A Study of AK112 in Combination With VG2025 in Colorectal Cancer With Liver Metastases

A Phase Ib/II Clinical Study Evaluating the Safety and Efficacy of AK112 in Combination With VG2025 in Patients With Advanced Colorectal Cancer With Liver Metastases

An open-label, multicenter, phase Ib/II study of AK112 in combination with VG2025 for advanced colorectal cancer with liver metastases.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer With Hepatic Metastases
• Intervention / Treatment: Biological: VG2025; Drug: AK112

Detailed Description

This open-label, multicenter, phase Ib/II clinical study aims to evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of AK112 in combination with VG2025, in the treatment of advanced colorectal cancer with liver metastases.

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ting Liu; Phone Number: +86 (0760) 8987 3999; Email: clinicaltrials@akesobio.com
• Study Contact Backup: Name: Tingbo Liang, MD; Phone Number: +86-13486180288; Email: liangtingbo@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital, Zhejiang University School of Medicine，No. 79, Qingchun Road, Shangcheng District, Hangzhou City, Zhejiang Province
      • Contact: Liang Tingbo, MD; Phone Number: +86-13486180288; Email: liangtingbo@zju.edu.cn

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. Histologically or cytologically confirmed unresectable colorectal cancer with liver metastases; adenocarcinoma type
4. Disease progression after first- or second-line standard therapy
5. At least one measurable disease based on RECIST v1.1
6. ECOG status of 0 or 1
7. Estimated life expectancy≥3 months
8. Adequate organ function
9. Patients with fertility are willing to use an adequate method of contraception

Exclusion Criteria:

1. Histologically or cytologically confirmed non-adenocarcinoma or mixed-type tumors with adenocarcinoma component ≤70%
2. Known dMMR or MSI-H
3. Known RAS or BRAF mutations
4. Participation in another clinical trial
5. Systemic anticancer therapy within 4 weeks, small molecule therapy within 2 weeks, antitumor traditional Chinese medicine within 2 weeks before first dose
6. Prior immunotherapy other than anti-PD-(L)1 agents
7. Live attenuated vaccine within 28 days before or during study treatment and 90 days after last dose
8. Active malignancy within the past 3 years
9. Known spinal cord compression, active brain or leptomeningeal metastases.
10. Significant bleeding events requiring transfusion, invasive intervention, or hospitalization within 3 months before first dose
11. Serious infection within 28 days, or systemic anti-infective therapy within 14 days before first dose (except antiviral therapy for hepatitis B/C)
12. Active herpesvirus infection with clinical manifestations
13. Active autoimmune disease
14. Known immunodeficiency
15. Known allergy to study drug or excipients, or history of severe allergic reactions to other vaccines
16. History of allogeneic organ or hematopoietic stem cell transplantation.
17. Clinically significant liver disease
18. Any other situations that are not suitable for inclusion in this study judged by investigator

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A (VG2025+AK112); VG2025 (Recommended Phase II Dose), Intratumoral Injection, Q4W + AK112 (20mg/kg), ivgtt, Q2W.	Biological: VG2025; Recommended Phase II Dose, Intratumoral Injection, Q4W; Drug: AK112; 20mg/kg, ivgtt, Q2W
Experimental: Cohort B (AK112); AK112 (20mg/kg), ivgtt, Q2W	Drug: AK112; 20mg/kg, ivgtt, Q2W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants experiencing dose-limiting toxicities (DLTs)	Number of participants who meet the criteria of dose-limiting toxicities (DLTs) in DLT observation period	From Day 1 to Day 28 after the first tumour vaccine was administrated in safety run-in cohorts
Number of participants with adverse events (AEs) and severity	Number of participants experiencing adverse events (AEs) and severity, graded according to CTCAE v5.0	From ICF up to 30 days after last study treatment
Objective Response Rate (ORR)	Proportion of participants with complete response (CR) or partial response (PR), as assessed by RECIST version 1.1	Time Frame: Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	Time from the date of enrollment until the first documentation of disease progression or death due to any cause, whichever occurs first, as assessed by RECIST version 1.1	Up to 2 years
Disease control rate (DCR)	Proportion of participants with complete response (CR), partial response (PR), or stable disease (SD), as assessed by RECIST version 1.1	Up to 2 years
Duration of response (DoR)	Time from the first documentation of objective response to the first documented disease progression as assessed by RECIST version 1.1 or death due to any cause, whichever occurs first	Up to 2 years
Time to response (TTR)	Time from the start of the treatment to the first objective tumor response observed for patients who achieved complete response (CR) or partial response (PR), as assessed by RECIST version 1.1	Up to 2 years
Overall survival (OS)	Time from the date of enrollment to death from any cause	Up to 2 years
Observed concentrations of AK112	Observed serum concentrations of AK112 at different time points after AK112 administration	Up to 2 years
Number of participants with detectable anti-drug antibodies (ADAs) to AK112	Number of participants who develop detectable anti-drug antibodies (ADAs) to AK112	Up to 2 years

Collaborators and Investigators

• Sponsor: Akeso
• Collaborators: Shanghai Virogin Biotech Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): March 2, 2026
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2028

Study Registration Dates

• First Submitted: December 24, 2025
• First Submitted That Met QC Criteria: January 12, 2026
• First Posted (Actual): January 21, 2026

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: AK112-212

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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