Phase II Trial of HM61713 for the Treatment of ≥2nd Line T790M Mutation Positive Adenocarcinoma of the Lung

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, safety and pharmacokinetics of HM61713 in patients with T790M-positive non-small cell lung cancer (NSCLC) after treatment with an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI).

Detailed Description
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This is a single-arm, open-label, Phase 2 study to assess the anti-tumor efficacy of oral single agent HM61713 administered to patients with T790M-positive NSCLC after treatment with an EGFR-TKI as measured by objective response rate (ORR).

Official Title
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A Single Arm, Open-label, Phase 2 Study Evaluating the Efficacy, Safety and PK of HM61713 in Patients With T790M-positive NSCLC After Treatment With an Epidermal Growth Factor Receptor-tyrosine Kinase Inhibitor

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: HM61713


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: at least 20 years of age Cytologically or histologically confirmed adenocarcinoma of locally advanced or metastatic NSCLC which is not amenable to curative surgery or radiotherapy Radiologically confirmed disease progression after at least one line of treatment with an EGFR-TKI At least one documented EGFR mutation which is known to be related with susceptibility to EGFR-TKIs (including G719X, exon 19 deletion, L858R, and L861Q) World Health Organization (WHO) performance score of 0 to 1 with life expectancy of at least 3 months Centrally confirmed T790M mutation positive tumor status from a tumor sample taken after confirmation of disease progression on the most recent anticancer treatment regimen At least one lesion (excluding the brain), not previously irradiated that can be accurately measured per RECIST version 1.1 Adequate hematological and biological function Females of child-bearing potential must agree to use adequate contraception and for 3 months after the last dose of study drug Male patients should be documented to be sterile or agree to use barrier contraception Recovery to ≤ Grade 1 or baseline of any toxicities, except for stable sensory neuropathy ≤ Grade 2 and alopecia Exclusion Criteria: Known history of hypersensitivity to active or inactive excipients of HM61713 or drugs with a similar chemical structure of HM61713 Previous treatment with anticancer therapies, EGFR-TKI, HM61713, or other drugs that target T790M-positive mutant EGFR with sparing of wild-type, investigational agent(s) within 28 days prior to the first administration of study drug, radiotherapy Any non-study related significant surgical procedures within the past 28 days prior to the first administration of study drug Spinal cord compression, leptomeningeal carcinomatosis or active symptomatic brain metastases History of any other malignancy Clinically significant uncontrolled condition(s) Active or chronic pancreatitis Anyone with cardiac abnormalities or history Presence or history of ILD, drug-induced ILD, or presence of radiation pneumonitis Pregnant or breast feeding In the opinion of the investigator, the patient is an unsuitable candidate to receive HM61713

Ages Eligible for Study
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Minimum Age: 20 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: HM61713<br>HM61713 800 mg (2 x 400 mg tablets) once daily (QD) | Drug: HM61713<br>* 800 mg QD continuously in 21-day cycles until disease progression determined by investigator assessment per RECIST version 1.1, and as long as, in the investigators opinion, they are benefiting from study treatment and they do not meet any of treatment discontinuation criteria.<br>* Other names: Olmutinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | To assess the anti-tumor efficacy of HM61713 as measured by objective response rate (ORR). | At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate (DCR), defined as the proportion of patients with a documented CR, PR, and SD during the treatment cycles according to the RECIST version 1.1 | To assess clinical efficacy of HM61713 regarding disease control rate (DCR). | At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months | 
| Duration of overall tumor response (DR), defined as the interval between the date of the first observation of tumor response (CR or PR) and the date of disease progression or death | To assess clinical efficacy of HM61713 regarding Duration of overall tumor response (DR). | At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months | 
| Progression-free survival (PFS), defined as the time from first administration of study drug to determination of tumor progression by RECIST version 1.1 or death due to any cause, whichever occurs first | To assess clinical efficacy of HM61713 regarding Progression-free survival (PFS). | At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months | 
| Overall survival (OS), defined as the time from first administration of study drug until death from any cause | To assess clinical efficacy of HM61713 regarding Overall survival (OS). | From first dose to end of study or date of death from any cause whichever came first, assessed up to 48 months | 
| Time to progression (TTP), defined as the time from first administration of study drug to determination of tumor progression by RECIST version 1.1 | To assess clinical efficacy of HM61713 regarding Time to progression (TTP). | At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months | 
| Tumor shrinkage calculated as absolute change and percentage change from baseline in sum of tumor size at each assessment using RECIST tumor response | To assess clinical efficacy of HM61713 regarding tumor shrinkage. | At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months | 
| Peak concentration (Cmax) of HM61713 | To determine the pharmacokinetic (PK) profile of HM61713. | Pre-dose (-30 to 0 mins) and 1 hour (± 5 mins), 3, 4, 6 hours (± 10 mins) on Day 1 and Day 15 of Cycle 1 and pre-dose (-30 to 0 mins) only on Day 8 of Cycle 1 and Day 1 of Cycle 2 (Day 22) | 
| Trough plasma concentration (Ctrough) of HM61713 | To determine the pharmacokinetic (PK) profile of HM61713. | Pre-dose (-30 to 0 mins) and 1 hour (± 5 mins), 3, 4, 6 hours (± 10 mins) on Day 1 and Day 15 of Cycle 1 and pre-dose (-30 to 0 mins) only on Day 8 of Cycle 1 and Day 1 of Cycle 2 (Day 22) | 
| Area under the plasma concentration time curve over the 24-hour dosing interval (AUC) of HM61713 | To determine the pharmacokinetic (PK) profile of HM61713. | Pre-dose (-30 to 0 mins) and 1 hour (± 5 mins), 3, 4, 6 hours (± 10 mins) on Day 1 and Day 15 of Cycle 1 and pre-dose (-30 to 0 mins) only on Day 8 of Cycle 1 and Day 1 of Cycle 2 (Day 22) | 
| Patient reported outcomes (PROs) | To assess patient reported outcomes (PROs) of health-related quality of life (HRQoL), disease/treatment-related symptoms of lung cancer, and general health status. | At baseline and every 6 weeks from time of discontinuation, assessed up to 24 months | 
| ECG/QTc (absolute values and change from baseline) | To evaluate the effect of HM61713 on the QT interval. | Adverse events will be collected from baseline until 28 days after the last dose | 
| Incidence of reported AEs and abnormal laboratory tests (AEs will be assessed using the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 4). | To assess the safety and tolerability of HM61713. | Adverse events will be collected from baseline until 28 days after the last dose | 
| QTc interval as assessed by digital ECG with central reading. The QT interval will be rate-corrected using 3 methods: QTcF, QTcB and QTcS. | To assess the safety and tolerability of HM61713. | Adverse events will be collected from baseline until 28 days after the last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, EGFR-TKI, non small cell lung cancer, HM61713, T790M-positive, lung cancer, Phase II, Olmutinib