ng-350a plus chemoradiotherapy for locally advanced rectal cancer

Conditions: Locally Advanced Rectal Cancer (LARC)

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.


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.