TQ-B3525 Tablets Combined With Osimertinib Mesylate Tablets in the Treatment of Advanced Non-Small Cell Lung Cancer

NCT05284994 | Unknown Phase 1

• 1 other identifier: TQ-B3525-Ib/II -01
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 9

Brief Summary

TQ-B3525 tablet is a new α/δ dual inhibitor phosphatidylinositol 3-kinase inhibitor developed by Chia Tai Tianqing pharmaceutical Group Co., Ltd. It can overcome the drug resistance problem caused by the up-regulation of phosphatidylinositol 3-kinase α subunit activity caused by the single inhibition of phosphatidylinositol 3-kinase δ subunit. This study is a single-arm, open-label, multi-cohort, multi-center clinical study of the safety and efficacy of TQ-B3525 tablets combined with osimertinib in subjects with advanced non-small cell lung cancer, aiming to evaluate TQ-B3525 tablets combined with osimertinib, the safety, tolerability, and efficacy of the treatment of patients with advanced non-small cell lung cancer who have failed epidermal growth factor receptor inhibitor therapy, while exploring the efficacy, resistance mechanism, and safety in the dose escalation phase biomarkers.

Conditions

Nonsmall-cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity (DLT)

  Some major toxic and side effects of drugs are the main reasons for restricting the continued increase in the dose of chemotherapeutic drugs. These toxic and side effects are the dose-limiting toxicity of chemotherapeutic drugs.

  Baseline time to increase chemotherapy drug dose to toxicity intolerance, up to 5 weeks.

• Objective response rate (ORR)

  Objective response rate refers to the proportion of patients whose tumor shrinkage reaches a certain amount and maintains it for a certain period of time, including complete response (CR)+ partial response (PR) cases.

  From date of first medication until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.

Secondary Outcomes (4)

• Progression-Free-Survival (PFS)

  From date of first medication until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.

• Disease Control Rate (DCR)

  From date of first medication until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.

• Overall Survival (OS)

  From date of first medication until the date of death from any cause，an average of 5 years.

• Duration of disease remission

  Tumors were first assessed as complete response (CR) or partial response (PR) from the date of disease progression or death, whichever occurred first. Through study completion, an average of 1 year.

Study Arms (1)

TQ-B3525 Tablets + Osimertinib Mesylate Tablets.

OTHER

TQ-B3525 tablets combined with osimertinib mesylate tablets, 30 days as a treatment cycle.

Drug: TQ-B3525 Tablets, Osimertinib Mesylate Tablets

Interventions

TQ-B3525 Tablets, Osimertinib Mesylate Tablets DRUG

TQ-B3525 is a novel α/δ dual inhibitor PI3K kinase inhibitor. Osimertinib mesylate is a third-generation epidermal growth factor receptor inhibitor.

TQ-B3525 Tablets + Osimertinib Mesylate Tablets.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 75 years old, and gender is not limited.
• The eastern cooperative oncology group（ECOG）score is 0 to 1, and the expected survival time is greater than or equal to 12 weeks.
• Subjects with histologically or cytologically confirmed non-small cell lung cancer (NSCLC) and stage IIIB-IV (according to the 8th edition of the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer Classification).
• The enrollment requirements for the dose escalation phase are as follows:
• Patients who have failed previous standard therapy, including disease progression or toxicity intolerance, or who are clinically unsuitable or unacceptable, or who refuse to receive standard therapy.
• The test report can reflect the presence of epidermal growth factor receptor (EGFR) sensitive mutations when the subjects were enrolled in this trial.
• Requirements for meeting the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment failure criteria:
• Subjects without T790M mutation after receiving first- or second-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment resistance in the past; or subjects who have previously received third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment resistance.
• According to the definition of response evaluation criteria in solid tumors Recist version 1.1 (Recist 1.1) criteria, disease progression occurs after continuous epidermal growth factor receptor- -tyrosine kinase inhibitor treatment for at least 1 month.
• No other systemic therapy between discontinuation of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) and initiation of new therapy.
• The enrollment requirements for Cohort 1 in the dose expansion phase are as follows:
• failure of previous standard therapy, including disease progression or toxicity intolerance, or clinical inappropriateness/inability to accept/refusal to receive standard therapy.
• There is a sensitive epidermal growth factor receptor（EGFR） mutation, and previous reports have confirmed that it is accompanied by a gene abnormality in the PI3K signaling pathway.
• Requirements for meeting the epidermal growth factor receptor-tyrosine kinase inhibitor（EGFR-TKI）treatment failure criteria:
• Subjects without T790M mutation after receiving first- or second-generation epidermal growth factor receptor-tyrosine kinase inhibitor（EGFR-TKI） treatment resistance in the past; or subjects who have previously received third-generation epidermal growth factor receptor-tyrosine kinase inhibitor（EGFR-TKI）treatment resistance.

