A Phase I Study of NTQ1062 in Chinese Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is an open-label, single-arm, phase 1 study to evaluate the safety, tolerability, pharmacokinetics, and preliminary pharmacodynamic effect of NTQ1062 in patients with advanced solid tumors. The study comprises a dose-escalation phase and a dose-expansion phase. Dose-escalation:using 3+3 design to evaluate the safety, tolerability, and pharmacokinetic profile of NTQ1062 at 20, 50, 100, 200, 300, 400 mg in patients with advanced solid tumors, and to determine the maximum tolerated dose (MTD). Dose-expansion:the dose-expansion study will evaluate the safety, tolerability, and preliminary pharmacodynamic effect of the MTD for NTQ1062 in patients with advanced solid tumors, and to identify the recommended phase 2 dose (RP2D).

Official Title
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A Phase I Study of Safety, Tolerability, Pharmacokinetics and Preliminary Pharmacodynamic Effect of NTQ1062 Tablets in Chinese Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: NTQ1062


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged at least 18 years old, male or female patients. Patients with histologically and cytologically confirmed, advanced malignant solid tumors who have progressed on standard therapy or for whom no standard therapy exists, or for whom no standard treatment is available. (Dose escalation phase)Solid tumors that are at least one evaluable per Response Evaluation Criteria in Solid Tumors(RECIST v1.1);(Dose expansion phase)Solid tumors that are at least one measurable per Response Evaluation Criteria in Solid Tumors(RECIST v1.1). ECOG score is 0-1. Predicted life expectancy ≥3 months. Patients must have adequate organ function: Absolute neutrophil count (ANC) ≥ 1.5×109/L, platelet count ≥ 75×109/L, hemoglobin ≥ 85 g/L. Liver function: Total bilirubin ≤ 1.5xULN, AST and ALT ≤ 3.0xULN (≤ 5.0xULN for patients with Patients with hepatic metastases or hepatic carcinoma). Renal function:Creatinine (Cr) ≤ 1.5xULN or creatinine clearance (Ccr) ≥ 50 ml/min/1.73m2. Coagulation function: activated partial thromboplastin time (APTT) and INR ≤1.5×ULN. Female patients of child-bearing potential, and all male partners must consent to use a acceptable method of contraception throughout the study period and for 90 days after the last dose of either study drug. Patients must be signed written informed consent prior to admission to the study. Exclusion Criteria: Clinically significant abnormalities of glucose metabolism as defined by any of the following: Diagnosis of diabetes mellitus type I. Baseline fasting glucose value of ≥8.33 mmol/l (150 mg/dL). Glycosylated haemoglobin (HbA1C) ≥8%. Patients who are still receive anti-tumor therapy such as chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy and other anti-tumor drug from 4 weeks prior to the first dose. Patients have received previous treatment with a AKT,PI3K or mTOR inhibitor. Patients received strong inhibitors and/or inducers of CYP3A4 within 7 days prior to the first dose of study drug. Active infection requiring systemic treatment. Active hepatitis B virus infection or hepatitis C virus infection. History of human immunodeficiency virus infection. Patient has symptomatic CNS metastases. History of severe cardiovascular diseases. Other conditions that the investigator considers inappropriate for participation in this clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NTQ1062<br>NTQ1062 Tablets will be administered orally QD in a 28-day cycle (21 days on treatment followed by 7 days off treatment) in sequential cohorts. | Drug: NTQ1062<br>* tablet(s) PO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) | The MTD is defined as the highest dose reached for which the incidence of dose limiting toxicity (DLT) occurs in less than 1/3 of the subjects. | First treatment cycle (i.e., the first 28 days post the first dose) | 
| Recommended phase 2 dose (RP2D) | The RP2D of NTQ1062 will be determined during the dose-escalation phase of the study. RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data. | First treatment cycle (i.e., the first 28 days post the first dose) | 
| Adverse events | Safety and tolerability of NTQ1062. Incidence of adverse events. | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters:Cmax | Maximum Serum Concentration (Cmax) of NTQ1062. | At the end of Cycle 1 (each cycle is 28 days) | 
| Pharmacokinetic parameters: Tmax | Time to Maximum Serum Concentration (Tmax) of NTQ1062. | At the end of Cycle 1 (each cycle is 28 days) | 
| Pharmacokinetic parameters: AUC | The area under the concentration versus time curve of NTQ1062. | At the end of Cycle 1 (each cycle is 28 days) | 
| Pharmacokinetic parameters:T1/2 | The terminal half-life of NTQ1062. | At the end of Cycle 1 (each cycle is 28 days) | 
| Objective response rate (ORR) | ORR is defined as participants with confirmed complete or partial response (CR+PR) per RECIST, v1.1 | through study completion, an average of 1 year | 
| Disease Control Rate(DCR) | DCR was defined as the proportion of patients who had an overall response of complete response (CR), partial response (PR), or stable disease (SD). | through study completion, an average of 1 year | 
| Duration of Response(DOR) | DOR is defined as the time between date of first response and the first occurrence. of progression or death from any cause, whichever occurs first. | through study completion, an average of 1 year | 
| Progression-free Survival(PFS) | PFS will be defined as the time between the first dose of any study drug and the first occurrence of progression or death from any cause. | through study completion, an average of 1 year |