Neoadjuvant CAPOX Plus Ivonescimab Versus CAPOX for Locally Advanced Colon Cancer

NCT06790212 | Not Yet Recruiting Phase 2

• 1 other identifier: 2025-IIT-0112
• Study Type: interventional
• Target: 168
• Locations: 0 countries
• Sites: N/A

Brief Summary

Neoadjuvant chemotherapy has been validated by several clinical studies to achieve preoperative downstaging and improve survival outcomes in patients with locally advanced colon cancer . Enhancing the efficacy of neoadjuvant treatment further represents a crucial direction for future research. Recognizing the potential of synergistic effects between immunotherapy and anti-angiogenic therapy, the investigators conducted the present randomized study to explore whether Ivonescimab （a PD-1/VEGF bispecific-antibody）combined with neoadjuvant chemotherapy in locally advanced colon cancer could potentially further improve treatment outcomes.

Conditions

Colon Cancer

Keywords

neoadjuvent chemotherapy; CAPOX; AK112; Ivonescimab

Outcome Measures

Primary Outcomes (1)

• MPR rate

  In the primary tumor (PT), ≤10% residual viable tumor (RVT).

  though 12 weeks neoadjuvant treatment，after surgery completed

Secondary Outcomes (4)

• Pathologic complete response，pCR

  though 12 weeks neoadjuvant treatment，after surgery completed

• R0 resection rate

  after surgery completed，up to 1 month

• Disease free survival

  2 years

• Adverse event (AE)

  up to 3 years

Study Arms (2)

Neoadjuvant AK112 combined with chemotherapy

EXPERIMENTAL

Three cycles of neoadjuvant treatment with CAPOX plus Ivonescimab, followed by radical surgery 4 to 5 weeks after the last oxaliplatin dose.

Drug: Ivonescimab; Drug: Oxaliplatin; Drug: Capecitabine

Neoadjuvant chemotherapy

ACTIVE COMPARATOR

Three cycles of neoadjuvant CAPOX treatment, followed by radical surgery 4 to 5 weeks after the last dose of oxaliplatin.

Drug: Oxaliplatin; Drug: Capecitabine

Interventions

Ivonescimab DRUG

20mg/kg Q3W，D1

Also known as: AK112

Neoadjuvant AK112 combined with chemotherapy

Oxaliplatin DRUG

Oxaliplatin，130mg/m2，D1，Q3W；

Neoadjuvant AK112 combined with chemotherapy; Neoadjuvant chemotherapy

Capecitabine DRUG

Capecitabine，1000mg/m2，po，BID，D1-D14，Q3W

Neoadjuvant AK112 combined with chemotherapy; Neoadjuvant 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:

• Histologically confirmed locally advanced resectable colon adenocarcinoma (colon cancer located more than 12 cm from the anal verge);
• Imaging staging is T4, or T3 (with invasion of the muscularis propria ≥5 mm) combined with at least one of the following risk factors: number of metastatic lymph nodes ≥1, extramural vascular invasion (EMVI+), involvement of the mesocolic fascia. (TNM clinical staging (cTNN) according to the 8th edition of AJCC/UICC guidelines);
• No distant metastasis;
• At least one measurable lesion ;
• Immunohistochemical testing of endoscopic biopsy samples by the study center's pathology department confirms diagnosis as pMMR, or genetic testing confirms MSS/MSS-L status (by PCR or NGS method);
• No prior anti-tumor treatment for colorectal cancer;
• Age ≥18 years and ≤75 years, regardless of gender;
• ECOG performance status score 0-1;
• Signed written informed consent before enrollment;
• Expected survival of more than 12 weeks;
• Adequate organ and bone marrow function.

You may not qualify if:

• History of allergic diseases, severe drug allergies, or known allergy to large molecular weight protein formulations or Ivonesimab;
• Cardiopulmonary insufficiency or hepatic and renal insufficiency that cannot tolerate CAPOX chemotherapy, known allergies to oxaliplatin, capecitabine, irinotecan;
• Presence of distant metastases;
• Incomplete or complete bowel obstruction; however, patients can be enrolled if the obstruction is relieved by conservative treatment, intestinal stenting, or colostomy;
• History of significant bleeding tendency or coagulation disorders;
• Any of the following complications:
• Major gastrointestinal hemorrhage, perforation
• Symptomatic cardiac disease (including unstable angina, myocardial infarction, and heart failure)
• Uncontrolled diabetes and hypertension
• Uncontrolled diarrhea (despite adequate treatment, it still interferes with daily activities)
• Patients who are using immunosuppressants, systemic, or absorbable topical steroids for immunosuppressive purposes (dose \>10 mg/day prednisone or equivalent), and continue to use them within 2 weeks before enrollment;
• History of uncontrolled cardiac symptoms or diseases;
• Previous history of thyroid dysfunction that cannot be maintained within normal range despite medication;
• Use of traditional Chinese medicine immune modulators within 2 weeks before official treatment, or received systemic chemotherapy, immunotherapy, biological therapy, or other anti-tumor treatments including traditional Chinese medicine within 4 weeks prior to enrollment;
• Previous exposure to immunotherapy, including immune checkpoint inhibitors, immune cell therapy, or any treatment targeting tumor immune mechanisms;

Sponsors & Collaborators

• Sun Yat-sen University: lead

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Oxaliplatin; Capecitabine

Condition Hierarchy (Ancestors)

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

Study Officials

• Peirong Ding, MD，phD

  Sun Yat-sen University

  STUDY CHAIR

Central Study Contacts

Peirong Ding, MD, Ph D

CONTACT

00862087343124; dingpr@sysucc.org.cn

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: Professor

Study Record Dates

• First Submitted: January 17, 2025
• First Posted: January 23, 2025
• Study Start: April 28, 2025
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: March 17, 2025

Record last verified: 2025-03