2026

Study Completion (Estimated)

November 30, 2028

Study Registration Dates

First Submitted

June 11, 2024

First Submitted That Met QC Criteria

June 13, 2024

First Posted (Actual)

June 14, 2024

Study Record Updates

Last Update Posted (Actual)

February 17, 2026

Last Update Submitted That Met QC Criteria

February 12, 2026

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NG-350A-03
  • https://www.FortressStudy.org (Other Identifier: Akamis Bio)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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