Overview

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.

Eligibility

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.