NG-350A (CD40 agonist oncolytic adenoviral vector) + long-course CRT drives 80% near-cCR at W12 in pMMR LARC (FORTRESS Phase 1b)

NG-350A is an intravenously delivered, tumor-selective oncolytic adenoviral vector engineered to locally express an agonistic anti-CD40 antibody (immune-activating transgene), evaluated with standard long-course chemoradiotherapy (capecitabine-based CRT to 50Gy) in the Phase 1b FORTRESS trial (NCT06459869) for high-risk stage II/III pMMR locally advanced rectal cancer (cT3a–d, N0–2, MRF+ and/or EMVI+). In the first 10 enrolled patients, 5 were evaluable at week 12 and 4/5 (80%; all stage IIIB) achieved a near-complete clinical response (ncCR) by MRI TRG/endoscopy/DRE; ctDNA clearance (including 1 transient) was reported in all patients at or before W12. Safety to date appears manageable with no NG-350A-related SAEs or new signals; AEs were described as consistent with systemic viremia, with transient aPTT prolongation in 4 patients and no AEs attributed to the CD40 transgene—while historical long-course CRT alone typically yields ~20–30% clinical complete response and ~10–20% pathologic complete response, this early ncCR rate is well above expected but is based on only 5 evaluable patients and may shift with full cohort readout.