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A Study to Evaluate the Tolerance, Pharmacokinetics and Efficacy of TQ-A3334 Tablets

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: NCT04273815
Recruitment Status : Recruiting
First Posted : February 18, 2020
Last Update Posted : July 8, 2020
Sponsor:
Information provided by (Responsible Party):
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Brief Summary:
This is a study to evaluate the tolerance, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) of single and multiple oral doses of TQ-A3334 and observe the efficacy of TQ-A3334 in combination with anlotinib capsules in patients with non-small cell lung cancer.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: TQ-A3334 Drug: Anlotinib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib, Open-label, Dose Escalation and Expansion Study to Evaluate the Tolerance , Pharmacokinetics and Effectiveness of TQ-A3334 Tablets in Patients With Advanced Non-small Cell Lung Cancer
Actual Study Start Date : July 6, 2020
Estimated Primary Completion Date : January 31, 2021
Estimated Study Completion Date : January 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TQ-A3334 tablets
TQ-A3334 tablets administered orally on day1, 8, 15 in 21-day cycle.
Drug: TQ-A3334
TQ-A3334 is a highly efficient and highly selective TLR-7 agonist. TLR-7 can induce the release of a series of pro-inflammatory cytokines, including IFN-α (interferon-α), IL-12 (Interleukin 12), TNF-α, and promote the maturation and antigen presentation of dendritic cells, play an antitumor effect.

Experimental: TQ-A3334 tablets + anlotinib capsules
TQ-A3334 tablets administered orally on day1, 8, 15 in 21-day cycle plus 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: TQ-A3334
TQ-A3334 is a highly efficient and highly selective TLR-7 agonist. TLR-7 can induce the release of a series of pro-inflammatory cytokines, including IFN-α (interferon-α), IL-12 (Interleukin 12), TNF-α, and promote the maturation and antigen presentation of dendritic cells, play an antitumor effect.

Drug: Anlotinib
Anlotinib is a multi-target receptor tyrosine kinase inhibitor.




Primary Outcome Measures :
  1. Adverse events (AE) [ Time Frame: Baseline up to 21 days ]
    The occurrence of adverse events and serious adverse events.

  2. Dose limited toxicity (DLT) and Maximum tolerable dose (MTD) [ Time Frame: Baseline up to 21 days ]
    DLT defined as any of the following events occurring during the study related to drugs : (1) ≥grade 3 non-hematologic toxicity; (2)Grade 4 neutropenia, thrombocytopenia, and hemoglobin reduction confirmed by at least 2 tests within 2 days; (3)Grade 3 neutropenia with fever confirmed at least 2 times within 2 days; (4)Immune-related interstitial pneumonia ≥ grade 2 ;. (5)Decreased ventricular ejection fraction ≥ grade 2 ; (6)Retinal vein occlusion (RVO), uveitis ≥ grade 2 ; MTD defined as the highest dose level at which less than or equal to 2 of 6 subjects experience dose limiting toxicity (DLT).


Secondary Outcome Measures :
  1. Tmax [ Time Frame: 5minutes, 15minutes, 0.5hour, 45minutes, 1hour, 1.5hour, 4hour, 12hour, 24hour, 48hour, 96hour, 144hour after oral administration on day 1 and day 29; 30min before oral administration on day 1, day8, day15,day22 and day 29. ]
    To characterize the pharmacokinetics of TQ-A3334 by assessment of time to reach maximum plasma concentration.

  2. Cmax [ Time Frame: 5minutes, 15minutes, 0.5hour, 45minutes, 1hour, 1.5hour, 4hour, 12hour, 24hour, 48hour, 96hour, 144hour after oral administration on day 1 and day 29; 30min before oral administration on day 1, day8, day15,day22 and day 29. ]
    Cmax is the maximum plasma concentration of TQ-A3334 or metabolite(s).

