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To Evaluate the Efficacy and Safety of TQB3728 Tablets in Sequential Maintenance of TQB2450 Injection Therapy in Patients After Sequential or Concurrent Chemoradiation for Locally Advanced Non-small Cell Lung Cancer.

Primary Purpose

Non-small Cell Lung Cancer

Status
Not yet recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
TQB3728 tablets, TQB2450 injection, sequential or concurrent chemoradiation
TQB3728 tablets, TQB2450 injection, sequential or concurrent chemoradiation
TQB2450 injection, sequential or concurrent chemoradiation
Sponsored by
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Between the ages of 18-75 years (calculated based on the date of signing Informed consent form (ICF) ); male or female; Non resectable stage III non-small cell lung cancer (NSCLC) patients confirmed by histopathological or cytological examination; At least one measurable lesion (based on RECIST 1.1); Has not received any systematic treatment or targeted radiotherapy for locally advanced non-small cell lung cancer; Eastern cooperative oncology group (ECOG) score 0-1; Estimated survival time ≥ 3 months; The main organs function are normally, meeting following criteria: routine blood tests: hemoglobin (HGB) ≥80g/L (no blood transfusion and blood products within 14 days); absolute neutrophil count (ANC) ≥1.5×109/L; platelets (PLT)≥90×10^9/L. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN. Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (ULN);Serum creatinine (CR) ≤ 1.5×ULN or creatinine clearance (CCR) ≥ 60 ml/min. Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR) ≤ 1.5×ULN (no anticoagulant therapy); Cardiac ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ 50%. Female participants should have a negative serum pregnancy test within 7 days prior to study enrollment and must be a non-lactating subject; Participants should agree that contraception must be used during the study period and for 6 months after the end of the study. Exclusion Criteria: Comorbidity and medical history: Have had or currently have other malignant tumors within 2 years. The following two conditions can be enrolled: other malignancies treated with a single surgery; cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors [Ta (non-invasive tumors), Tis (carcinoma in situ) and T1 (tumor-invasive basement membrane)]; Pathological types of mixed small cell and non-small cell lung cancer components; Patients with known EGFR/ALK mutations There was Therapeutic toxicity (≥ CTC AE grade 2 infection) Have a history of idiopathic pulmonary fibrosis, organized pneumonia, drug-induced pneumonia, or idiopathic pneumonia Subjects who have received major surgical treatment or obvious traumatic injury within 4 weeks prior to initial administration Tumor related symptoms and treatment Received Antitumor traditional Chinese medicine treatment within 2 weeks before the start of research treatment; Previously received other PD-1/PD-L1/CTLA-4 antibody treatments or immunotherapy; Uncontrolled pleural effusion, pericardial effusion, or ascites that still require repeated drainage; Research treatment related: Subjects who have received the vaccine within 4 weeks prior to the first dose, or is planning to be vaccinated during the study period Individuals with a previous history of severe allergies to macromolecular drugs or severe hypersensitivity reactions after administration of other monoclonal antibodies Existence of any active autoimmune disease or history of autoimmune disease Subjects who have participated in clinical trials of other anti-tumor drugs within 4 weeks before the first dose According to the judgment of the investigator, subjects with concomitant diseases that seriously endanger the safety of the subjects or affect the completion of the study, or subjects with other reasons which are not suitable for inclusion.

Sites / Locations

  • Cancer Hospital Affiliated to Shandong First Medical University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

TQB3728 tablets+chemoradiation, sequential maintenance with TQB2450 injection

TQB3728 tablets+chemoradiation, sequential maintenance with TQB3728 tablets and TQB2450 injection

Sequential or concurrent chemoradiation, sequential maintenance with TQB2450 injection.

Arm Description

TQB3728 tablets combined with sequential or concurrent chemoradiation, 21 days as a treatment cycle. After 4~6 cycles, sequential maintenance therapy of TQB2450 injection.

TQB3728 tablets combined with sequential or concurrent chemoradiation, 21 days as a treatment cycle. After 4~6 cycles, sequential maintenance with TQB3728 tablets and TQB2450 injection for 4 cycles. Then sequential maintenance with TQB2450 injection monotherapy;

Sequential or concurrent chemoradiation, 21 days as a treatment cycle. After 4~6 cycles, sequential maintenance with TQB2450 injection;

Outcomes

Primary Outcome Measures

Incidence of adverse events (AEs)
All adverse medical events that occur after the subject receives the investigational drug evaluated according to the National Cancer Institute standard for common toxic reactions (NCI-CTC) V5.0.
Severity of adverse events (AEs)
All adverse medical events that occur after the subject receives the investigational drug evaluated according to the National Cancer Institute standard for common toxic reactions (NCI-CTC) V5.0.
Dose-limiting toxicity (DLT)
Subjects within 28 days after treatment appear the following toxicity reaction relate to the drug: grade III or above of non-hematological toxicity, grade IV hematological toxicity, neutropenia associated with fever.
Recommended phase II dose (RP2D)
The RP2D defined as the lower dose level to maximum tolerated dose based on the safety profile.
Overall response rate (ORR)
According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the proportion of subjects whose tumors are evaluated as complete response (CR) and partial response (PR) by subcenter imaging evaluation. It is recorded from the first dose of the drug to disease progression or initiation of a new anticancer treatment.

