| Eligibility |
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.
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