  3. t1/2 [ Time Frame: 5minutes, 15minutes, 0.5hour, 45minutes, 1hour, 1.5hour, 4hour, 12hour, 24hour, 48hour, 96hour, 144hour after oral administration on day 1 and day 29; 30min before oral administration on day 1, day8, day15,day22 and day 29. ]
    t1/2 is time it takes for the blood concentration of TQ-A3334 or metabolite(s) to drop by half.

  4. AUC0-t [ Time Frame: 5minutes, 15minutes, 0.5hour, 45minutes, 1hour, 1.5hour, 4hour, 12hour, 24hour, 48hour, 96hour, 144hour after oral administration on day 1 and day 29; 30min before oral administration on day 1, day8, day15,day22 and day 29. ]
    To characterize the pharmacokinetics of TQ-A3334 by assessment of area under the plasma concentration time curve from zero to infinity.

  5. Overall response rate (ORR) [ Time Frame: up to 96 weeks ]
    Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR).

  6. Progression-free survival (PFS) [ Time Frame: up to 96 weeks ]
    PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause.

  7. Duration of Response (DOR) [ Time Frame: up to 96 weeks ]
    Time from tumor first assessment to CR or PR to first assessment to PD (Progressive Disease) or death from any cause.

  8. Disease control rate(DCR) [ Time Frame: up to 96 weeks ]
    Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR) and Stable Disease (SD).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1.Understood and signed an informed consent form; 2. 18 years old and older; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1; life expectancy ≥12 weeks; 3.Histologically confirmed advanced non-small cell lung cancer; 4. Has received at least two systemic chemotherapy regimens which is failure or intolerance; 5. At least one measurable lesion( based on RECIST1.1); 6. The main organs function are normally; 7. 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; 8. In addition to the above criteria, the extended research phase must meet the following criteria: EGFR and ALK are negative; or patients with positive test results of EGFR and ALK are resistant or intolerant after receiving the targeted drug treatment.

Exclusion Criteria:

  • 1. Small cell lung cancer; 2. Other malignant tumors that have appeared or are currently present within 5 years, except for cured cervical carcinoma in situ, non-melanoma skin cancer; 3. 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; 4. Expect to use any active vaccine against infectious diseases within 28 days before the first administration or during the study period; 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, and is still in use for 2 weeks after the first administration; 6. Active autoimmune diseases that require systemic treatment have occurred within 2 years before the first administration; 7. Hypersensitivity to TQB3804 or its excipient; 8. Has uncontrollable symptoms of brain metastases, spinal cord compression, cancerous meningitis; 9. Has unrelieved toxicity reactions ≥ grade 1 due to previous treatment; 10. Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary with blood vessels is unclear; 11. Has thyroid dysfunction that requires drug treatment within 6 months before the first administration; 12. Has multiple factors affecting oral medication; 13.Has any severe acute complications before the first administration; 14. Have participated in other clinical trials within 4 weeks before the first administration; 15. According to the judgement of the researchers, there are other factors that may lead to the termination of the study; 16. In addition to the above criteria, the extended research phase must meet the following criteria: 1) Pathologically diagnosed as central, hollow lung squamous cell carcinoma, or non-small cell lung cancer with hemoptysis ; 2) EGFR and ALK are positive untreated with relevant targeted drugs; 3) Has received anlotinib hydrochloride capsules.

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): NCT04273815


Contacts
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Contact: Yong Song, Doctor 025-80860148 yong_song6310@yahoo.com

Locations
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China, Jiangsu
Jinling Hospital Recruiting
Nanjing, Jiangsu, China, 210023
Contact: Yong Song, Doctor       yong_song6310@yahoo.com   
Principal Investigator: Yong Song, Doctor         
Sponsors and Collaborators
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
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Responsible Party: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
ClinicalTrials.gov Identifier: NCT04273815    
Other Study ID Numbers: TQA3334-Ⅰ-02
First Posted: February 18, 2020    Key Record Dates
Last Update Posted: July 8, 2020
Last Verified: July 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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