D-0316 in Patients With EGFR Positive Non Small Cell Lung Cancer

Study Overview
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Brief Summary
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A Phase II, Open Label, Single-arm Study to Assess the Safety and Efficacy of D-0316 in Patients with Locally Advanced/Metastatic Non Small Cell Lung Cancer whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours are Epidermal Growth Factor Receptor Mutation and T790M Mutation Positive

Detailed Description
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This is a phase II, open label, single arm study assessing the safety and efficacy of D-0316 (Firstly, D-0316 was orally given 75mg for a cycle(21 days), if tolerated, the dose will be increased to 100mg. Otherwise, the dose will be maintained at 75mg.) in patients with a confirmed diagnosis of Epidermal Growth Factor Receptor mutation positive and T790M mutation positive NSCLC,who have progressed following prior therapy with an approved Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) agent. The primary objective of the study is to assess the efficacy of D-0316 by assessment of Objective Response Rate according to RECIST 1.1 by an Independent Central Review.

Official Title
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A Phase II Study to Assess the Safety and Efficacy of D-0316 in Patients With Locally Advanced/Metastatic Non Small Cell Lung Cancer Whose Tumors Are Epidermal Growth Factor Receptor Mutation Positive

Conditions
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Solid Tumor, NSCLC, EGFR T790M

Intervention / Treatment
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* Drug: D-0316


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged at least 18 years. Histologically or cytologically proven diagnosis of NSCLC that is locally advanced or metastatic. Radiological documentation of disease progression while on a previous continuous treatment with an first or second generation of EGFR TKI e.g. gefitinib or erlotinib. patients must also have confirmation of tumour T790M mutation status (confirmed positive) after disease progression on the prior EGFR TKI. Eastern cooperative oncology group performance status (ECOG PS) of 0-1. a minimum life expectancy of 12 weeks. At least one lesion, not previously irradiated during the study screening period, that can be accurately measured at baseline according to RECIST 1.1. Agree to use routine adequate and effective contraceptive measures during the entire study period and within 6 weeks after the last dose pre-menopausal fertility possible; Female patients need to exclude pregnancy (ie negative pregnancy test) and in non-lactation period. Exclusion Criteria: Treatment with a first or second generation of EGFR-TKI within 10 days of study entry; previous treatment with a third generation of EGFR-TKI. Unresolved toxicities from prior therapy. Unstable spinal cord compression/brain metastases. Severe/uncontrolled systemic diseases, including uncontrolled hypertension, bleeding diatheses or infection. QTcF≥470 msec（female）or QTcF≥450 msec（male）during the screening period. Severe respiratory diseases such as interstitial lung disease, severe asthma, pulmonary embolism, etc. previous treatment with 2 or more lines of Chemotherapy or immunotherapy.

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: D-0316<br>Firstly, D-0316 was orally given 75mg for a cycle(21 days), if tolerated, the dose will be increased to 100mg. Otherwise, the dose will be maintained at 75mg. | Drug: D-0316<br>* Firstly, D-0316 was orally given 75mg for a cycle(21 days), if tolerated, the dose will be increased to 100mg. Otherwise, the dose will be maintained at 75mg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate based on independent radiology review | ORR per RECIST 1.1 calculated as the proportion of patients with a best overall response defined as complete response (CR) or partial response (PR). | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) as assessed by independent radiology review and investigator | PFS, defined as time from first dose of X-396 to progression or death due to any cause. | 36 months | 
| Overall survival (OS) | OS, defined as time from first dose of X-396 to death due to any cause. | 36 months | 
| Duration of response(DoR) | DoR, defined as time from first reponse to disease progression or death | 24 months | 
| Disease control rate(DCR) | DCR, defined as proportion of complete response, partial response, and disease stabilization to the proportion of patients with evaluable tumors. | 24 months | 
| Intracranial Progression-free survival(iPFS) | iPFS, defined as the time between baseline brain metastases, from the date of study drug administration to the time between the onset of intracranial tumor progression or death. | 36 months | 
| Intracranial objective response rate(iORR) | iORR, defined as the proportion of subjects with complete intracranial response, partial intracranial response to subjects with brain metastases at baseline. | 24 months |