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

Combining CD93 Inhibition (DCSZ11) With Short Course Radiation and Chemotherapy as Part of Total Neoadjuvant Treatment (TNT) for High-risk Mismatch Repair Proficient (pMMR) Locally Advanced Rectal Cancer (LARC)

The purpose of this study is to evaluate the safety and clinical activity of combining DCSZ11 with radiation and capecitabine/oxaliplatin (CAPOX) for the neoadjuvant treatment of patients with mismatch repair proficient (pMMR) high risk locally advanced rectal cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: DCSZ11; Radiation: Radiation; Drug: Capecitabine; Drug: Oxaliplatin

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Colleen Apostal, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins SKCCC
      • Principal Investigator: Eric Christenson, MD
      • Contact: Colleen Apostol, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: DCSZ11 with Chemotherapy

Drug: DCSZ11; Patients will receive a lead in dose of DCSZ11 (1200 mg administered IV). Three weeks after the lead-in dose, DCSZ11 (1200 mg administered IV) will be administered on Day 1 of each 21 day cycle for a total of 6 cycles of treatment.; Radiation: Radiation; Patients will receive a short course of radiation (5 Gy for 5 days) two weeks after they receive their lead-in dose of DCSZ11.; Drug: Capecitabine; Patients will receive Capecitabine (1000mg/m^2 administered by mouth twice a day) will be administered on Days 1 through 14 of each 21 day cycle for a total of 6 cycles of treatment.; Other Names: Xeloda; Drug: Oxaliplatin; Patients will receive Oxaliplatin (130mg/m^2 administered IV) will be administered on Day 1 of each 21 day cycle for a total of 6 cycles of treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Complete Response (compCR) Rate	compCR is defined as the proportion of subjects with a pathologic complete response at the time of surgical resection or complete clinical response. Pathologic complete response is defined as subjects with no viable tumor cell noted on pathological evaluation of the resection specimen using the College of American Pathologists (CAP) tumor regression scoring system (CAP tumor regression score of 0). Complete clinical response is defined as subjects with an absence of tumor on endoscopy and no evidence of metastatic disease or recurrence on imaging for 1 year from the end of treatment.	24 months
Number of participants experiencing a drug-related toxicity requiring treatment discontinuation	Defined using NCI CTCAE v6.0	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Response Rate	Pathologic response rate as defined as the proportion of subjects with complete or partial tumor regression at the time of surgery using the College of American Pathologists (CAP) tumor regression scoring system (CAP tumor regression score of 0 to 2).	8 months
Event-Free Survival (EFS)	EFS is defined as the number of months from the date of first dose to relapsed disease, development of metastatic disease, or death due to any cause. EFS will be censored at the date of the last scan for subjects without documentation of disease progression at the time of analysis. Estimation based on the Kaplan-Meier curve.	24 months

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: DynamiCure Biotechnology
• Investigators: Principal Investigator: Eric Christenson, MD, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Medical Institution

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): July 1, 2030

Study Registration Dates

• First Submitted: May 5, 2026
• First Submitted That Met QC Criteria: May 11, 2026
• First Posted (Actual): May 12, 2026

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Physical Phenomena; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Oxaliplatin; Radiation
• Other Study ID Numbers: J2652; IRB00536619 (Other Identifier: Johns Hopkins Medical Institution)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No