A 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.

Study Overview

• Status: Unknown
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: TQ-A3334; Drug: Anlotinib

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210023
      • Recruiting
      • Jinling Hospital
      • Contact: Yong Song, Doctor; Email: yong_song6310@yahoo.com
      • Principal Investigator: Yong Song, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TQ-A3334 tablets; TQ-A3334 tablets administered orally on day1, 8, 15 in 21-day cycle.	Drug: TQ-A3334; 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.
EXPERIMENTAL: 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).	Drug: TQ-A3334; 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.; Drug: Anlotinib; Anlotinib is a multi-target receptor tyrosine kinase inhibitor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AE)	The occurrence of adverse events and serious adverse events.	Baseline up to 21 days
Dose limited toxicity (DLT) and Maximum tolerable dose (MTD)	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).	Baseline up to 21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate（DCR）	Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR) and Stable Disease (SD).	up to 96 weeks
Progression-free survival (PFS)	PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause.	up to 96 weeks
Tmax	To characterize the pharmacokinetics of TQ-A3334 by assessment of time to reach maximum plasma concentration.	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.
Cmax	Cmax is the maximum plasma concentration of TQ-A3334 or metabolite(s).	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.
t1/2	t1/2 is time it takes for the blood concentration of TQ-A3334 or metabolite(s) to drop by half.	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	To characterize the pharmacokinetics of TQ-A3334 by assessment of area under the plasma concentration time curve from zero to infinity.	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.
Overall response rate (ORR)	Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR).	up to 96 weeks
Duration of Response (DOR)	Time from tumor first assessment to CR or PR to first assessment to PD (Progressive Disease) or death from any cause.	up to 96 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 6, 2020
• Primary Completion (ANTICIPATED): January 31, 2021
• Study Completion (ANTICIPATED): January 31, 2021

Study Registration Dates

• First Submitted: February 16, 2020
• First Submitted That Met QC Criteria: February 16, 2020
• First Posted (ACTUAL): February 18, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 8, 2020
• Last Update Submitted That Met QC Criteria: July 6, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: TQA3334-Ⅰ-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No