Locally Advanced Rectal Cancer (LARC)
Conditions
Keywords
Treatment naive, Oligometastatic
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.
Interventions
DRUGNG-350A IV administration
a tumour-selective anti-CD40-expressing adenoviral vector
DRUGCapecitabine oral administration
chemotherapy
RADIATIONRadiotherapy
long-course intensity-modulated radiotherapy
Sponsors
Akamis Bio
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of patients achieving a response (ncCR / cCR) | 12 weeks after initiating NG-350A in combination with chemoradiotherapy (CRT) |
Secondary
| 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 | 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) |
Countries
United Kingdom, United States
Outcome results
None listed