Clinical Trials /

Study of TQB2450 Combined With Anlotinib in Patients With Advanced Non-small Cell Lung Cancer(NSCLC)

NCT03910127

Description:

TQB2450 is a humanized monoclonal antibody targeting programmed death ligand-1 (PD-L1), which prevents PD-L1 from binding to PD-1 and B7.1 receptors on T cell surface, restores T cell activity, thus enhancing immune response and has potential to treat various types of tumors.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of TQB2450 Combined With Anlotinib in Patients With Advanced Non-small Cell Lung CancerNSCLC
  • Official Title: A Phase Ib, Multicenter, Randomized Study to Evaluate the Pharmacokinetics, Efficacy and Safety of TQB2450 Combined With or Without Anlotinib in Patients With Advanced Non-small Cell Lung CancerNSCLC

Clinical Trial IDs

  • ORG STUDY ID: TQB2450-Ib-01
  • NCT ID: NCT03910127

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
TQB2450TQB2450 + Anlotinib (10 mg)
AnlotinibTQB2450 + Anlotinib (10 mg)
AnlotinibTQB2450 + Placebo

Purpose

TQB2450 is a humanized monoclonal antibody targeting programmed death ligand-1 (PD-L1), which prevents PD-L1 from binding to PD-1 and B7.1 receptors on T cell surface, restores T cell activity, thus enhancing immune response and has potential to treat various types of tumors.

Trial Arms

NameTypeDescriptionInterventions
TQB2450 + Anlotinib (10 mg)ExperimentalTQB2450 1200 mg administered intravenously (IV) on Day 1 of each 21-day cycle plus Anlotinib capsules 10 mg given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21)
  • TQB2450
  • Anlotinib
TQB2450 + Anlotinib (12 mg)ExperimentalTQB2450 1200 mg administered IV on Day 1 of each 21-day cycle plus Anlotinib capsules 12 mg given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21)
  • TQB2450
  • Anlotinib
TQB2450 + PlaceboPlacebo ComparatorTQB2450 1200 mg administered IV on Day 1 of each 21-day cycle plus Placebo for Anlotinib capsules given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21)
  • TQB2450
  • Anlotinib

Eligibility Criteria

        Inclusion Criteria:

        1.18 years and older; Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
        1; Life expectancy ≥ 3 months.

        2. Histologically or cytologically confirmed Epidermal Growth Factor Receptor (EGFR)/
        Anaplastic Lymphoma Kinase (ALK) wild type non-small cell lung cancer.

        3. Advanced patients who had received at least first-line of standard chemotherapy but
        failed or intolerable , with at least one measurable lesion based on RECIST 1.1.

        4. PD-L1-positive tumor status (TPS≥1%) as determined by an immunohistochemistry (IHC)
        assay based on PD-L1 expression on tumor infiltrating immune cells and/or tumor cells
        performed by a central laboratory.

        5.The main organs function are normally, the following criteria are met:

          1. routine blood tests:hemoglobin (Hb)≥90g/L (no blood transfusion and blood products
             within 14 days); absolute neutrophil count (ANC) ≥1.5×109/L; platelets (PLT)
             ≥80×109/L;

          2. Blood biochemical examination: alanine transaminase (ALT) and aspartate
             aminotransferase (AST)≤ 2.5×ULN (when the liver is invaded,≤ 5×ULN);total bilirubin
             (TBIL)≤1.5×ULN (Gilbert syndrome patients,≤ 3×ULN);serum creatinine (Cr) ≤1.5×ULN,or
             calculated creatinine clearance (CrCl) ≥50ml/min; calculated creatinine clearance
             formula:Ccr=(140-age)×weight(kg)/72×Scr(mg/dl)
             Ccr=[(140-age)×weight(kg)]/[0.818×Scr(umol/L) (According to the calculation results ,
             female Patients ×0.85;1 mg/dL = 88.41 umol/ L)

          3. Coagulation function: activated partial thromboplastin time (aPTT) ,international
             normalized ratio (INR) ,prothrombin time (PT) ≤1.5×ULN;

          4. left ventricular ejection fraction (LVEF) measured by the Cardiac echocardiography ≥
             50%.

             6. Male or female subjects should agree to use an adequate method of contraception
             starting with the first dose of study therapy through 6 months after the last dose of
             study (such as intrauterine devices , contraceptives or condoms) ;No pregnant or
             breastfeeding women, and a negative pregnancy test are received within 7 days before
             the randomization.

             7. Understood and signed an informed consent form.

        Exclusion Criteria:

          1. Prior therapy with Anlotinib, anti-programmed cell death (PD)-1, anti-PD-L1 or other
             immunotherapy against PD-1/PD-L1.

