TQB2223 Injection in Combination With Penpulimab in Patients With Advanced Cancers

Study Overview
=================
Brief Summary
-----------------
TQB2223 is a recombinant, fully humanized antibody that binds lymphocyte activation gene-3 (LAG-3) and blocks the LAG-3/ major histocompatibility complex class II (MHC-II) interaction, thus allowing for increased T-cell proliferation and cytokine production. This is a phase I study to evaluate the safety, tolerability, pharmacokinetics (PK) and effectiveness of TQB2223 injection in combination with Penpulimab in subjects with advanced cancers.

Official Title
-----------------
Phase I Clinical Trial to Evaluate the Tolerability and Pharmacokinetics of TQB2223 Injection Combined With Penpulimab Injection in Subjects With Advanced Cancers

Conditions
-----------------
Advanced Cancer

Intervention / Treatment
-----------------
* Drug: TQB2223 injection+ Penpulimab Injection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study; Male or female patient 18 to 75 years of age, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, and life expectancy ≥3 months; Histologically or cytologically confirmed malignancies; Subjects with advanced malignant tumors who failed standard treatment or lacked effective treatment; Patient has at least one evaluable lesion assessed by RECIST 1.1; The main organs function is well; Male or female patient had no plans to become pregnant and voluntarily take effective contraceptive measures during study period until at least 6 months after the last dose of study drug. Exclusion Criteria: Concurrent secondary malignancy. or other malignancy with no evidence of disease for more than 5 years; History of uncontrolled intercurrent illness; Major surgical procedure, radiotherapy, chemotherapy, or immunotherapy within 4 weeks prior to first dose; Prior treatment targeting LAG-3; Unstable or serious concurrent medical conditions, as assessed by the Investigators, that would substantially increase the risk-benefit ratio of participating in the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

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

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

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TQB2223 injection+ Penpulimab Injection<br>intravenous injection of TQB2223 injection and Penpulimab injection for one times every three weeks, 21 days as a treatment cycle. | Drug: TQB2223 injection+ Penpulimab Injection<br>* TQB2223 is an anti lymphocyte activation gene-3 (LAG-3) antibody. Penpulimab Injection is an anti-PD-1 antibody.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity (DLT) | DLT is defined as toxicities that meet pre-defined severity criteria of Common Terminology Criteria for Adverse Events (CTCAE) v5.0, and assessed as having a suspected relationship to TQB2223 injection, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle (21 days) of treatment. | During the first treatment cycle (21 days). | 
| Maximum tolerated dose (MTD) | MTD was defined as the highest dose at which dose-limiting toxicity (DLT) occurred in less than 33% of patients. | During the first treatment cycle (21 days). | 
| Objective Response Rate (ORR) | Defined as the percentage of Complete Response (CR) plus partial response (PR) assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria and Guidelines for Response Criteria for Use in Trials Testing Immunotherapeutics (iRECIST) for solid tumors, Lugano 2014 criteria and Lymphoma Response to Immunomodulatory therapy Criteria (LYRIC) for lymphoma. | From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of anti-drug antibody (ADA) positive patients | Percentage of ADA positive patients will be calculated to evaluate immunogenicity of TQB2223. | Pre-dose on Cycle 1, 2, 4, 8 . 30 days and 90 days after the last dose. Each cycle is 21 days. | 
| The area under the curve (AUC) | The area under the curve (AUC) of serum concentration of TQB2223 | 5 minutes, 2 hour, 6 hours, 24 hours, 144 hours and 336 hours after dose on cycle 1 and cycle 3. Pre-dose on cycle 2, 4, 5, 6, 7, 8. Each cycle is 21 days. | 
| Peak concentration (Cmax) | Maximum observed concentration (Cmax) of TQB2223 | 5 minutes, 2 hour, 6 hours, 24 hours, 144 hours and 336 hours after dose on cycle 1 and cycle 3. Pre-dose on cycle 2, 4, 5, 6, 7, 8. Each cycle is 21 days. | 
| Terminal half-life (T1/2) | The terminal elimination half-life (t 1/2) is the time that takes for the elimination processes to reduce the plasma concentration of the drug in the body by 50 %. | 5 minutes, 2 hour, 6 hours, 24 hours, 144 hours and 336 hours after dose on cycle 1 and cycle 3. Pre-dose on cycle 2, 4, 5, 6, 7, 8. Each cycle is 21 days. | 
| Receptor occupation (RO) | Receptor occupation (RO) of LAG-3 after administration. | 5 minutes, 2 hour, 6 hours, 24 hours, 144 hours and 336 hours after dose on cycle 1 and cycle 3. Pre-dose on cycle 2, 4, 5, 6, 7, 8. Each cycle is 21 days. | 
| Objective Response Rate (ORR) | Defined as the percentage of Complete Response (CR) plus partial response (PR) assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria and Guidelines for Response Criteria for Use in Trials Testing Immunotherapeutics (iRECIST) for solid tumors, Lugano 2014 criteria and Lymphoma Response to Immunomodulatory therapy Criteria (LYRIC) for lymphoma. | From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100 weeks | 
| Disease control rate (DCR) | Defined as the proportion of subjects with CR, PR, or Stable Disease (SD). | From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100 weeks | 
| Duration of Response (DOR) | Defined as the time from first documented response to documented disease progression or death. | From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100 weeks | 
| Progression-free survival (PFS) | Defined as the time from the first dose of TQB2223 to the first occurrence of disease progression or death from any cause. | From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100 weeks | 
| Overall survival (OS) | Overall survival refers to the time from the first treatment to death from any cause. | From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100 weeks | 
| Number of patients with adverse events (AEs) | Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | From the time of informed consent signed to 28 days after the last dose | 
| Number of patients with serious adverse events (SAEs) | Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | From the time of informed consent signed to 28 days after the last dose |