Irinotecan liposome with capecitabine and enronsubemab plus short-course radiotherapy before surgery for locally advanced rectal cancer

The Combination of Irinotecan Liposome, Capecitabine and Enlansubemab Embedded in Short-course Radiotherapy as Neoadjuvant Therapy for Locally Advanced Rectal Cancer: a Prospective, Single-center and Single-arm Study

This trial will test whether giving irinotecan liposome, capecitabine, and enronsubemab together with a short course of radiotherapy before surgery can better shrink locally advanced rectal cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Tianjin Medical University Cancer Institute and Hospital (Academic / other)
• Drugs / interventions: enlansubemab, chemotherapy, immunotherapy, prednisone, enronsubemab
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT07281157 on ClinicalTrials.gov

What this trial studies

This is a prospective, single-center, single-arm phase 2 trial of a combined neoadjuvant regimen for locally advanced rectal adenocarcinoma. Participants receive irinotecan liposome, capecitabine, and enronsubemab administered together with short-course radiotherapy prior to planned surgery. Eligible patients are adults with cT3-4 or node-positive rectal cancer, tumors within 10 cm of the anal verge, ECOG 0–1, and adequate organ function. The study aims to observe tumor response and the safety profile of this combined approach in the preoperative setting.

Who should consider this trial

Good fit: Ideal candidates are adults 18–75 with histologically confirmed locally advanced rectal adenocarcinoma (cT3-4 or N+), tumors ≤10 cm from the anal verge, ECOG 0–1, adequate blood, liver and kidney function, and no prior anti-tumor treatment for this cancer.

Not a fit: Patients with poor performance status, inadequate organ function, prior rectal cancer treatment, metastatic disease outside the study criteria, or inability to attend treatment in Tianjin are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the regimen could increase tumor shrinkage before surgery and improve the chances of complete removal or organ preservation.

How similar studies have performed: Short-course radiotherapy combined with systemic chemotherapy has shown promising results in other neoadjuvant rectal cancer programs, but adding enronsubemab is a newer approach with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

1. Age of 18-75 years old;
2. rectal adenocarcinoma confirmed by histology and/or cytology;
3. locally advanced rectal cancer cT3-4 or N+ confirmed by baseline examination (AJCC/UICC TNM staging (8th edition, 2017);
4. Distance from lower margin to anal margin ≤ 10 cm;
5. Patients with at least one assessable lesion according to RECIST1.1 criteria;
6. ECOG 0-1;
7. the expected survival time was more than 12 months;
8. had not received anti-tumor treatment for rectal cancer after diagnosis, including radiotherapy, chemotherapy, surgery, etc.
9. Bone marrow function: absolute neutrophil count (ANC) ≥1.5×109/L, hemoglobin ≥90g/dL, platelet (PLT) ≥100×109/L, white blood cell (WBC) ≥3.0×109/L;
10. Liver function: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) ≤2.5 times the upper limit of normal (ULN), if there is liver metastasis ≤5×ULN, total bilirubin \<1.5 ULN;
11. Renal function: serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (CCr) ≥60mL/min (according to Cockcroft-Gault formula);
12. Coagulation function: prothrombin time (PT), activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤1.5×ULN;
13. exclude active or suspected infection;
14. non-pregnant or lactating women; Women/men of childbearing age should use effective contraception during the study and for 6 months after the end of study treatment;
15. The patients had good compliance, understood the research process of this study, and signed the written informed consent.

Exclusion Criteria:

1. patients with other malignant tumors (except cured carcinoma in situ and basal cell carcinoma) in the past 5 years;
2. patients with mismatch repair deficiency (dMMR) or microsatellite instability high (MSI-H);
3. obvious clinical bleeding symptoms or obvious bleeding tendency within 3 months before treatment (bleeding \> 30 mL within 3 months, hematemesis, melena, hematochezia), hemoptysis (fresh blood \> 5 mL within 4 weeks), etc. Or treatment for a venous/venous thrombotic event within the previous 6 months, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism; Long-term anticoagulation with warfarin or heparin or long-term antiplatelet therapy (aspirin ≥300 mg/ day or clopidogrel ≥75 mg/ day) may be required.
4. extensive distant metastasis (e.g., peritoneal metastasis, multiple bone/brain metastases);
5. patients who had used potent CYP3A4 inducers at the same time within 3 weeks before the first dose, or had used potent CYP3A4 inhibitors or potent UGT1A1 inhibitors within 3 weeks before the first dose;
6. patients who underwent major organ surgery (excluding needle biopsy, central venous catheterization, port catheterization, stent placement to relieve biliary obstruction, percutaneous hepatobiliary drainage, cholecystostomy) or elective surgery within 4 weeks before treatment;
7. tumor invasion of large vascular structures, such as pulmonary artery, superior vena cava or inferior vena cava, and there is a high risk of bleeding according to the investigator's judgment;
8. Active heart disease (including myocardial infarction, severe/unstable angina) within 6 months before treatment. Echocardiography showed that the left ventricular ejection fraction was less than 50% and the arrhythmia was not well controlled.
9. have hypertension that is not well controlled with antihypertensive medication (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg);
10. subjects with active infection or fever of unknown origin \>38.5 degrees during screening or before the first dose of medication (according to the investigator's assessment, subjects with fever due to cancer could be enrolled);
11. subjects with congenital or acquired immunodeficiency, such as HIV infection or active hepatitis (transaminase did not meet the inclusion criteria, hepatitis B reference: HBV DNA≥1000 IU/ml; hepatitis C reference: HCV RNA≥1000 IU/ml); Chronic hepatitis B virus carriers, HBV DNA \< 2000 IU/ml, must receive antiviral therapy at the same time during the trial.
12. any other medical condition, clinically significant metabolic abnormality, physical examination abnormality, or laboratory abnormality where there is reason to suspect that the patient has a disease or condition (such as having seizures requiring treatment) that would be inappropriate for the study drug, in the investigator's judgment, or that would affect interpretation of the study results or place the patient at high risk;
13. intestinal obstruction (except incomplete intestinal obstruction requiring only enteral nutrition); Subjects at risk of intestinal perforation (including, but not limited to, a history of acute diverticulitis, abdominal abscess, or abdominal cancer); 14 History of wide bowel resection (partial colectomy or wide small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.

(15) received any other antibodies/drugs (including PD-1, PD-L1, PD-L2, CTLA-4, OX40, C137 inhibitors, etc.) acting on T cell costimulation or checkpoint pathway.

(16) patients with CTCAE 5.0 grade ≥ 3 immune-related adverse events (AE) after immunotherapy.

(17) patients receiving glucocorticoid (prednisone \>10mg/ day or equivalent dose of other drugs of the same kind) or other immunosuppressive therapy for some condition within 14 days before the first dose of the drug.

(18) participated in other clinical investigators within 4 weeks before enrollment; (19) a documented history of allergy to study drugs, including enlansubemab, capecitabine, liposome-irinotecan, and any component of the drug; (20) pregnant or lactating female subjects; Patients deemed by the investigator to be ineligible for trial participation.

Where this trial is running

Tianjin, Tianjin Municipality

• Tianjin Medical University Cancer Institute & Hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Study coordinator: Rui Liu, MD

Conditions Advanced Colorectal Cancer