NCT06459869

Brief Summary

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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_1

Timeline
31mo left

Started Apr 2025

Typical duration for phase_1

Geographic Reach
2 countries

6 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress30%
Apr 2025Nov 2028

First Submitted

Initial submission to the registry

June 11, 2024

Completed
3 days until next milestone

First Posted

Study publicly available on registry

June 14, 2024

Completed
10 months until next milestone

Study Start

First participant enrolled

April 7, 2025

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 30, 2026

Expected
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 30, 2028

Last Updated

February 17, 2026

Status Verified

August 1, 2025

Enrollment Period

1.6 years

First QC Date

June 11, 2024

Last Update Submit

February 12, 2026

Conditions

Locally Advanced Rectal Cancer (LARC)

Keywords

Treatment naiveOligometastatic

Outcome Measures

Primary Outcomes (1)

  • Proportion of patients achieving a response (ncCR / cCR)

    12 weeks after initiating NG-350A in combination with chemoradiotherapy (CRT)

Secondary Outcomes (3)

  • Incidence and severity of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

    1-3 years

  • Clinical response (CR) outcome

    12, 18, and 36 weeks after initiating NG-350A plus chemoradiotherapy (CRT)

  • MRI-based tumor regression grade (mrTRG)

    12, 18, and 36 weeks after initiating NG-350A plus chemoradiotherapy (CRT)

Study Arms (1)

NG-350A plus CRT during a 12-week active study treatment period

EXPERIMENTAL
Drug: NG-350A IV administrationDrug: Capecitabine oral administrationRadiation: Radiotherapy

Interventions

NG-350A IV administrationDRUG

a tumour-selective anti-CD40-expressing adenoviral vector

NG-350A plus CRT during a 12-week active study treatment period
Capecitabine oral administrationDRUG

chemotherapy

NG-350A plus CRT during a 12-week active study treatment period
RadiotherapyRADIATION

long-course intensity-modulated radiotherapy

NG-350A plus CRT during a 12-week active study treatment period

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

AdventHealth Orlando

Orlando, Florida, 32804, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

University College London NHS FT

London, United Kingdom

RECRUITING

The Royal Marsden NHS Foundation Trust

Sutton, United Kingdom

RECRUITING

Related Publications (1)

  • Naing A, Khalil D, Rosen O, Camidge DR, Lillie T, Ji RR, Stacey A, Thomas M, Rosen L. First-in-human clinical outcomes with NG-350A, an anti-CD40 expressing tumor-selective vector designed to remodel immunosuppressive tumor microenvironments. J Immunother Cancer. 2024 Oct 15;12(10):e010016. doi: 10.1136/jitc-2024-010016.

    PMID: 39414325DERIVED

Related Links

MeSH Terms

Interventions

Radiotherapy

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Vice President Head of Clinical Operations

CONTACT

+1 (484) 362-8918robert.maietta@akamisbio.com

https://www.FortressStudy.org

CONTACT

oliver.rosen@akamisbio.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 11, 2024

First Posted

June 14, 2024

Study Start

April 7, 2025

Primary Completion (Estimated)

November 30, 2026

Study Completion (Estimated)

November 30, 2028

Last Updated

February 17, 2026

Record last verified: 2025-08

Locations

GB(2)US(4)