Secondary Outcome Measures

Time to reach maximum plasma concentration (Tmax)
To characterize the pharmacokinetics of TQB3728 by assessment of time to reach maximum plasma concentration.
Peak concentration (Cmax)
Cmax is the maximum plasma concentration of TQB3728 or metabolite(s).
Terminal half-life (t1/2)
Pharmacokinetics parameters to evaluate the half life of TQB3728.
Area under the plasma concentration-time curve from time zero to time t.
To characterize the pharmacokinetics of TQB3728 by assessment of area under the plasma concentration time curve from zero to specific time or infinity.
Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss)
Cmax,ss is the steady state maximum concentration of TQB3728.
Minimum steady-state plasma drug concentration during a dosage interval (Cmin,ss)
Cmin,ss is the minimum plasma concentration of TQB3728.
Disease control rate (DCR)
Percentage of subjects achieving CR and PR and stable disease (SD).
Duration of Response (DOR)
The period from the subjects first achieving CR or PR to disease progression.
Progression-free survival (PFS) at 12 months.
PFS defined as the time from first dose to the first documented progressive disease (PD) or death from any cause.
Progression-free survival at 18 months.
PFS defined as the time from first dose to the first documented progressive disease (PD) or death from any cause.
Progression-free survival.
PFS defined as the time from first dose to the first documented progressive disease (PD) or death from any cause.
Overall survival (OS) at 12 months.
OS is defined as the time from the first administration to all-cause death.
Overall survival (OS) at 18 months.
OS is defined as the time from the first administration to all-cause death.
Overall survival (OS)
OS is defined as the time from the first administration to all-cause death.

