Locally Advanced Rectal Cancer (LARC)Phase 1FORTRESSNCT06459869
NG-350A Plus Chemoradiotherapy for Locally Advanced Rectal Cancer
A Phase 1 study testing NG-350A IV administration, Capecitabine oral administration and Radiotherapy in people with Locally Advanced Rectal Cancer (LARC), run by Akamis Bio at 7 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Rectal Cancer (LARC)
- What is being tested?
- NG-350A IV administration, Capecitabine oral administration and Radiotherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 7 Apr 2025to 30 Jan 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States5 sites
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
University of Southern California
Los Angeles, California, 90033
AdventHealth Orlando
Orlando, Florida, 32804
Washington University School of Medicine
St Louis, Missouri, 63110
United Kingdom2 sites
University College London NHS FT
London
The Royal Marsden NHS Foundation Trust
Sutton
About this study
Official title: 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.
- Conditions
- Locally Advanced Rectal Cancer (LARC)
- Being tested
- NG-350A IV administration, Capecitabine oral administration, Radiotherapy
- Keywords
- Treatment naive, Oligometastatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NG-350A IV administrationDrug
a tumour-selective anti-CD40-expressing adenoviral vector
Capecitabine oral administrationDrug
chemotherapy
RadiotherapyRadiation
long-course intensity-modulated radiotherapy
| Study group | Role | What they receive |
|---|---|---|
| NG-350A plus CRT during a 12-week active study treatment period | Experimental | Not described Receives: Drug: NG-350A IV administration; Drug: Capecitabine oral administration; Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients achieving a response (ncCR / cCR)
Measured: 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
Measured: 1-3 years
Clinical response (CR) outcome
Measured: 12, 18, and 36 weeks after initiating NG-350A plus chemoradiotherapy (CRT)
MRI-based tumor regression grade (mrTRG)
Measured: 12, 18, and 36 weeks after initiating NG-350A plus chemoradiotherapy (CRT)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2024
- Study start7 Apr 2025
- Primary completion30 Jan 2027 (estimated)
- Study completion30 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced Rectal Cancer (LARC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Akamis Bio
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06459869
- Sponsor's protocol ID
- NG-350A-03
- Other IDs
- https://www.FortressStudy.org
- Acronym
- FORTRESS
- Status last verified
- Sep 2026
- First submitted
- 11 Jun 2024
- Last updated
- 3 Nov 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 39414325
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT06459869
- Acronym / sponsor ID
- FORTRESS / NG-350A-03
- Conditions
- Locally Advanced Rectal Cancer (LARC)
- Keywords
- Treatment naive, Oligometastatic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Akamis BioIndustry (pharma, biotech, devices)
- Study start
- 7 Apr 2025 (actual)
- Primary completion
- 30 Jan 2027 (estimated)
- Study completion
- 30 Jan 2029 (estimated)
- First posted
- 14 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NG-350A plus CRT during a 12-week active study treatment period | Experimental | Drug: NG-350A IV administration, Drug: Capecitabine oral administration, Radiation: Radiotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NG-350A IV administrationa tumour-selective anti-CD40-expressing adenoviral vector | Drug | NG-350A plus CRT during a 12-week active study treatment period |
| Capecitabine oral administrationchemotherapy | Drug | NG-350A plus CRT during a 12-week active study treatment period |
| Radiotherapylong-course intensity-modulated radiotherapy | Radiation | NG-350A plus CRT during a 12-week active study treatment period |
Primary outcome
Proportion of patients achieving a response (ncCR / cCR)
Time frame: 12 weeks after initiating NG-350A in combination with chemoradiotherapy (CRT)
3 secondary outcomes
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
Clinical response (CR) outcome
Time frame: 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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- Derived from this study: PubMed 39414325Naing 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.
- Fortress Study InformationLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NG-350A IV administration, Capecitabine oral administration and Radiotherapy in people with Locally Advanced Rectal Cancer (LARC), run by Akamis Bio at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients achieving a response (ncCR / cCR) (time frame: 12 weeks after initiating NG-350A in combination with chemoradiotherapy (CRT)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06459869, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.