You may not qualify if:

• There are contraindications to Osimertinib Mesylate Tablets administration.
• Other malignant tumors that have occurred or are currently at the same time within 3 years, except for cured cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumor.
• The subject has received PI3K inhibitor treatment in the past.
• Subjects who have received other systemic anti-tumor drugs within 3 weeks before the first dose, or who are still within the in 5 half-life period of the drug.
• Received any major surgical treatment within 4 weeks before the first dosage.
• Received any previous radiotherapy for curative purposes within 2 weeks before the first drug.
• Unrelieved toxic reactions higher than common terminology criteria for adverse events （CTC AE）grade 1 due to any previous treatment, excluding alopecia.
• The subjects had active serious viral, or bacterial, or fungal infections within 4 weeks before the first administration.
• One of the following conditions of grade II or above occurred within 6 months before the first medication: myocardial infarction, severe or unstable angina pectoris, coronary or peripheral artery bypass grafting, cerebrovascular accident, including transient cerebral ischemia attack, as well as deep vein thrombosis or pulmonary embolism.
• Current uncontrolled congestive heart failure.
• Currently there is persistent arrhythmia greater than or equal to grade II, any degree of uncontrolled atrial fibrillation or QTc interval greater than 480 ms.
• Subjects with unsatisfactory blood pressure control, that is, subjects with systolic blood pressure greater than or equal to 150 mmHg and diastolic blood pressure greater than or equal to 100 mmHg.
• Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage.
• Type I and type II diabetes, in addition to only taking exercise and diet control, or only needing a single oral hypoglycemic drug to stably control blood sugar, and fasting blood sugar less than 7.0 mmol/L and glycosylated hemoglobin (HbA1c) less than 7.0 during the screening period % of subjects with type II diabetes.
• Presence of interstitial lung disease, severely impaired lung function, severe pulmonary fibrosis, radiation pneumonitis, history of drug-induced lung disease, and evidence of active pulmonary inflammation on chest computed tomography (CT) findings during screening.

Sponsors & Collaborators

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

Study Sites (9)

Sun-Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Sun Yat-Sen Memorial Hospital

Guangzhou, Guangdong, 510120, China

RECRUITING

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510120, China

RECRUITING

Southern Hospital of Southern Medical University

Guangzhou, Guangdong, 510515, China

RECRUITING

The First Affiliated Hospital of Guangdong Pharmaceutical University

Guangzhou, Guangdong, 510699, China

RECRUITING

The Second People's Hospital of Guangdong Province

Guanzhou, Guangdong, 510310, China

RECRUITING

Jiangmen Central Hospital

Jiangmen, Guangdong, 529099, China

RECRUITING

Meizhou People's Hospital

Meizhou, Guangdong, 514001, China

RECRUITING

Affiliated Hospital Of Guangdong Medical University

Zhanjiang, Guangdong, 510180, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Li Zhang, Doctor

CONTACT

13902282893; zhangli6@mail.sysu.edu.cn

Wenfeng Fang, Doctor

CONTACT

15322302066; fangwf@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2022
• First Posted: March 17, 2022
• Study Start: March 11, 2022
• Primary Completion: April 1, 2024
• Study Completion: June 1, 2024
• Last Updated: March 17, 2022

Record last verified: 2022-03

Locations

CN (9)