Clinical trial NCT06459869: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Locally Advanced Rectal Cancer (LARC)
Lead sponsor: Akamis Bio
Sponsor class: INDUSTRY
First posted: 2024-06-14
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Proportion of patients achieving a clinical complete response (cCR)
timeFrame: 12 weeks after initiating NG-350A in combination with chemoradiotherapy (CRT)
Secondary outcomes:
measure: Incidence and severity of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
timeFrame: 1-3 years
measure: Clinical response (CR) outcome
timeFrame: 12, 18, and 36 weeks after initiating NG-350A plus chemoradiotherapy (CRT)
measure: MRI-based tumor regression grade (mrTRG)
timeFrame: 12, 18, and 36 weeks after initiating NG-350A plus chemoradiotherapy (CRT)
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center (OSU)
state: Ohio
city: Houston
country: United States
facility: The University of Texas MD Anderson Cnacer Center
state: Texas
city: London
country: United Kingdom
facility: University College London NHS FT
Study officials:
References: