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
Trial Snapshot
- Phase
- Phase 1
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Adverse events (AE)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •1.Understood and signed an informed consent form;
- •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;
- •Has received at least two systemic chemotherapy regimens which is failure or intolerance;
- •At least one measurable lesion（ based on RECIST1.1）;
- •The main organs function are normally;
- •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;
- •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
- •Small cell lung cancer;
- •Other malignant tumors that have appeared or are currently present within 5 years, except for cured cervical carcinoma in situ, non-melanoma skin cancer;
- •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;
- •Expect to use any active vaccine against infectious diseases within 28 days before the first administration or during the study period;
- •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;
- •Active autoimmune diseases that require systemic treatment have occurred within 2 years before the first administration;
- •Hypersensitivity to TQB3804 or its excipient;
- •Has uncontrollable symptoms of brain metastases, spinal cord compression, cancerous meningitis;
- •Has unrelieved toxicity reactions ≥ grade 1 due to previous treatment;
- •Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary with blood vessels is unclear;
- •Has thyroid dysfunction that requires drug treatment within 6 months before the first administration;
- •Has multiple factors affecting oral medication; 13.Has any severe acute complications before the first administration;
- •Have participated in other clinical trials within 4 weeks before the first administration;
- •According to the judgement of the researchers, there are other factors that may lead to the termination of the study;
- •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.
Arms & Interventions
TQ-A3334 tablets
TQ-A3334 tablets administered orally on day1, 8, 15 in 21-day cycle.
Intervention: TQ-A3334 (Drug)
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).
Intervention: TQ-A3334 (Drug)
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).
Intervention: Anlotinib (Drug)
Outcomes
Primary Outcomes
Adverse events (AE)
Time Frame: Baseline up to 21 days
The occurrence of adverse events and serious adverse events.
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 Outcomes
- Overall response rate (ORR)(up to 96 weeks)
- 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.)
- Duration of Response (DOR)(up to 96 weeks)
- Disease control rate（DCR）(up to 96 weeks)
- 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.)
- 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.)
- Progression-free survival (PFS)(up to 96 weeks)