Full Information

First Posted
May 5, 2023
Last Updated
May 5, 2023
Sponsor
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05859373
Brief Title
To Evaluate the Efficacy and Safety of TQB3728 Tablets in Sequential Maintenance of TQB2450 Injection Therapy in Patients After Sequential or Concurrent Chemoradiation for Locally Advanced Non-small Cell Lung Cancer.
Official Title
A Randomized, Open Label, Parallel Controlled, Multicenter Phase Ib/II Clinical Trial to Evaluate the Efficacy and Safety of TQB3728 Tablets in Sequential Maintenance of TQB2450 Injection Therapy in Patients After Sequential or Concurrent Chemoradiation for Locally Advanced Non-small Cell Lung Cancer.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
June 2023 (Anticipated)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
It's a Phase Ib/II clinical trial to evaluate the efficacy and safety of TQB3728 tablets in sequential maintenance TQB2450 injection therapy in patients after sequential or concurrent chemoradiation for locally advanced non-small cell lung cancer. Incidence and severity of adverse events (AEs), the type of dose-limiting toxicity(ies) (DLT[s]) and Recommended phaseII dose(RP2D) were the Phase Ib primary endpoint. Overall response rate (ORR) was the Phase II primary endpoint.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
78 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TQB3728 tablets+chemoradiation, sequential maintenance with TQB2450 injection
Arm Type
Experimental
Arm Description
TQB3728 tablets combined with sequential or concurrent chemoradiation, 21 days as a treatment cycle. After 4~6 cycles, sequential maintenance therapy of TQB2450 injection.
Arm Title
TQB3728 tablets+chemoradiation, sequential maintenance with TQB3728 tablets and TQB2450 injection
Arm Type
Experimental
Arm Description
TQB3728 tablets combined with sequential or concurrent chemoradiation, 21 days as a treatment cycle. After 4~6 cycles, sequential maintenance with TQB3728 tablets and TQB2450 injection for 4 cycles. Then sequential maintenance with TQB2450 injection monotherapy;
Arm Title
Sequential or concurrent chemoradiation, sequential maintenance with TQB2450 injection.
Arm Type
Active Comparator
Arm Description
Sequential or concurrent chemoradiation, 21 days as a treatment cycle. After 4~6 cycles, sequential maintenance with TQB2450 injection;
Intervention Type
Combination Product
Intervention Name(s)
TQB3728 tablets, TQB2450 injection, sequential or concurrent chemoradiation
Intervention Description
TQB3728 is an inhibitor of apoptosis protein. TQB2450 injection is humanized monoclonal antibody to Programmed Cell Death Protein 1 (PD-1).
Intervention Type
Combination Product
Intervention Name(s)
TQB3728 tablets, TQB2450 injection, sequential or concurrent chemoradiation
Intervention Description
TQB3728 is an inhibitor of apoptosis protein. TQB2450 injection is humanized monoclonal antibody to Programmed Cell Death Protein 1 (PD-1).
Intervention Type
Combination Product
Intervention Name(s)
TQB2450 injection, sequential or concurrent chemoradiation
Intervention Description
TQB2450 injection is humanized monoclonal antibody to Programmed Cell Death Protein 1 (PD-1).
Primary Outcome Measure Information:
Title
Incidence of adverse events (AEs)
Description
All adverse medical events that occur after the subject receives the investigational drug evaluated according to the National Cancer Institute standard for common toxic reactions (NCI-CTC) V5.0.
Time Frame
Baseline to 30 days after last administration.
Title
Severity of adverse events (AEs)
Description
All adverse medical events that occur after the subject receives the investigational drug evaluated according to the National Cancer Institute standard for common toxic reactions (NCI-CTC) V5.0.
Time Frame
Baseline to 30 days after last administration.
Title
Dose-limiting toxicity (DLT)
Description
Subjects within 28 days after treatment appear the following toxicity reaction relate to the drug: grade III or above of non-hematological toxicity, grade IV hematological toxicity, neutropenia associated with fever.
Time Frame
Up to 28 days.
Title
Recommended phase II dose (RP2D)
Description
The RP2D defined as the lower dose level to maximum tolerated dose based on the safety profile.
Time Frame
Baseline to 30 days after last administration.
Title
Overall response rate (ORR)
Description
According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the proportion of subjects whose tumors are evaluated as complete response (CR) and partial response (PR) by subcenter imaging evaluation. It is recorded from the first dose of the drug to disease progression or initiation of a new anticancer treatment.
Time Frame
Baseline to the disease progression, up to two years.
Secondary Outcome Measure Information:
Title
Time to reach maximum plasma concentration (Tmax)
Description
To characterize the pharmacokinetics of TQB3728 by assessment of time to reach maximum plasma concentration.
Time Frame
For single dose, pre-dose, 0.5,1, 2, 3, 4, 8, 24 hours after dose; For multiple dose, pre-dose on day 3, day 5, day 7, day 14 and 0.5, 1, 2, 4, 8, 24, 48, 72 hours after dose on day14.
Title
Peak concentration (Cmax)
Description
Cmax is the maximum plasma concentration of TQB3728 or metabolite(s).
Time Frame
For single dose, pre-dose, 0.5,1, 2, 3, 4, 8, 24 hours after dose; For multiple dose, pre-dose on day 3, day 5, day 7, day 14 and 0.5, 1, 2, 4, 8, 24, 48, 72 hours after dose on day14.
Title
Terminal half-life (t1/2)
Description
Pharmacokinetics parameters to evaluate the half life of TQB3728.
Time Frame
For single dose, pre-dose, 0.5,1, 2, 3, 4, 8, 24 hours after dose; For multiple dose, pre-dose on day 3, day 5, day 7, day 14 and 0.5, 1, 2, 4, 8, 24, 48, 72 hours after dose on day14.
Title
Area under the plasma concentration-time curve from time zero to time t.
Description
To characterize the pharmacokinetics of TQB3728 by assessment of area under the plasma concentration time curve from zero to specific time or infinity.
Time Frame
