Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Oral Once-Daily Administration of HS-10296 55mg

Oral Once-Daily Administration of HS-10296 110mg

Oral Once-Daily Administration of HS-10296 220mg

Oral Once-Daily Administration of HS-10296 260mg

Oral Once-Daily Administration of HS-10296 110mg (RP2D)

HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.

HS-10296

This is a Phase 1/2, open-label, multicenter study of HS-10296 with dose escalation, dose expansion and extension cohorts in locally advanced or metastatic non-small-cell lung cancer (NSCLC) patients who have progressed following prior therapy with an epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor (TKI) agent. The study is designed to evaluate safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of once-daily and orally (PO) administered HS-10296. The overall study design is shown in the flow chart below, which consists of 3 phases: dose escalation, dose expansion and extension cohort.

A Study to Evaluate Safety, PK and Efficacy of HS-10296 in Patients With NSCLC

A Phase 1/2, Open-label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics and Efficacy of HS-10296 in Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer

DLT is defined as one of the following HS-10296 related adverse event (AE) ：(1) Hematological toxicity ≥ Grade 4 neutropenia lasting more than 5 days, febrile neutropenia of any duration (absolute neutrophil count \[ANC\]) \< 1.0 × 109/L and fever ≥ 38.5°C), Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with bleeding, any requirement for platelet transfusion, Grade 4 anemia (unexplained by underlying disease); (2)Non-hematological toxicity ≥ CTCAE Grade 3 including Infection (including febrile neutropenia), confirmed prolongation of QT interval corrected with Fridericia's (QTcF) (\> 500 ms absolute or \> 60 ms above Baseline) and cardiac toxicity greater than Grade 3；(3)Any other toxicity that is greater than that at Baseline (clinically significant and/or unacceptable, and judged to be a DLT by the SRC), meets a protocol-defined stopping criteria (i.e., confirmed corneal ulceration), or results in a disruption of dosing schedule of more than 7 days.

ORR is defined as the percentage of patients with a complete response (CR) or partial response (PR) that was confirmed at a subsequent scan at least 6 weeks later, as assessed according to RECIST (Response Evaluation Criteria In Solid Tumors Criteria) version 1.1 for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition can be symptoms (e.g., nausea, chest pain), signs (e.g., tachycardia, enlarged liver), or the abnormal results of an investigation (e.g., laboratory findings, ECG). Any deterioration of the disease under study and associated symptoms or findings should not be regarded as an AE as far as the deterioration can be anticipated. The AE was graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.

Area under the plasma concentration versus time curve from time zero to the 24-hour sampling time at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-24 was to be calculated according to the mixed log-linear trapezoidal rule.

Elimination half-life is the time measured for the concentration to decrease by one half. Half-life calculated by natural log 2 divided by λz.

Observed maximum plasma concentration (Css max) after multiple dose of HS-10296 and HAS-719

Area Under the Plasma Concentration Versus Time Curve at steady state (AUCss) of HS-10296 and HAS-719 after multiple dose of HS-10296

The PFS is defined as the time from date of first dosing until the date of objective disease progression as defined by Response Evaluation Criteria in Solid Tumors （RECIST） v1.1 or death (by any cause in the absence of progression) regardless of whether the patients withdraws from HS-10296 therapy or receives another anti-cancer therapy prior to progression. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Objective response is assessed by RECIST 1.1 thereby to evaluate disease control rate. The DCR is defined as the proportion of patients with a best overall response of CR, PR, or SD (stable disease).

Overall survival will be assessed based on the date of first dose and survival status at the time of analysis. Overall survival is defined as the time from date of first dose until the documentation of death from any cause.

Depth of Response (DepOR) Only in part II dose-extention phase. DepOR is defined as the percentage change in tumor size, based on longest diameter or reconstructed volume, observed at the lowest point compared with baseline.

Duration of response (DoR) is defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression. The end of response should coincide with the date of progression or death from any cause used for the PFS endpoint. The time of the initial response will be defined as the latest of the dates contributing towards the first visit response of PR or CR. If a patient does not progress following a response, then DoR will be used as the PFS censoring time.

Jiangsu Hansoh Pharmaceutical Co., Ltd.

Oral Once-Daily Administration of HS-10296 55mg

HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.

Escalation Cohort 1

Oral Once-Daily Administration of HS-10296 110mg

HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.

Escalation Cohort 2

Oral Once-Daily Administration of HS-10296 220mg

HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.

Escalation Cohort 3

Oral Once-Daily Administration of HS-10296 260mg

HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.

Escalation Cohort 4

Expansion Cohort 1

Expansion Cohort 2

Expansion Cohort 3

Oral Once-Daily Administration of HS-10296 (MTD or RP2D)

HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.

Phase 2 Extension

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

Taiwan

China

Region of Enrollment

Alison Li

Number of Participants With Dose Limiting Toxicity (DLT) Phase I Part

Overall Response Rate (ORR) Phase II Part

At least one adverse event

At least one adverse event of Grade 3 or greater

At least one serious adverse event

Incidence and Severity of Adverse Events (AEs) Phase I Part

HAS-719

Data was collected for only Part 1 dose escalation Arms

Area Under the Plasma Concentration Versus Time Curve (AUC) of HS-10296 and HAS-719 From Zero to the 24-Hour Sampling Time (AUC0-24) After Single Dose of HS-10296

Elimination Half-life(T1/2) of HS-10296 and HAS-719

Oral Once-Daily Administration of HS-10296 110mg (RP2D)

HS-10296: HS-10296: 5-, 10-, 40-, and 55-mg tablet, immediate-release formulation. Patients should avoid consumption of food for at least 1 hour prior to and 2 hours post dosing. RP2D is determined at 110 mg QD.

Css Max of HS-10296 and HAS-719 After Multiple Dose

AUCss of HS-10296 and HAS-719 After Multiple Dose of HS-10296

Overall Response Rate (Phase I Part)

Progression-free Survival (PFS)

Disease Control Rate (DCR)

Overall Survival (OS) Phase II Part

Based on the ICR evaluation results, DepOR analysis was performed on patients with efficacy evaluation

Spots Global Cancer Trial Database for A Study to Evaluate Safety, PK and Efficacy of HS-10296 in Patients With NSCLC

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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