Neoadjuvant CAPOX Plus Ivonescimab Versus CAPOX for Locally Advanced Colon Cancer

A Prospective, Randomized Phase II Study Evaluating CAPOX Combined with Ivonescimab (a PD-1/VEGF-A Bispecific Antibody) Versus CAPOX Alone As Neoadjuvant Therapy in Patients with Locally Advanced Colon Cancer.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Colon Cancer
• Intervention / Treatment: Drug: Ivonescimab; Drug: Oxaliplatin; Drug: Capecitabine

Detailed Description

This phase II, prospective, randomized controlled trial aims to evaluate the efficacy and safety of combining CAPOX chemotherapy with Ivonescimab, a PD-1/VEGF-A bispecific antibody, compared to neoadjuvant CAPOX therapy alone in patients with high-risk recurrent MSS/pMMR-type colon cancer.

• Study Type: Interventional
• Enrollment (Estimated): 168
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Peirong Ding, MD, Ph D; Phone Number: 00862087343124; Email: dingpr@sysucc.org.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Histologically confirmed locally advanced resectable colon adenocarcinoma (colon cancer located more than 12 cm from the anal verge);
2. 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);
3. No distant metastasis;
4. At least one measurable lesion ;
5. 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);
6. No prior anti-tumor treatment for colorectal cancer;
7. Age ≥18 years and ≤75 years, regardless of gender;
8. ECOG performance status score 0-1;
9. Signed written informed consent before enrollment;
10. Expected survival of more than 12 weeks;
11. Adequate organ and bone marrow function.

Exclusion Criteria:

1. History of allergic diseases, severe drug allergies, or known allergy to large molecular weight protein formulations or Ivonesimab;
2. Cardiopulmonary insufficiency or hepatic and renal insufficiency that cannot tolerate CAPOX chemotherapy, known allergies to oxaliplatin, capecitabine, irinotecan;
3. Presence of distant metastases;
4. Incomplete or complete bowel obstruction; however, patients can be enrolled if the obstruction is relieved by conservative treatment, intestinal stenting, or colostomy;
5. History of significant bleeding tendency or coagulation disorders;

6. Any of the following complications:

   1. Major gastrointestinal hemorrhage, perforation
   2. Symptomatic cardiac disease (including unstable angina, myocardial infarction, and heart failure)
   3. Uncontrolled diabetes and hypertension
   4. Uncontrolled diarrhea (despite adequate treatment, it still interferes with daily activities)
7. 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;
8. History of uncontrolled cardiac symptoms or diseases;
9. Previous history of thyroid dysfunction that cannot be maintained within normal range despite medication;
10. 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;
11. Previous exposure to immunotherapy, including immune checkpoint inhibitors, immune cell therapy, or any treatment targeting tumor immune mechanisms;
12. Previous exposure to systemic bevacizumab or its biosimilars;
13. Active infection or unexplained fever >38.5°C during screening or before the first dose (patients with fever due to tumor, as determined by the investigator, may be eligible);
14. Objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-induced pneumonia, active tuberculosis, or severely impaired lung function;
15. Congenital or acquired immunodeficiency (such as HIV-infected individuals, HIV 1/2 antibody positive);
16. For patients with positive acute or chronic active hepatitis B, HBV DNA testing must be performed. If the HBV DNA copy number ≤2×10^3 copies/mL or ≤400 IU/mL or below the limit of detection, they may enroll. HBsAg (+) patients should receive antiviral therapy throughout the study period to prevent viral reactivation. For patients who are anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV viral load (-), prophylactic antiviral therapy is not required but close monitoring for viral reactivation is necessary;
17. Acute or chronic active hepatitis C (HCV), defined as HCV antibody positive and HCV RNA levels above the limit of detection;
18. Vaccination with live vaccines less than 4 weeks before the start of study medication or likely to occur during the study period;
19. Known history of psychotropic drug abuse, alcoholism, or drug addiction;
20. Pregnant or breastfeeding women, and men and women unwilling to use contraception.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant AK112 combined with chemotherapy; Three cycles of neoadjuvant treatment with CAPOX plus Ivonescimab, followed by radical surgery 4 to 5 weeks after the last oxaliplatin dose.	Drug: Ivonescimab; 20mg/kg Q3W，D1; Other Names: AK112; Drug: Oxaliplatin; Oxaliplatin，130mg/m2，D1，Q3W； Drug: Capecitabine; Capecitabine，1000mg/m2，po，BID，D1-D14，Q3W
Active Comparator: Neoadjuvant chemotherapy; Three cycles of neoadjuvant CAPOX treatment, followed by radical surgery 4 to 5 weeks after the last dose of oxaliplatin.	Drug: Oxaliplatin; Oxaliplatin，130mg/m2，D1，Q3W； Drug: Capecitabine; Capecitabine，1000mg/m2，po，BID，D1-D14，Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MPR rate	In the primary tumor (PT), ≤10% residual viable tumor (RVT).	though 12 weeks neoadjuvant treatment，after surgery completed

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic complete response，pCR	Pathological complete response will be made based on assessment of the surgical specimen at the primary treatment site，the absence of any viable tumor cells in the resected primary tumor specimen and all regional lymph node samples.	though 12 weeks neoadjuvant treatment，after surgery completed
R0 resection rate	Complete resection of the tumor with negative margins, meaning no residual tumor is present microscopically.	after surgery completed，up to 1 month
Disease free survival	Defined as the time from randomization to relapse or death, whichever occurred first	2 years
Adverse event (AE)	The severity of AE and the laboratory findings were graded by the investigators according to Common Terminology Criteria for Adverse Events, version 4. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.	up to 3 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Study Chair: Peirong Ding, MD，phD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): April 28, 2025
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: January 17, 2025
• First Submitted That Met QC Criteria: January 17, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 12, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: CAPOX; neoadjuvent chemotherapy; AK112; Ivonescimab
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Colonic Diseases; Colonic Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Capecitabine; Oxaliplatin
• Other Study ID Numbers: 2025-IIT-0112

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No