For single dose, pre-dose, 0.5,1, 2, 3, 4, 8, 24 hours after dose; For multiple dose, pre-dose on day 3, day 5, day 7, day 14 and 0.5, 1, 2, 4, 8, 24, 48, 72 hours after dose on day14.
Title
Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss)
Description
Cmax,ss is the steady state maximum concentration of TQB3728.
Time Frame
For single dose, pre-dose, 0.5,1, 2, 3, 4, 8, 24 hours after dose; For multiple dose, pre-dose on day 3, day 5, day 7, day 14 and 0.5, 1, 2, 4, 8, 24, 48, 72 hours after dose on day14.
Title
Minimum steady-state plasma drug concentration during a dosage interval (Cmin,ss)
Description
Cmin,ss is the minimum plasma concentration of TQB3728.
Time Frame
For single dose, pre-dose, 0.5,1, 2, 3, 4, 8, 24 hours after dose; For multiple dose, pre-dose on day 3, day 5, day 7, day 14 and 0.5, 1, 2, 4, 8, 24, 48, 72 hours after dose on day14.
Title
Disease control rate (DCR)
Description
Percentage of subjects achieving CR and PR and stable disease (SD).
Time Frame
Baseline to up to two years.
Title
Duration of Response (DOR)
Description
The period from the subjects first achieving CR or PR to disease progression.
Time Frame
Baseline to up to two years.
Title
Progression-free survival (PFS) at 12 months.
Description
PFS defined as the time from first dose to the first documented progressive disease (PD) or death from any cause.
Time Frame
Up to 12 months.
Title
Progression-free survival at 18 months.
Description
PFS defined as the time from first dose to the first documented progressive disease (PD) or death from any cause.
Time Frame
Up to 18 months.
Title
Progression-free survival.
Description
PFS defined as the time from first dose to the first documented progressive disease (PD) or death from any cause.
Time Frame
Baseline to the disease progression, up to two years.
Title
Overall survival (OS) at 12 months.
Description
OS is defined as the time from the first administration to all-cause death.
Time Frame
Up to 12 months.
Title
Overall survival (OS) at 18 months.
Description
OS is defined as the time from the first administration to all-cause death.
Time Frame
Up to 18 months.
Title
Overall survival (OS)
Description
OS is defined as the time from the first administration to all-cause death.
Time Frame
Baseline to the disease progression, up to two years.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Between the ages of 18-75 years (calculated based on the date of signing Informed consent form (ICF) ); male or female; Non resectable stage III non-small cell lung cancer (NSCLC) patients confirmed by histopathological or cytological examination; At least one measurable lesion (based on RECIST 1.1); Has not received any systematic treatment or targeted radiotherapy for locally advanced non-small cell lung cancer; Eastern cooperative oncology group (ECOG) score 0-1; Estimated survival time ≥ 3 months; The main organs function are normally, meeting following criteria: routine blood tests: hemoglobin (HGB) ≥80g/L (no blood transfusion and blood products within 14 days); absolute neutrophil count (ANC) ≥1.5×109/L; platelets (PLT)≥90×10^9/L. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN. Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (ULN);Serum creatinine (CR) ≤ 1.5×ULN or creatinine clearance (CCR) ≥ 60 ml/min. Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR) ≤ 1.5×ULN (no anticoagulant therapy); Cardiac ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ 50%. Female participants should have a negative serum pregnancy test within 7 days prior to study enrollment and must be a non-lactating subject; Participants should agree that contraception must be used during the study period and for 6 months after the end of the study. Exclusion Criteria: Comorbidity and medical history: Have had or currently have other malignant tumors within 2 years. The following two conditions can be enrolled: other malignancies treated with a single surgery; cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors [Ta (non-invasive tumors), Tis (carcinoma in situ) and T1 (tumor-invasive basement membrane)]; Pathological types of mixed small cell and non-small cell lung cancer components; Patients with known EGFR/ALK mutations There was Therapeutic toxicity (≥ CTC AE grade 2 infection) Have a history of idiopathic pulmonary fibrosis, organized pneumonia, drug-induced pneumonia, or idiopathic pneumonia Subjects who have received major surgical treatment or obvious traumatic injury within 4 weeks prior to initial administration Tumor related symptoms and treatment Received Antitumor traditional Chinese medicine treatment within 2 weeks before the start of research treatment; Previously received other PD-1/PD-L1/CTLA-4 antibody treatments or immunotherapy; Uncontrolled pleural effusion, pericardial effusion, or ascites that still require repeated drainage; Research treatment related: Subjects who have received the vaccine within 4 weeks prior to the first dose, or is planning to be vaccinated during the study period Individuals with a previous history of severe allergies to macromolecular drugs or severe hypersensitivity reactions after administration of other monoclonal antibodies Existence of any active autoimmune disease or history of autoimmune disease Subjects who have participated in clinical trials of other anti-tumor drugs within 4 weeks before the first dose According to the judgment of the investigator, subjects with concomitant diseases that seriously endanger the safety of the subjects or affect the completion of the study, or subjects with other reasons which are not suitable for inclusion.
Facility Information:
Facility Name
Cancer Hospital Affiliated to Shandong First Medical University
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250117
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yuping Sun, Doctor
Phone
+86 13370582181
Email
13370582181@163.com

12. IPD Sharing Statement

Learn more about this trial

To Evaluate the Efficacy and Safety of TQB3728 Tablets in Sequential Maintenance of TQB2450 Injection Therapy in Patients After Sequential or Concurrent Chemoradiation for Locally Advanced Non-small Cell Lung Cancer.

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