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

Non Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02485652
• Other study ID #: HM-EMSI-202
• Secondary ID: 2015-001435-21
• Status: Terminated
• Phase: Phase 2
• Start date: August 31, 2015
• Est. completion date: December 8, 2020

Study information

• Verified date: January 2021
• Source: Hanmi Pharmaceutical Company Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 162
• Est. completion date: December 8, 2020
• Est. primary completion date: December 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Drug:
• HM61713
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 investigator"s opinion, they are benefiting from study treatment and they do not meet any of treatment discontinuation criteria.

Locations

Country	Name	City	State
Australia	Research Site	Darlinghurst
Australia	Research site	Fitzroy
Australia	Research Site	Frankston
Australia	Research Site	Kogarah
Australia	Research Site	St Albans
Australia	Research Site	Woolloongabba
Canada	Research Site	Toronto
Germany	Research Site	Berlin
Germany	Research Site	Homburg
Germany	Research Site	Leipzig
Germany	Research Site	München
Germany	Research Site	Ulm
Italy	Research Site	Bergamo
Italy	Research Site	Bologna
Italy	Research Site	Catania
Italy	Research Site	Milano
Italy	Research Site	Rome
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Hwasun
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site 2	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site 2	Seoul
Korea, Republic of	Research Site 3	Seoul
Korea, Republic of	Research Site 4	Seoul
Korea, Republic of	Research Site 5	Seoul
Korea, Republic of	Research Site 6	Seoul
Korea, Republic of	Research Site 7	Seoul
Korea, Republic of	Research Site 8	Seoul
Malaysia	Research Site	George Town	Penang
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuantan
Malaysia	Research Site	Kuching
Philippines	Research Site	Cebu
Philippines	Research Site	Makati	Kalakhang Maynila
Philippines	Research Site	Manila	Metro Manila
Philippines	Research Site 2	Manila	Metro Manila
Philippines	Research Site	Pasig	Manila
Spain	Research Site	Barcelona
Spain	Research Site 2	Barcelona
Spain	Research Site 3	Barcelona
Spain	Research Site 4	Barcelona
Spain	Research Site	La Coruna
Spain	Research Site	Madrid
Spain	Research Site 2	Madrid
Spain	Research Site	Navarra
Spain	Research Site	San Sebastian
Spain	Research Site	Valencia
Spain	Research Site 2	Valencia
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site 2	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site 2	Taipei
United States	Research Site	Bethesda	Maryland
United States	Research Site	Beverly Hills	California
United States	Research Site	Boca Raton	Florida
United States	Research Site	Boston	Massachusetts
United States	Research Site	Burbank	California
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Evanston	Illinois
United States	Research Site	Honolulu	Hawaii
United States	Research Site	Lebanon	New Hampshire
United States	Research Site	Los Angeles	California
United States	Research Site 2	Los Angeles	California
United States	Research Site	Montebello	California
United States	Research Site	Orange	California
United States	Research Site	San Diego	California
United States	Research Site	Washington	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Hanmi Pharmaceutical Company Limited

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Germany,  Italy,  Korea, Republic of,  Malaysia,  Philippines,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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