Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03910127
Recruitment Status : Recruiting
First Posted : April 10, 2019
Last Update Posted : October 30, 2019
Sponsor:
Information provided by (Responsible Party):
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: TQB2450 Drug: Anlotinib Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Cancer(NSCLC)
Actual Study Start Date : June 11, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : June 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TQB2450 + Anlotinib (10 mg)
TQB2450 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)
Drug: TQB2450
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.

Drug: Anlotinib
a multi-target receptor tyrosine kinase inhibitor

Experimental: TQB2450 + Anlotinib (12 mg)
TQB2450 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)
Drug: TQB2450
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.

Drug: Anlotinib
a multi-target receptor tyrosine kinase inhibitor

Placebo Comparator: TQB2450 + Placebo
TQB2450 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)
Drug: TQB2450
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.

Drug: Anlotinib
matching placebo




Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: up to approximately 18 months ]
    PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause.


Secondary Outcome Measures :
  1. Adverse Event (AE): Drug dose adjustment [ Time Frame: up to approximately 18 months ]
    Security Index

  2. Overall response rate (ORR) [ Time Frame: up to approximately 18 months ]
    Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR)

  3. Disease control rate(DCR) [ Time Frame: up to approximately 18 months ]
    Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR) and Stable Disease (SD).

  4. Overall survival (OS) [ Time Frame: up to approximately 24 months ]
    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.

  5. 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). ]
    The Cmax is observed maximum serum concentration, taken directly from the serum concentration-time profile

  6. 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). ]
    The AUC(0-infinity) is area under the serum concentration-time curve from time zero to infinite time.

  7. 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). ]
    Terminal half-life



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03910127


Contacts
Layout table for location contacts
Contact: Baohui Han, Doctor 18930858216 18930858216@164.com

Locations
Layout table for location information
China, Gansu
Gansu Province Tumor Hospital Recruiting
Lanzhou, Gansu, China
Contact: Lei Yang, Doctor         
China, Henan
Henan Province Tumor Hospital Recruiting
Luoyan, Henan, China
Contact: Qiming Wang, Doctor         
Contact: Zhiyong Ma, Doctor         
China, Jilin
Jilin Cancer Hospital Not yet recruiting
Changchun, Jilin, China, 132000
Contact: Ying Chen, Doctor         
Sponsors and Collaborators
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Investigators
Layout table for investigator information
Principal Investigator: Baohui Han, Doctor Shanghai Chest Hospital
Principal Investigator: Kai Li, Doctor Tianjin Cancer Hospital
Layout table for additonal information
Responsible Party: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
ClinicalTrials.gov Identifier: NCT03910127    
Other Study ID Numbers: TQB2450-Ib-01
First Posted: April 10, 2019    Key Record Dates
Last Update Posted: October 30, 2019
Last Verified: January 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms