Clinical trial NCT06507891: A Clinical 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: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non Small Cell Lung Cancer
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-07-18
Enrollment: 30
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:

* 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;
* 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 Response evaluation criteria in solid tumors (RECIST) 1.1;
* 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: epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (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 presently present within 5 years, except for cured cervical carcinoma in situ and 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 TQ-A3334 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
* 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.

Primary outcomes:
measure: Adverse events (AE)
timeFrame: Baseline up to 21 days
measure: Dose limited toxicity (DLT)
timeFrame: Baseline up to 21 days
measure: Maximum tolerable dose (MTD)
timeFrame: Baseline up to 21 days
Secondary outcomes:
measure: Tmax
timeFrame: 5 minutes, 15 minutes, 0.5 hour, 45 minutes, 1 hour, 1.5 hour, 4 hour, 12 hour, 24 hour, 48 hour, 96 hour, 144 hour after oral administration on day 1 and day 29; 30 minutes before oral administration on day 1, day 8, day 15,day 22 and day 29
measure: Cmax
timeFrame: 5 minutes, 15 minutes, 0.5 hour, 45 minutes, 1 hour, 1.5 hour, 4 hour, 12 hour, 24 hour, 48 hour, 96 hour, 144 hour after oral administration on day 1 and day 29; 30 minutes before oral administration on day 1, day 8, day 15,day 22 and day 29
measure: t1/2
timeFrame: 5 minutes, 15 minutes, 0.5 hour, 45 minutes, 1 hour, 1.5 hour, 4 hour, 12 hour, 24 hour, 48 hour, 96 hour, 144 hour after oral administration on day 1 and day 29; 30 minutes before oral administration on day 1, day 8, day 15,day 22 and day 29
measure: Area under the plasma concentration-time curve (AUC 0-t)
timeFrame: 5 minutes, 15 minutes, 0.5 hour, 45 minutes, 1 hour, 1.5 hour, 4 hour, 12 hour, 24 hour, 48 hour, 96 hour, 144 hour after oral administration on day 1 and day 29; 30 minutes before oral administration on day 1, day 8, day 15,day 22 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: Jingling Hospital
state: Jiangsu
Study officials:
References: