NG-350A Plus Chemoradiotherapy for Locally Advanced Rectal Cancer

Phase 1

Recruiting

• Conditions: Locally Advanced Rectal Cancer (LARC)
• Interventions: Drug: NG-350A IV administration; Drug: Capecitabine oral administration; Radiation: Radiotherapy

• Registration Number: NCT06459869
• Lead Sponsor: Akamis Bio

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-06
• Study First Submitted: 2024-06-11
• Study First Submitted QC: 2024-06-13
• Study First Posted: 2024-06-14
• Study Start: 2025-04-07
• Last Update Submitted: 2025-05-23
• Last Update Posted: 2025-05-25
• Primary Completion: 2026-02-28
• Study Completion: 2029-01-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NG-350A plus CRT during a 12-week active study treatment period	Capecitabine oral administration	-
NG-350A plus CRT during a 12-week active study treatment period	Radiotherapy	-
NG-350A plus CRT during a 12-week active study treatment period	NG-350A IV administration	-

Primary Outcome Measures

Name	Time	Method
Proportion of patients achieving a clinical complete response (cCR)	12 weeks after initiating NG-350A in combination with chemoradiotherapy (CRT)

Secondary Outcome Measures

Name	Time	Method
MRI-based tumor regression grade (mrTRG)	12, 18, and 36 weeks after initiating NG-350A plus chemoradiotherapy (CRT)
Clinical response (CR) outcome	12, 18, and 36 weeks after initiating NG-350A plus chemoradiotherapy (CRT)
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

Trial Locations

Locations (3)

University College London NHS FT; 🇬🇧 London, United Kingdom

Ohio State University Comprehensive Cancer Center (OSU); 🇺🇸 Columbus, Ohio, United States

The University of Texas MD Anderson Cnacer Center; 🇺🇸 Houston, Texas, United States