          2. Severe hypersensitivity occurs after administration of other monoclonal antibodies.

          3. Diagnosed and/or treated additional malignancy within 5 years prior to randomization
             with the exception of cured basal cell carcinoma of skin and carcinoma in situ of
             cervix.

          4. Has any active autoimmune disease or history of autoimmune disease, such as autoimmune
             hepatitis, interstitial pneumonia, enteritis, vasculitis, nephritis, asthma patients
             who need bronchiectasis for medical intervention; Subjects with the vitiligo without
             systemic treatment, psoriasis, alopecia, well-controlled type I diabetes mellitus,
             hypothyroidism stable on hormone replacement will not be excluded from this study.

          5. Immunosuppressive therapy with immunosuppressive agents or systemic or absorbable
             local hormones (dosage > 10 mg/day prednisone or other therapeutic hormones) is
             required for the purpose of immunosuppression.

          6. Has multiple factors affecting oral medication, such as inability to swallow,
             post-gastrointestinal resection, chronic diarrhea and intestinal obstruction, etc.

          7. Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring
             recurrent drainage procedures.

          8. Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary with
             blood vessels is unclear.

          9. Has any bleeding or bleeding events ≥ grade 3 or with unhealed wounds, ulcerative , or
             fractures within 4 weeks prior to the first administration.

         10. Has uncontrollable symptoms of brain metastases, spinal cord compression, cancerous
             meningitis within 8 weeks before the first-dosing, or brain or leptomeningeal disease
             found by CT or MRI during screening.

         11. Has received chemotherapy, surgery, radiotherapy, the last treatment from the first
             dose less than 4 weeks, or oral targeted drugs for less than 5 half-lives, or oral
             fluorouracil pyridine drugs for less than 14 days, mitomycin C and nitrosourea for
             less than 6 weeks. Patients whose adverse events (except alopecia) caused by previous
             treatment did not recover to ≤ grade 1.

         12. Patients with any serious and/or uncontrollable disease, including :

               1. Has poor blood pressure control, systolic blood pressure ≥ 150 mmHg, diastolic
                  blood pressure ≥ 90 mmHg;

               2. Thrombotic events, ischemic attacks, myocardial infarction, grade 2 congestive
                  heart failure or arrhythmias requiring treatment including QTc ≥ 480ms occurred
                  within 6 months of first administration;

               3. Severe active or uncontrolled infections ≥ grade 2;

               4. Has known clinical history of liver diseases, including viral hepatitis, known
                  carriers of hepatitis B virus (HBV) must exclude active HBV infection, that is,
                  HBV DNA positive > 1 *104 copies/mL or > 2000 IU/mL, known hepatitis C virus
                  infection (HCV) and HCV RNA positive > 1 *103 copies/mL, or other decompensated
                  hepatitis and chronic hepatitis, which require antiviral treatment;

               5. HIV positive;

               6. Poor control of diabetes mellitus, fasting blood-glucose ≥ grade 2;

         13. Has vaccinated with vaccines or attenuated vaccines within 4 weeks prior to first
             administration.

         14. According to the judgement of the researchers, there are other factors that may lead
             to the termination of the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:up to approximately 18 months
Safety Issue:
Description:PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause.

Secondary Outcome Measures

Measure:Adverse Event (AE): Drug dose adjustment
Time Frame:up to approximately 18 months
Safety Issue:
Description:Security Index
Measure:Overall response rate (ORR)
Time Frame:up to approximately 18 months
Safety Issue:
Description:Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR)
Measure:Disease control rate(DCR)
Time Frame:up to approximately 18 months
Safety Issue:
Description:Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR) and Stable Disease (SD).
Measure:Overall survival (OS)
Time Frame:up to approximately 24 months
Safety Issue:
Description:OS defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive.
Measure:Pharmacokinetics (PK): Maximum Concentration (Cmax)
Time Frame:Hour 0 (before infusion), 30 minutes after start of infusion, 0, 2, 6, 10, 24, 72, 168, 336, 504 hours after end of infusion on cycle 1 and cycle 6 (each cycle is 21 days).
Safety Issue:
Description:The Cmax is observed maximum serum concentration, taken directly from the serum concentration-time profile
Measure:Pharmacokinetics (PK): Area Under the Serum Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
Time Frame:Hour 0 (before infusion), 30 minutes after start of infusion, 0, 2, 6, 10, 24, 72, 168, 336, 504 hours after end of infusion on cycle 1 and cycle 6 (each cycle is 21 days).
Safety Issue:
Description:The AUC(0-infinity) is area under the serum concentration-time curve from time zero to infinite time.
Measure:Pharmacokinetics (PK): t1/2
Time Frame:Hour 0 (before infusion), 30 minutes after start of infusion, 0, 2, 6, 10, 24, 72, 168, 336, 504 hours after end of infusion on cycle 1 and cycle 6 (each cycle is 21 days).
Safety Issue:
Description:Terminal half-life

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

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