Combining DCSZ11 With Radiation and Chemotherapy as Neoadjuvant Treatment for pMMR Locally Advanced Rectal Cancer

Inclusion Criteria:

• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1.
• Rectal cancer (with tumor tissue present at or below the peritoneal reflection) as determined by MRI pelvis or endoscopic ultrasound.
• Have histologically proven mismatch repair proficient (pMMR) or microsatellite stable (MSS) rectal adenocarcinoma.
• Must not have received any prior systemic treatment or radiation.

• Patients have the following clinical staging:

  • cT4 any node status
  • Any T stage cN2 node status
  • Any T or N status, evidence of suspicious lateral lymph nodes > 10 mm in size in short axis
  • Evidence of extramural vascular invasion on MRI pelvis
• Absence of distant metastases on CT or MRI imaging
• Patients must have adequate organ and marrow function defined by study-specified laboratory tests and procedures.
• Left ventricular ejection fraction (LVEF) assessment with documented LVEF ≥ 50% by either TTE or Multigated Acquisition (MUGA) (TTE preferred) within 6 months from first study drug administration.
• For both Women and Men, must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

• Have received an investigational agent or used an investigational device within 28 days of the first dose of study drug.
• Have expected to require any other form of systemic or localized antineoplastic therapy while on study.
• Have had surgery within 28 days of dosing of investigational agent, excluding minor procedures (dental work, skin biopsy, etc.).
• History of severe hypersensitivity reaction to any monoclonal antibody.
• History of encephalitis, meningitis, dementia, Parkinson's or uncontrolled seizures within 1 year prior to the first dose of study drug.
• Uncontrolled infection of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), or Tuberculosis.
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
• Any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft.
• Patient has a pulse oximetry of <92% on room air.
• Patient is on supplemental home oxygen.
• Has clinically significant heart disease.
• Conditions, including alcohol or drug dependence that would affect the patient's ability to comply with study visits and procedures.
• Patient is pregnant or breastfeeding.
• Unwilling or unable to follow the study schedule for any reason.
• Patient received a live vaccine within 30 days of planned start of study medication.
• Receipt of COVID-19 vaccination within 1 week of planned start of study medication or for which the planned COVID-19 vaccinations would not be completed 1 week prior to start of study medication.