Clinical trial NCT05859373: 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
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-05-16
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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:

  1. 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.
  2. 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.
  3. Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR) ≤ 1.5×ULN (no anticoagulant therapy);
  4. 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:

  1. 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 \[Ta (non-invasive tumors), Tis (carcinoma in situ) and T1 (tumor-invasive basement membrane)\];
  2. Pathological types of mixed small cell and non-small cell lung cancer components；
  3. Patients with known EGFR/ALK mutations
  4. There was Therapeutic toxicity (≥ CTC AE grade 2 infection)
  5. Have a history of idiopathic pulmonary fibrosis, organized pneumonia, drug-induced pneumonia, or idiopathic pneumonia
  6. Subjects who have received major surgical treatment or obvious traumatic injury within 4 weeks prior to initial administration
* Tumor related symptoms and treatment

  1. Received Antitumor traditional Chinese medicine treatment within 2 weeks before the start of research treatment；
  2. Previously received other PD-1/PD-L1/CTLA-4 antibody treatments or immunotherapy;
  3. Uncontrolled pleural effusion, pericardial effusion, or ascites that still require repeated drainage;
* Research treatment related:

  1. Subjects who have received the vaccine within 4 weeks prior to the first dose, or is planning to be vaccinated during the study period
  2. Individuals with a previous history of severe allergies to macromolecular drugs or severe hypersensitivity reactions after administration of other monoclonal antibodies
  3. 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.

Primary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: Baseline to 30 days after last administration.
measure: Severity of adverse events (AEs)
timeFrame: Baseline to 30 days after last administration.
measure: Dose-limiting toxicity (DLT)
timeFrame: Up to 28 days.
measure: Recommended phase II dose (RP2D)
timeFrame: Baseline to 30 days after last administration.
measure: Overall response rate (ORR)
timeFrame: Baseline to the disease progression, up to two years.
Secondary outcomes:
measure: Time to reach maximum plasma concentration (Tmax)
timeFrame: 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.
measure: Peak concentration (Cmax)
timeFrame: 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.
measure: Terminal half-life (t1/2)
timeFrame: 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.
measure: Area under the plasma concentration-time curve from time zero to time t.
timeFrame: 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.
measure: Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss)
timeFrame: 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.
measure: Minimum steady-state plasma drug concentration during a dosage interval (Cmin,ss)
timeFrame: 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.
measure: Disease control rate (DCR)
timeFrame: Baseline to up to two years.
measure: Duration of Response (DOR)
timeFrame: Baseline to up to two years.
measure: Progression-free survival (PFS) at 12 months.
timeFrame: Up to 12 months.
measure: Progression-free survival at 18 months.
timeFrame: Up to 18 months.
measure: Progression-free survival.
timeFrame: Baseline to the disease progression, up to two years.
measure: Overall survival (OS) at 12 months.
timeFrame: Up to 12 months.
measure: Overall survival (OS) at 18 months.
timeFrame: Up to 18 months.
measure: Overall survival (OS)
timeFrame: Baseline to the disease progression, up to two years.
Other outcomes:
Locations:
city: Jinan
country: China
facility: Cancer Hospital Affiliated to Shandong First Medical University
state: Shandong
Study officials:
References: