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

NCT04273815 | Unknown Phase 1

• 1 other identifier: TQA3334-Ⅰ-02
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Adverse events (AE)

  The occurrence of adverse events and serious adverse events.

  Baseline up to 21 days

• Dose limited toxicity (DLT) and Maximum tolerable dose (MTD)

  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).

  Baseline up to 21 days

Secondary Outcomes (8)

• Tmax

  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

  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

  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.

• AUC0-t

  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.

• Overall response rate (ORR)

  up to 96 weeks

Study Arms (2)

TQ-A3334 tablets

EXPERIMENTAL

TQ-A3334 tablets administered orally on day1, 8, 15 in 21-day cycle.

Drug: TQ-A3334

TQ-A3334 tablets + anlotinib capsules

EXPERIMENTAL

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; Drug: Anlotinib

Interventions

TQ-A3334 DRUG

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.

TQ-A3334 tablets; TQ-A3334 tablets + anlotinib capsules

Anlotinib DRUG

Anlotinib is a multi-target receptor tyrosine kinase inhibitor.

TQ-A3334 tablets + anlotinib capsules

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \. 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.

Sponsors & Collaborators

• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: lead

Study Sites (1)

Jinling Hospital

Nanjing, Jiangsu, 210023, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

anlotinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Yong Song, Doctor

CONTACT

025-80860148; yong_song6310@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2020
• First Posted: February 18, 2020
• Study Start: July 6, 2020
• Primary Completion: January 31, 2021
• Study Completion: January 31, 2021
• Last Updated: July 8, 2020

Record last verified: 2020-07

Locations

CN (1)