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

NCT06919510 | Not Yet Recruiting Phase 2

• 1 other identifier: AK112-IIT-016
• Study Type: interventional
• Target: 90
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of short-course radiotherapy followed by ivonescimab and chemotherapy in participants with pMMR/MSS locally advanced rectal cancer. Patients were randomly assigned to experimental group A or control group B according to a 1:1 ratio. In group A, patients will receive neoadjuvant short-course radiotherapy followed by ivonescimab and chemotherapy. In group B, patients will receive neoadjuvant short-course radiotherapy followed by chemotherapy. After neoadjuvant treatment, the patients and investigator could choose one of the following treatments:(1) Surgery. The patients will receive surgery within 4-8 weeks after the last dose of capecitabine, and the surgical method is selected by the investigator, (2) Watch and Wait (only for patients with clinical complete response after neoadjuvant therapy).

Conditions

Rectal Adenocarcinoma

Outcome Measures

Primary Outcomes (3)

• Adverse events

  Adverse events and surgical safety

  Through study completion, an average of 6 month

• Complete response rate

  The proportion of CR cases (pCR for those who underwent surgery and cCR for those who didn't receive surgery)

  4 weeks after curative surgery for pCR; 2-4 weeks after the completion of neoadjuvant therapy (last dose of capecitabine) for cCR

• Clinical complete response rate

  The proportion of clinical complete response cases.

  2-4 weeks after the completion of neoadjuvant therapy (last dose of capecitabine)

Secondary Outcomes (7)

• Pathologic complete response

  4 weeks after surgery

• TRG

  4 weeks after surgery

• R0 resection rate

  4 weeks after surgery

• Local recurrence

  3 years after Randomization

• Distant metastasis

  3 years after Randomization

Study Arms (2)

Group A (Short-course radiotherapy followed by ivonescimab and chemotherapy)

EXPERIMENTAL

Subjects will receive short-course radiotherapy of 25Gy/5 fractions, followed by neoadjuvant chemotherapy of CAPOX and ivonescimab. After neoadjuvant treatment, the patients and investigator could choose one of the following treatments:(1) Surgery. The patients will receive surgery within 4-8 weeks after the last dose of capecitabine, and the surgical method is selected by the investigator: (2) Watch and Wait(only for patients with clinical complete response after neoadjuvant therapy).

Drug: lvonescimab; Drug: CAPOX (oxaliplatin/capecitabine); Radiation: radiotherapy; Procedure: Surgery or watch&wait

Group B (Short-course radiotherapy followed by chemotherapy)

ACTIVE COMPARATOR

Subjects will receive short-course radiotherapy of 25Gy/5 Fraction, followed by neoadjuvant chemotherapy of CAPOX .After neoadiuvant treatment, the patients and investigator could choose one of the following treatments:(1) Surgery. The patients will receive surgery within 4-8 weeks after the last dose of capecitabine, and the surgical method is selected by the investigator; (2) Watch and Wait (only for patients with clinical complete response after neoadjuvant therapy).

Drug: CAPOX (oxaliplatin/capecitabine); Radiation: radiotherapy; Procedure: Surgery or watch&wait

Interventions

lvonescimab DRUG

lvonescimab, DS1, D1,q3w, intravenous infusion

Group A (Short-course radiotherapy followed by ivonescimab and chemotherapy)

CAPOX (oxaliplatin/capecitabine) DRUG

Oxaliplatin 130 mg / m2, D1, intravenous infusion, q3w, Capecitabine 1000 mg / m2,twice a day, oral,1-14 days, then rest for 7 days, q3w.

Group A (Short-course radiotherapy followed by ivonescimab and chemotherapy); Group B (Short-course radiotherapy followed by chemotherapy)

radiotherapy RADIATION

5\* 5Gy, once a day, 5Gy each time, for 5 days

Group A (Short-course radiotherapy followed by ivonescimab and chemotherapy); Group B (Short-course radiotherapy followed by chemotherapy)

Surgery or watch&wait PROCEDURE

The surgical method is selected by the investigator. Watch and Wait (only for patients with clinical complete response after neoadjuvant therapy)

Group A (Short-course radiotherapy followed by ivonescimab and chemotherapy); Group B (Short-course radiotherapy followed by chemotherapy)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 75 years;
• ECOG perfommance status of 0 or 1;
• Life expectancy: more than 2 years;
• Histologically proven rectal adenocarcinoma;
• Tumor biopsy immunohistochemistry proven pMMR, positive for four proteins, MLH1, MSH2, MSH6 and PMS2, or MSS determined by gene testing;
• 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;
• Eligible for R0 surgery;
• No prior anti-tumor treatment for rectal cancer,including radiotherapy,chemotherapy, immunotherapy, biologics, small molecule targeted therapy, etc;
• Adequate organ function;
• Males or females with reproductive ability who are willing to use contraception in the trial;

You may not qualify if:

• Any distant metastasis or inoperable disease, regardless clinical stage;
• Previous (within 5 years) or concurrent other malignant tumors, excluding those that have been cured;
• Current presence of gastric intestine obstruction, bleeding or perforation which need emergency surgery;
• Multiple primary rectal cancers;
• Previous pelvic or abdominal radiotherapy;
• Difficulty swallowing;
• Current presence of uncontrolled combined disease;
• Active clinical infections;
• History of severe bleeding tendency or coagulation dysfunction;
• Presence or history of immunodeficiency; positive for HIV antibodies, current long-term use of systemic corticosteroids or other immunosuppressants;
• Subjects with known active tuberculosis (TB); suspected active TB should be excluded by clinical examination, known active syphilis infection;
• Received a live vaccine within 30 days prior to the study, or plan to receive a live vaccine during the study;
• 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;

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Akeso: collaborator

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Oxaliplatin; Capecitabine; Radiotherapy; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: President

Study Record Dates

• First Submitted: April 2, 2025
• First Posted: April 9, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 9, 2025

Record last verified: 2025-04