NG-350A Plus Chemoradiotherapy for Locally Advanced Rectal Cancer

Official title

A Multicentre, Open-label, Non-randomized, Phase 1b Trial of NG-350A, a Tumour-selective Anti-CD40-expressing Adenoviral Vector, in Combination With Chemoradiotherapy in Locally Advanced Rectal Cancer (FORTRESS)

Overview

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

• Drug NG-350A IV administration
  a tumour-selective anti-CD40-expressing adenoviral vector
• Drug Capecitabine oral administration
  chemotherapy
• Radiation Radiotherapy
  long-course intensity-modulated radiotherapy

Primary outcome measures

• Proportion of patients achieving a response (ncCR / cCR) [Time frame: 12 weeks after initiating NG-350A in combination with chemoradiotherapy (CRT)]

Secondary outcome measures (3)

• Incidence and severity of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 [Time frame: 1-3 years]
• Clinical response (CR) outcome [Time frame: 12, 18, and 36 weeks after initiating NG-350A plus chemoradiotherapy (CRT)]
• MRI-based tumor regression grade (mrTRG) [Time frame: 12, 18, and 36 weeks after initiating NG-350A plus chemoradiotherapy (CRT)]

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.

URL:

https://www.FortressStudy.org

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 5 centers

• University of Southern California — Los Angeles
• AdventHealth Orlando — Orlando
• Washington University School of Medicine — St Louis
• Ohio State University Comprehensive Cancer Center — Columbus
• The University of Texas MD Anderson Cancer Center — Houston

United Kingdom · 2 centers

• University College London NHS FT — London
• The Royal Marsden NHS Foundation Trust — Sutton

Publications

• Naing A, Khalil D, Rosen O, Camidge DR, Lillie T, Ji RR, Stacey A, Thomas M, Rosen L. First-in-human clinical outcomes with NG-350A, an anti-CD40 expressing tumor-selective vector designed to remodel immunosuppressive tumor microenvironments. J Immunother Cancer. 2024 Oct 15;12(10):e010016. doi: 10.1136/jitc-2024-010016. PMID 39414325

Identifiers

NCT: NCT06459869 · NG-350A-03 · https://www.FortressStudy.org

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