Clinical trial NCT02485652: Phase II Trial of HM61713 for the Treatment of ≥2nd Line T790M Mutation Positive Adenocarcinoma of the Lung
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
Keywords: NSCLC
EGFR-TKI
non small cell lung cancer
HM61713
T790M-positive
lung cancer
Phase II
Olmutinib
Lead sponsor: Hanmi Pharmaceutical Company Limited
Sponsor class: INDUSTRY
First posted: 2015-06-30
Enrollment: 162
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months
Secondary outcomes:
measure: 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
timeFrame: At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months
measure: 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
timeFrame: At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months
measure: 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
timeFrame: At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months
measure: Overall survival (OS), defined as the time from first administration of study drug until death from any cause
timeFrame: From first dose to end of study or date of death from any cause whichever came first, assessed up to 48 months
measure: Time to progression (TTP), defined as the time from first administration of study drug to determination of tumor progression by RECIST version 1.1
timeFrame: At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months
measure: Tumor shrinkage calculated as absolute change and percentage change from baseline in sum of tumor size at each assessment using RECIST tumor response
timeFrame: At baseline and every 6 weeks from time of first dose until date of progression, assessed up to 12 months
measure: Peak concentration (Cmax) of HM61713
timeFrame: 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)
measure: Trough plasma concentration (Ctrough) of HM61713
timeFrame: 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)
measure: Area under the plasma concentration time curve over the 24-hour dosing interval (AUC) of HM61713
timeFrame: 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)
measure: Patient reported outcomes (PROs)
timeFrame: At baseline and every 6 weeks from time of discontinuation, assessed up to 24 months
measure: ECG/QTc (absolute values and change from baseline)
timeFrame: Adverse events will be collected from baseline until 28 days after the last dose
measure: 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).
timeFrame: Adverse events will be collected from baseline until 28 days after the last dose
measure: QTc interval as assessed by digital ECG with central reading. The QT interval will be rate-corrected using 3 methods: QTcF, QTcB and QTcS.
timeFrame: Adverse events will be collected from baseline until 28 days after the last dose
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Research Site
state: California
city: Burbank
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site 2
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Montebello
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Boca Raton
country: United States
facility: Research Site
state: Florida
city: Honolulu
country: United States
facility: Research Site
state: Hawaii
city: Evanston
country: United States
facility: Research Site
state: Illinois
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Lebanon
country: United States
facility: Research Site
state: New Hampshire
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Washington
country: United States
facility: Research Site
state: Washington
city: Darlinghurst
country: Australia
facility: Research Site
city: Fitzroy
country: Australia
facility: Research site
city: Frankston
country: Australia
facility: Research Site
city: Kogarah
country: Australia
facility: Research Site
city: St Albans
country: Australia
facility: Research Site
city: Woolloongabba
country: Australia
facility: Research Site
city: Toronto
country: Canada
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Homburg
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Ulm
country: Germany
facility: Research Site
city: Bergamo
country: Italy
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Catania
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Rome
country: Italy
facility: Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Hwasun
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site 2
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site 2
city: Seoul
country: Korea, Republic of
facility: Research Site 3
city: Seoul
country: Korea, Republic of
facility: Research Site 4
city: Seoul
country: Korea, Republic of
facility: Research Site 5
city: Seoul
country: Korea, Republic of
facility: Research Site 6
city: Seoul
country: Korea, Republic of
facility: Research Site 7
city: Seoul
country: Korea, Republic of
facility: Research Site 8
city: Seoul
country: Korea, Republic of
facility: Research Site
city: George Town
country: Malaysia
facility: Research Site
state: Penang
city: Kuala Lumpur
country: Malaysia
facility: Research Site
city: Kuantan
country: Malaysia
facility: Research Site
city: Kuching
country: Malaysia
facility: Research Site
city: Makati
country: Philippines
facility: Research Site
state: Kalakhang Maynila
city: Pasig
country: Philippines
facility: Research Site
state: Manila
city: Manila
country: Philippines
facility: Research Site 2
state: Metro Manila
city: Manila
country: Philippines
facility: Research Site
state: Metro Manila
city: Cebu
country: Philippines
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site 2
city: Barcelona
country: Spain
facility: Research Site 3
city: Barcelona
country: Spain
facility: Research Site 4
city: Barcelona
country: Spain
facility: Research Site
city: La Coruna
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site 2
city: Madrid
country: Spain
facility: Research Site
city: Navarra
country: Spain
facility: Research Site
city: San Sebastian
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site 2
city: Valencia
country: Spain
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site 2
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site 2
city: Taipei
country: Taiwan
facility: Research Site
Study officials:
affiliation: Sungkyunkwan University, Samsung Medical Center, Seoul, Republic of Korea
name: Keunchil Park, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Dana-Farber Cancer Institute, Boston, MA, USA
name: Pasi A. Jänne, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References: