Colorectal Cancer With Hepatic Metastases
Conditions
Brief summary
An open-label, multicenter, phase Ib/II study of AK112 in combination with VG2025 for advanced colorectal cancer with liver metastases.
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.
Interventions
BIOLOGICALVG2025
Recommended Phase II Dose, Intratumoral Injection, Q4W
DRUGAK112
20mg/kg, ivgtt, Q2W
Sponsors
Akeso
Shanghai Virogin Biotech Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants experiencing dose-limiting toxicities (DLTs) | From Day 1 to Day 28 after the first tumour vaccine was administrated in safety run-in cohorts | Number of participants who meet the criteria of dose-limiting toxicities (DLTs) in DLT observation period |
| Number of participants with adverse events (AEs) and severity | From ICF up to 30 days after last study treatment | Number of participants experiencing adverse events (AEs) and severity, graded according to CTCAE v5.0 |
| Objective Response Rate (ORR) | Time Frame: Up to 2 years | Proportion of participants with complete response (CR) or partial response (PR), as assessed by RECIST version 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) | Up to 2 years | 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 |
| Disease control rate (DCR) | Up to 2 years | Proportion of participants with complete response (CR), partial response (PR), or stable disease (SD), as assessed by RECIST version 1.1 |
| Duration of response (DoR) | Up to 2 years | 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 |
| Time to response (TTR) | Up to 2 years | 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 |
| Overall survival (OS) | Up to 2 years | Time from the date of enrollment to death from any cause |
| Observed concentrations of AK112 | Up to 2 years | Observed serum concentrations of AK112 at different time points after AK112 administration |
| Number of participants with detectable anti-drug antibodies (ADAs) to AK112 | Up to 2 years | Number of participants who develop detectable anti-drug antibodies (ADAs) to AK112 |
Countries
China
Contacts
CONTACTTing Liu
CONTACTTingbo Liang, MD
Outcome results
None listed