NG-350A Plus Chemoradiotherapy for Locally Advanced Rectal Cancer

About

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.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 1

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

18 Years

Maximum Age

N/A

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.