Neoadjuvant Treatment With mFOLFOXIRI Plus Cadonilimab (AK104) Versus mFOLFOX6 in Locally Advanced Colorectal Cancer

NCT05571644 | Recruiting Phase 2

• 1 other identifier: GIHSYSU-15
• Study Type: interventional
• Target: 143
• Locations: 1 country
• Sites: 1

Brief Summary

Neoadjuvant chemoradiotherapy (CRT) followed by total mesenteric excision (TME) and adjuvant chemotherapy was the standard of treatment for locally advanced rectal cancer (LARC) in the past two decades. The main obstacles for improving survival benefit of LARC was distant metastasis. Recently, total neoadjuvant therapy (TNT) had been recommended as new preferred option for LARC. Induction chemotherapy with FOLFOXIRI followed by CRT or short-course radiotherapy followed by FOLFOX chemotherapy had improved survival benefit for LARC. Neoadjuvant immunotherapy had also been explored in pMMR patients with CRC. In the NICHE trial, neoadjuvant therapy with 2 dose of nivolumab and 1 dose of ipilimumab led to 29% of pathological response and 13% of pCR. Cadonilimab (AK104) was a PD-1/CTLA-4 bi-specific antibody. Here, we tried to explore the efficacy of Neoadjuvant Treatment With mFOLFOXIRI with or without Cadonilimab (AK104) Versus mFOLFOX6 in LARC.

Conditions

Colorectal Cancer

Keywords

Neoadjuvant therapy; mFOLFOXIRI; Cadonilimab (AK104); mFOLFOX6

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR) rates

  Proportion of patients experiencing a pCR to preoperative treatment in each group

  1 year

Secondary Outcomes (3)

• Major pathological response rates

  1 year

• Disease-free survival (DFS)

  3 years

• Local recurrence rate

  3 years

Study Arms (4)

mFOLFOXIRI+Cadonilimab

EXPERIMENTAL

Patients will receive neoadjuvant treatment with mFOLFOXIRI plus cadonilimab for 6 cycles before surgey

Drug: mFOLFOXIRI + Cadonilimab

mFOLFOX6

ACTIVE COMPARATOR

Patients will receive neoadjuvant mFOLFOX6 chemotherapy every two weeks for 6 cycles before surgery.

Drug: mFOLFOX6

mFOLFOXIRI

ACTIVE COMPARATOR

Patients will receive neoadjuvant mFOLFOXIRI chemotherapy every two weeks for 6 cycles before surgery.

Drug: mFOLFOXIRI

mFOLFOXIRI+AK104+fruquintinib

OTHER

Therapeutic Exploratory：Patients will receive neoadjuvant treatment with mFOLFOXIRI plus cadonilimab for 6 cycles and fruquintinib (3mg Qd, D1-21, Q4W for 3 months) before surgey

Drug: mFOLFOXIRI+AK104+fruquintinib

Interventions

mFOLFOXIRI + Cadonilimab DRUG

Cadonilimab（AK104）6mg/kg, intravenous d for 60 minutes, followed by mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) every 2 weeks for 6 cycles before surgery

Also known as: Oxaliplatin, Irinotecan, 5-Fluorouracil, Leucovorin, Cadonilimab (AK104)

mFOLFOXIRI+Cadonilimab

mFOLFOX6 DRUG

mFOLFOX6 (oxaliplatin 85 mg/m2, and folinic acid 400 mg/m2 followed by bolus 5-fluorouracil 400 mg/m2 and 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) every 2 weeks for 6 cycels before surgery

Also known as: Oxaliplatin, 5-Fluorouracil, Leucovorin

mFOLFOX6

mFOLFOXIRI DRUG

mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) every 2 weeks for 6 cycles before surgery

Also known as: Oxaliplatin, Irinotecan, 5-Fluorouracil

mFOLFOXIRI

mFOLFOXIRI+AK104+fruquintinib DRUG

Cadonilimab（AK104）6mg/kg, intravenous d for 60 minutes, followed by mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) every 2 weeks for 6 cycles, and fruquintinib (3mg Qd, D1-21, Q4W for 3 months) before surgery

mFOLFOXIRI+AK104+fruquintinib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-70;
• Colorectal adenocarcinoma with definite histological evidence;
• ECOG Performance status score is 0-1
• Colon cancer was evaluated as T3\>5mm or T4 by contrast-enhanced CT examination of the chest, abdomen and pelvis, and distant displacement was excluded; Rectal cancer was graded as T3-4 and/or N+ by pelvic contrast-enhanced MRI examination, and the lower margin of the tumor was less than 12cm away from the anal margin. Distant metastasis was excluded by chest, abdomen and pelvis CT.
• The primary rectal tumor was assessed as complete resections by a multidisciplinary collaboration group on colorectal cancer, including at least 2 gastrointestinal surgeons and 1 radiologist;
• No previous systemic antitumor therapy for colorectal cancer, including cytotoxic drugs, immunotherapy, molecular targeted therapy, etc.;
• Adequate organ function based on the following laboratory test values obtained within 7 days prior to treatment:
• Hemoglobin ≥90g/L, neutrophil count ≥1.5×109/L, platelet count ≥75×109/L, serum total bilirubin ≤1.5× upper limit of normal value (UNL), aspartate transferase ≤2×UNL, alanine transferase ≤3×UNL, serum creatinine ≤1.5×UNL;
• Willing and able to comply with research protocols and visit plans.

You may not qualify if:

• The patient was complicated with obstruction, active bleeding, or perforation and required emergency surgery or stent placement;
• Active, known or suspected autoimmune diseases (except type I diabetes, residual hypothyroidism requiring only hormone replacement due to autoimmune conditions, or autoimmune diseases that are not expected to recur in the absence of external triggers);
• Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), untreated active hepatitis (hepatitis B, defined as HBV-DNA ≥ 500 IU/ml; Hepatitis C, defined as HCV-RNA above the detection limit of the assay) or co-infection with hepatitis B and C;
• Known allergy to the treatment drug or allergy or intolerance to its ingredients;
• Major surgery or severe trauma, such as laparotomy, thoracotomy, laparoscopic organ resection, etc. within the previous 4 weeks (the surgical incision should be completely healed before enrollment);
• Existing or coexisting other active malignancies (except those that have been treated with curative therapy and remain disease-free for more than 5 years or carcinoma in situ that can be cured by adequate treatment);
• Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody and anti-cytotoxic T-lymphocyte-associated protein 4 (Cytotoxic T-lymphocyte-associated protein 4) antibody. Ctla-4) antibodies or other drugs/antibodies that act on T-cell costimulatory or checkpoint pathways;
• Had active coronary artery disease, severe/unstable angina pectoris or newly diagnosed angina pectoris or myocardial infarction within 6 months prior to study enrollment; Thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism, deep vein thrombosis, occurred within the previous 6 months;
• The New York Heart Association (NYHA) class II or higher congestive Heart failure (see Appendix 3);
• Presence of active inflammatory bowel disease or other colorectal disease leading to chronic diarrhea;
• The presence of any toxicity (Common Terminology Criteria for Adverse Events, CTCAE) (version 5.0) grade 1 or above (except anemia, alopecia, and skin pigmentation) caused by previous treatment that has not subsided;
• Previous or current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, severe impairment of pulmonary function and other lung diseases;
• Active tuberculosis (TB), receiving anti-TB therapy or receiving anti-TB therapy within 1 year before the first dose;
• Persons with known syphilis infection requiring treatment;
• Had used immunosuppressive drugs within 4 weeks before the first dose, Does not include the nasal spray, inhalation, or other ways of topical corticosteroids or physiological doses of systemic corticosteroids (i.e., no more than 10 mg/day prednisone or other equivalent dose glucocorticoids), allows for prevention of allergic reactions, or treatment of diseases such as asthma, chronic obstructive pulmonary disease of breathing difficulties for the temporary use of glucocorticoid;

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Gastrointestinal Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510655, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Oxaliplatin; Irinotecan; Fluorouracil; Leucovorin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Yanhong Deng, Ph.D

  Sixth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yanhong Deng, Ph.D

CONTACT

00862013925106525; dengyanh@mail.sysu.edu.cn

Jianwei Zhang, Ph.D

CONTACT

00862013480216906; zhangjw25@mail.sysu.edu.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: Director of Medical Oncology, Clinical Professor

Study Record Dates

• First Submitted: October 6, 2022
• First Posted: October 7, 2022
• Study Start: July 10, 2023
• Primary Completion: December 31, 2025
• Study Completion (Estimated): August 15, 2027
• Last Updated: July 23, 2025

Record last verified: 2025-07

Locations

CN (1)