ABOD2011 in Patients With Advanced Solid Tumors Progressed After Standard Systemic Therapy

Study Overview
=================
Brief Summary
-----------------
Based on the activation and regulation of immune system by cytokines, mRNA encoding cytokines has become one of the important directions of mRNA tumor drug development. This product (ABOD2011) is a new generation mRNA product for intratumoral injection. The primary objective of this study is to assess the safety and tolerability, of ABOD2011 in patients with advanced solid tumors that progressed after standard systemic therapy.

Official Title
-----------------
An Open-blind Dose Escalation Study to Assess the Safety, Tolerability, and Preliminary Efficacy of ABOD2011 in Patients With Advanced Solid Tumors Progressed After Standard Systemic Therapy

Conditions
-----------------
Patients With Advanced Solid Tumors

Intervention / Treatment
-----------------
* Biological: human single chain IL-12 mRNA-single dose
* Biological: human single chain IL-12 mRNA-multiple dose


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years and older. Understand and voluntarily sign the informed consent form (ICF). Histopathologically confirmed recurrent or metastatic solid tumors. Failure of prior systemic standard of care, or intolerance to severe toxicity, or lack of standard of care. Presence of at least one measurable lesion as assessed by RECIST Version 1.1. At least one superficial or deep lesion for intratumoral administration and biopsy. Sufficient organ functions. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1. Weight > 30 kg. Expected survival longer than 12 weeks. Evidence of menopause in female patients, or for women of childbearing potential: negative for urine or blood pregnancy. Exclusion Criteria: Any systemic anti-tumor therapy, within 28 days prior to the first dose. Radiotherapy within 14 days prior to first dose. Use of immunosuppressants. Major surgery within 28 days. Inadequately controlled diseases. Active autoimmune and inflammatory diseases. Clinically symptomatic central nervous system tumors or metastases. Toxicity of prior anti-tumor therapy is still NCI-CTCAE ≥ 2. Other malignancies within the previous 5 years with the exception of cured basal cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the breast, and carcinoma in situ of the cervix. Active infections. Other conditions that may increase the risk associated with the study drug, or affect the study compliance, etc., which, in the opinion of the investigator, are not suitable for participation in the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Human single chain IL-12 mRNA-single dose<br>Human single chain IL-12 mRNA-single dose | Biological: human single chain IL-12 mRNA-single dose<br>* human single chain IL-12 mRNA administered as specified in the treatment arm with injection once only<br>|
| Experimental: Human single chain IL-12 mRNA-multiple dose<br>Human single chain IL-12 mRNA-multiple dose | Biological: human single chain IL-12 mRNA-multiple dose<br>* human single chain IL-12 mRNA administered as specified in the treatment arm with injection once per week for 3 weeks<br>|

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 Experiencing dose-limiting toxicities (DLTs) | From first dose to Day 28 | 
| Number of Participants Experiencing Adverse Events (AEs) | Number of Participants Experiencing Adverse Events (AEs) | From signed ICF until the date of last visit or start new antitumor therapy, whichever comes first, assessed up to 36 months | 
| Number of Participants Experiencing Severe Adverse Events (SAEs) | Number of Participants Experiencing Severe Adverse Events (SAEs) | From signed ICF until the date of last visit or start new antitumor therapy, whichever came first, assessed up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Overall Response Rate (ORR) | Up to 36 months | 
| Disease Control Rate(DCR) | Disease Control Rate(DCR) | Up to 36 months | 
| Duration of Response (DOR) | Duration of Response (DOR) | Up to 36 months | 
| Progression-Free Survival (PFS) | Progression-Free Survival (PFS) | Up to 36 months | 
| Overall Survival | Overall Survival | Up to 36 months | 
| Maximum observed concentration (Cmax) of ABOD2011 | Maximum observed concentration (Cmax) of ABOD2011 | From first dose of ABOD2011 through to 28 days after last dose of investigational product | 
| Area under the concentration-time curve (AUC) of ABOD2011 | Area under the concentration-time curve (AUC) of ABOD2011 | From first dose of ABOD2011 through to 28 days after last dose of investigational product | 
| Maximum observed concentration (Cmax) of IL-12 | Maximum observed concentration (Cmax) of IL-12 | From first dose of ABOD2011 through to 28 days after last dose of investigational product | 
| Area under the concentration-time curve (AUC) of IL-12 | Area under the concentration-time curve (AUC) of IL-12 | From first dose of ABOD2011 through to 28 days after last dose of investigational product. | 
| Plasma concentration of IFN gamma | Plasma concentration of IFN gamma | From first dose of ABOD2011 through to 28 days after last dose of investigational product. |