Non Small Cell Lung Cancer
Conditions
Keywords
NSCLC, EGFR-TKI, non small cell lung cancer, HM61713, T790M-positive, lung cancer, Phase II, Olmutinib
Brief summary
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
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).
Interventions
DRUGHM61713
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.
Sponsors
Hanmi Pharmaceutical Company Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months | To assess the anti-tumor efficacy of HM61713 as measured by objective response rate (ORR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months | To assess clinical efficacy of HM61713 regarding Duration of overall tumor response (DR). |
| 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 | At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months | To assess clinical efficacy of HM61713 regarding Progression-free survival (PFS). |
| Overall survival (OS), defined as the time from first administration of study drug until death from any cause | From first dose to end of study or date of death from any cause whichever came first, assessed up to 48 months | To assess clinical efficacy of HM61713 regarding Overall survival (OS). |
| Time to progression (TTP), defined as the time from first administration of study drug to determination of tumor progression by RECIST version 1.1 | At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months | To assess clinical efficacy of HM61713 regarding Time to progression (TTP). |
| Tumor shrinkage calculated as absolute change and percentage change from baseline in sum of tumor size at each assessment using RECIST tumor response | At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months | To assess clinical efficacy of HM61713 regarding tumor shrinkage. |
| Peak concentration (Cmax) 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) | To determine the pharmacokinetic (PK) profile of HM61713. |
| 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 | At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months | To assess clinical efficacy of HM61713 regarding disease control rate (DCR). |
| Area under the plasma concentration time curve over the 24-hour dosing interval (AUC) 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) | To determine the pharmacokinetic (PK) profile of HM61713. |
| Patient reported outcomes (PROs) | At baseline and every 6 weeks from time of discontinuation, assessed up to 24 months | To assess patient reported outcomes (PROs) of health-related quality of life (HRQoL), disease/treatment-related symptoms of lung cancer, and general health status. |
| ECG/QTc (absolute values and change from baseline) | Adverse events will be collected from baseline until 28 days after the last dose | To evaluate the effect of HM61713 on the QT interval. |
| 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). | Adverse events will be collected from baseline until 28 days after the last dose | To assess the safety and tolerability of HM61713. |
| QTc interval as assessed by digital ECG with central reading. The QT interval will be rate-corrected using 3 methods: QTcF, QTcB and QTcS. | Adverse events will be collected from baseline until 28 days after the last dose | To assess the safety and tolerability of HM61713. |
| Trough plasma concentration (Ctrough) 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) | To determine the pharmacokinetic (PK) profile of HM61713. |
Countries
Australia, Canada, Germany, Italy, Malaysia, Philippines, South Korea, Spain, Taiwan, United States
Outcome results
None listed