NG-350A combined with chemoradiotherapy for advanced rectal cancer

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)

This study is testing if adding a new drug called NG-350A to standard chemotherapy and radiation can help adults with advanced rectal cancer who are at risk of their cancer coming back.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Akamis Bio (Industry-sponsored)
• Drugs / interventions: prednisone
• Locations: 6 sites (Orlando, Florida and 5 other locations)
• Trial ID: NCT06459869 on ClinicalTrials.gov

What this trial studies

This trial evaluates the safety and efficacy of NG-350A in conjunction with chemoradiotherapy for adults diagnosed with locally advanced rectal cancer (LARC) who have at least one risk factor for recurrence. It is an open-label, single-arm, multicenter trial that aims to determine how well this combination treatment works. Participants will receive NG-350A intravenously, along with oral Capecitabine and radiotherapy as part of their treatment regimen. The study focuses on patients with specific eligibility criteria, including confirmed adenocarcinoma and microsatellite stable status.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed locally advanced rectal cancer who are suitable for neoadjuvant chemoradiotherapy.

Not a fit: Patients with recurrent rectal cancer or distant metastatic disease are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with locally advanced rectal cancer by reducing the risk of recurrence.

How similar studies have performed: Other studies have shown promise with similar approaches, but this specific combination is being evaluated for the first time.

Eligibility criteria

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

Where this trial is running

Orlando, Florida and 5 other locations

• AdventHealth Orlando — Orlando, Florida, United States (Recruiting)
• Washington University School of Medicine — St Louis, Missouri, United States (Recruiting)
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States (Recruiting)
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• University College London NHS FT — London, United Kingdom (Recruiting)
• The Royal Marsden NHS Foundation Trust — Sutton, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Vice President Head of Clinical Operations

Conditions Locally Advanced Rectal Cancer; Treatment naive; Oligometastatic