A Phase ll Study of Neoadjuvant Short-course Radiotherapy Followed by Ivonescimab and Chemotherapy in pMMR/MSS Locally Advanced Rectal Cancer

Launched by SUN YAT-SEN UNIVERSITY · Apr 2, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for patients with locally advanced rectal cancer, specifically those with certain tumor characteristics known as pMMR/MSS. The aim is to see how effective and safe a combination of short-course radiotherapy, a medication called ivonescimab, and chemotherapy is compared to short-course radiotherapy followed by chemotherapy alone. Patients will be randomly assigned to one of two groups: one group will receive the combination treatment, while the other will only receive the standard chemotherapy after radiation. After this initial treatment, patients will have the option of undergoing surgery or, if their cancer has responded well, they may choose to "watch and wait" instead of having surgery.

To be eligible for this trial, participants need to be between 18 and 75 years old and have a confirmed diagnosis of rectal adenocarcinoma. They should have a good performance status, meaning they are relatively healthy and can carry out daily activities. Importantly, they should not have received previous treatments for their cancer and must have tumors at a specific stage according to imaging tests. The trial is not yet recruiting participants, but it aims to provide valuable information about a potential new treatment option for patients facing this type of cancer.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Age between 18 and 75 years;
• • 2. ECOG perfommance status of 0 or 1;
• • 3. Life expectancy: more than 2 years;
• • 4. Histologically proven rectal adenocarcinoma;
• • 5. Tumor biopsy immunohistochemistry proven pMMR, positive for four proteins, MLH1, MSH2, MSH6 and PMS2, or MSS determined by gene testing;
• • 6. According to the 8th Edition of the AJCC Staging Manual, clinical stage cT3-4NanyM0 or cTxN+M0 of II-III rectal cancer was determined by Magnetic resonance imaging (MRI)±transrectal ultrasonography/ ultrasound endoscopy. Lower edge of the tumor was ≤ 12 cm from the anal verge;
• • 7. Eligible for R0 surgery;
• • 8. No prior anti-tumor treatment for rectal cancer,including radiotherapy,chemotherapy, immunotherapy, biologics, small molecule targeted therapy, etc;
• • 9. Adequate organ function;
• • 10. Males or females with reproductive ability who are willing to use contraception in the trial;
• Exclusion Criteria:
• • 1. Any distant metastasis or inoperable disease, regardless clinical stage;
• • 2. Previous (within 5 years) or concurrent other malignant tumors, excluding those that have been cured;
• • 3. Current presence of gastric intestine obstruction, bleeding or perforation which need emergency surgery;
• • 4. Multiple primary rectal cancers;
• • 5. Previous pelvic or abdominal radiotherapy;
• • 6. Difficulty swallowing;
• • 7. Current presence of uncontrolled combined disease;
• • 8. Active clinical infections;
• • 9. History of severe bleeding tendency or coagulation dysfunction;
• • 10. Presence or history of immunodeficiency; positive for HIV antibodies, current long-term use of systemic corticosteroids or other immunosuppressants;
• • 11. Subjects with known active tuberculosis (TB); suspected active TB should be excluded by clinical examination, known active syphilis infection;
• • 12. Received a live vaccine within 30 days prior to the study, or plan to receive a live vaccine during the study;
• • 13. Local or systemic disease caused by non-malignancy, or disease or symptom secondary to tumor, that can lead to higher medical risk and/or uncertainty in survival;