Clinical trial NCT04273815: A Study to Evaluate the Tolerance, Pharmacokinetics and Efficacy of TQ-A3334 Tablets
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
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: 2020-02-18
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Adverse events (AE)
timeFrame: Baseline up to 21 days
measure: Dose limited toxicity (DLT) and Maximum tolerable dose (MTD)
timeFrame: Baseline up to 21 days
Secondary outcomes:
measure: Tmax
timeFrame: 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.
measure: Cmax
timeFrame: 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.
measure: t1/2
timeFrame: 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.
measure: AUC0-t
timeFrame: 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.
measure: Overall response rate (ORR)
timeFrame: up to 96 weeks
measure: Progression-free survival (PFS)
timeFrame: up to 96 weeks
measure: Duration of Response (DOR)
timeFrame: up to 96 weeks
measure: Disease control rate（DCR）
timeFrame: up to 96 weeks
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Jinling Hospital
state: Jiangsu
Study officials:
References: