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

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

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.

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.