AK112 and Chemotherapy in First-line Metastatic Colorectal Cancer

A Randomized, Controlled, Multicenter Phase III Clinical Study of AK112 Combined With Chemotherapy Versus Bevacizumab Combined With Chemotherapy in First-line Metastatic Colorectal Cancer

This trial is a Phase III study. The purpose of this study is to evaluate the efficacy and safety of AK112 and chemotherapy versus bevacizumab and chemotherapy for the first-line treatment of metastatic colorectal cancer.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Adenocarcinoma
• Intervention / Treatment: Drug: AK112; Drug: Oxaliplatin; Drug: Irinotecan; Drug: Leucovorin and 5-FU; Drug: Bevacizumab

• Study Type: Interventional
• Enrollment (Estimated): 560
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xufang Yu, MD; Phone Number: +86(0760)89873999; Email: clincialtrails@akesobio.com

Study Locations

• China
  • Guangdong
    • Guanzhou, Guangdong, China
      • Recruiting
      • Sun Yat-Sen University Cancer Center
      • Contact: Ruihua Xu, MD
    • Guanzhou, Guangdong, China, 510000
      • Recruiting
      • The Sixth Hospital,Sun Yat-sen University
      • Contact: Yanhong DENG, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Signed informed consent.
2. Age ≥ 18 years and ≤ 75 years.
3. ECOG status of 0 or 1.
4. Estimated survival ≥ 3 months.
5. Subjects with histologically or cytologically confirmed metastatic colorectal adenocarcinoma.
6. Subjects who are not candidates for radical surgical resection or local therapy and have not received systemic anti-tumor therapy in the recurrent or metastatic setting. Subjects who have received prior neoadjuvant or adjuvant therapy and whose first discovery of recurrence or metastases is ≥ 12 months after the last dose of neoadjuvant or adjuvant therapy are allowed to enroll.
7. At least one measurable disease based on RECIST v1.1.
8. Adequate organ function per protocol-defined criteria.
9. Women of childbearing potential and men with female partners of childbearing potential must agree to use effective contraception during treatment and for at least 180 days following the last dose of study treatment.

Exclusion Criteria:

1. Previous (within 3 years) or concurrent other malignant tumors, excluding those that have been cured.
2. Participating in other interventional study within 4 weeks prior to the first study drug administration.
3. Palliative local treatment for non-target lesions within 2 weeks prior to the first administration; received non-specific immunomodulatory therapy within 2 weeks prior to the first administration.
4. Current presence of uncontrolled combined disease.
5. Active clinical infections.
6. History of severe bleeding tendency or coagulation dysfunction.
7. Subjects with known active tuberculosis (TB); suspected active TB should be excluded by clinical examination, known active syphilis infection.
8. Received a live vaccine within 30 days prior to the study, or plan to receive a live vaccine during the study.
9. Current presence of significant radiographic or clinical manifestations of GI obstruction.
10. Toxicities of prior anticancer therapy have not resolved to ≤ Grade 1 (NCI-CTCAE version 5.0).
11. Pregnant or lactating women.
12. Any condition considered by the investigator to be inappropriate for enrollment.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK112 in combination with FOLFOXIRI; AK112 in combination with FOLFOXIRI (Irinotecan, Oxaliplatin, Leucovorin and 5-FU) for induction treatment. Later, patients will receive maintenance Leucovorin and 5-FU plus AK112.	Drug: AK112; iv, q2w; Drug: Oxaliplatin; iv, q2w; Drug: Irinotecan; iv, q2w; Drug: Leucovorin and 5-FU; iv, q2w
Active Comparator: Bevacizumab in combination with FOLFOXIRI; Bevacizumab in combination with FOLFOXIRI (Irinotecan, Oxaliplatin, Leucovorin and 5-FU) for induction treatment. Later, patients will receive maintenance Leucovorin and 5-FU plus Bevacizumab .	Drug: Oxaliplatin; iv, q2w; Drug: Irinotecan; iv, q2w; Drug: Leucovorin and 5-FU; iv, q2w; Drug: Bevacizumab; iv, q2w

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) assessed by blinded independent central review (BICR)	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first (based on RECIST 1.1 criteria).	Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to approximately 5 years
Progression-free survival (PFS) assessed by investigator	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first (based on RECIST 1.1 criteria).	Up to approximately 3 years
Objective Response Rate (ORR)	ORR is defined as proportion of subjects who have a complete or partial response relative to baseline according to RECIST 1.1 criteria.	Up to approximately 3 years
Duration of Response (DoR)	DoR is defined as the duration from the first documentation of objective response to the first documented disease progression(based on RECIST v1.1 criteria) or death due to any cause, whichever occurs first.	Up to approximately 3 years
Disease control rate (DCR)	DCR is defined as the proportion of subjects with CR, PR, or SD (based on RECIST v1.1 criteria).	Up to approximately 3 years

Collaborators and Investigators

• Sponsor: Akeso

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2025
• Primary Completion (Estimated): January 13, 2027
• Study Completion (Estimated): January 7, 2029

Study Registration Dates

• First Submitted: April 23, 2025
• First Submitted That Met QC Criteria: April 23, 2025
• First Posted (Actual): April 30, 2025

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplasms, Glandular and Epithelial; Colonic Diseases; Carcinoma; Colorectal Neoplasms; Adenocarcinoma; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Camptothecin; Alkaloids; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Oxaliplatin; Bevacizumab; Irinotecan; Fluorouracil; Leucovorin
• Other Study ID Numbers: AK112-312

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No