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

NCT06507891 | Terminated Phase 1

• 1 other identifier: TQ-A3334-I-02
• Study Type: interventional
• Target: 30
• 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 (3)

• Adverse events (AE)

  The occurrence of adverse events and serious adverse events.

  Baseline up to 21 days

• Dose limited toxicity (DLT)

  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.

  Baseline up to 21 days

• Maximum tolerable dose (MTD)

  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

  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

• Cmax

  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

• t1/2

  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

• Area under the plasma concentration-time curve (AUC 0-t)

  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

• Overall response rate (ORR)

  Up to 96 weeks

Study Arms (2)

TQ-A3334 tablets

EXPERIMENTAL

TQ-A3334 tablets administered orally on day 1, 8, 15 in 21-day cycle.

Drug: TQ-A3334 tablets

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 tablets + Anlotinib capsules

Interventions

TQ-A3334 tablets DRUG

TQ-A3334 is a highly efficient and highly selective Toll-like receptor-7 (TLR-7) agonist. TLR-7 can induce the release of a series of pro-inflammatory cytokines, including interferon alpha (IFN-α), Interleukin 12 (IL-12), Tumor Necrosis Factor Alpha (TNF-α), and promote the maturation and antigen presentation of dendritic cells, play an antitumor effect.

TQ-A3334 tablets

TQ-A3334 tablets + Anlotinib capsules 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. Anlotinib hydrochloride is a muti-target 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;
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Jingling Hospital

Nanjing, Jiangsu, 210023, China

Location

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

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: July 11, 2024
• First Posted: July 18, 2024
• Study Start: July 6, 2020
• Primary Completion: August 25, 2023
• Study Completion: June 4, 2024
• Last Updated: July 18, 2024

Record last verified: 2024-07

Locations

CN (1)