A study to assess effects (how safe and effective) of HM61713 (BI 1482694) (new medicine) on specific type of non-small cell lung cancer, which characterized by being positive to certain type of mutation (T790M) , after treatment with a class of drugs known as (EGFR-TKI). The study will also test the drug concentrations’ changes in the patient blood at certain time points.

Phase 1

• Conditions: on-small cell lung cancer (NSCLC); MedDRA version: 19.0Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-001435-21-DE
• Lead Sponsor: Hanmi Pharmaceutical Co., Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-12-21
• Last Update Posted: 30 March 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

1. Provide written informed consent before any study-specific procedures (including special Screening tests) are performed.
2. At least 20 years of age at the time of signing informed consent.
3. Cytologically or histologically confirmed adenocarcinoma of locally advanced or metastatic NSCLC which is not amenable to curative surgery or radiotherapy.
4. Radiologically confirmed disease progression after at least one line of treatment with an EGFR-TKI with or without at least one line of chemotherapy.
5. 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).
6. World Health Organization (WHO) performance score of 0 to 1 with life expectancy of at least 3 months.
7. Centrally confirmed T790M mutation positive tumor status from a tumor sample taken after confirmation of disease progression on the most recent anticancer treatment regimen.
8. At least one lesion (excluding the brain), not previously irradiated that can be accurately measured per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
9. Adequate hematological and biological function as follows:
a. Absolute neutrophil count (ANC) = 1.5 x 109/L; hemoglobin = 9.0 g/dL; platelets = 100 x 109/L without the use of hematopoietic growth factors.
b. Total bilirubin = 1.5 times the upper limit of normal (ULN), or = 4 x ULN for patients who are known to have Gilbert’s syndrome.
c. Creatinine = 1.5 x ULN.
d. Aspartate transaminase (AST) and ALT = 3 x ULN if no demonstrable liver metastases, or otherwise = 5 x ULN.
e. Potassium and magnesium = 1.0 x ULN (supplementation is permissible).
10. Females of child-bearing potential (not surgically sterilized and between menarche and one-year post-menopause) must agree to use adequate contraception (one of the following listed below) during the study (both men and women as appropriate) and for 3 months after the last dose of study drug. Subjects who are not surgically sterilized must have a negative urine or serum pregnancy test completed during the Screening period. The following measures need to be followed for females of child-bearing potential:
a. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal).
b. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable).
c. Intrauterine device (IUD).
d. Intrauterine hormone-releasing system (IUS).
e. Bilateral tubal occlusion.
f. Vasectomised partner.
g. Sexual abstinence.
11. Male patients should be documented to be sterile or agree to use barrier contraception i.e. condoms.
12. Recovery to = Grade 1 or baseline of any toxicities due to prior treatments, except for stable sensory neuropathy
= Grade 2 and alopecia.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

1. Known history of hypersensitivity to active or inactive excipients of HM61713 or drugs with a similar chemical structure of HM61713.
2. Treatment with any of the following:
a. Anticancer therapies including chemotherapy, hormonal treatment, or immunotherapy within 14 days of the first administration of study drug.
b. Treatment with an EGFR-TKI (including erlotinib, gefitinib, and afatinib) within 8 days or 5-fold half-life, whichever is the longer, of the first administration of study drug.
c. Previous treatment with the combination of afatinib+cetuximab HM61713, or other drugs that target T790M-positive mutant EGFR with sparing of wild-type EGFR (e.g. AZD9291, CO-1686).
d. Treatment with any investigational agent(s) within 28 days prior to the first administration of study drug.
e. Radiotherapy with wide-field or more than 30% of the bone marrow within the past 2 weeks prior to the first administration of study drug; localized palliative radiation (e.g. localized skeletal metastasis) is permitted.
f. Any non-study related significant surgical procedures within the past 28 days prior to the first administration of study drug, except those related to this study.
3. Spinal cord compression, leptomeningeal carcinomatosis or active symptomatic brain metastases except for the followings:
a. Asymptomatic brain metastases incidentally found during screening process which do not require corticosteroids and/or local treatment in the opinion of the investigator.
b. Asymptomatic brain metastases for which local treatment has been given; at least 1 week off corticosteroids and/or anticonvulsants treatment before study randomization.
4. History of any other malignancy (other than curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors Ta [non-invasive tumor] and TIS [carcinoma in situ]) unless it has been definitively treated with no ongoing therapy or evidence of relapse or recurrence within the past 3 years.
5. Clinically significant uncontrolled condition(s), including but not limited to:
a. Refractory nausea and vomiting, inability to swallow the formulated product, or any gastrointestinal disorder, which may interfere with the administration or metabolism of the study drug.
b. Active infection that requires parenteral antibiotics.
c. Known human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C.
d. Psychiatric illness/social situations that would limit compliance with study requirements.
e. Known or suspected substance abuse or alcohol abuse.
f. Any medical condition which, in the opinion of the investigator, places the patient at an unacceptably high risk for toxicities.
6. Active or chronic pancreatitis assessed by the investigator
7. Any of the following cardiac abnormalities or history:
a. Abnormal 12-lead ECG considered to be clinically significant by the investigator.
b. Mean QT interval corrected using Fridericia’s (QTcF) method > 450 msec.
c. Personal or family history of long QT syndrome, second or third degree heart block.
d. Implanted pacemaker or cardioverter defibrillator.
e. Resting bradycardia < 55 beats/min.
f. Uncontrolled hypertension.
g. New York Heart Association (NYHA) class III or IV cardiac insufficiency, experienced unstable angina pectoris or cardiac infarction within 6 months, uncontrolled cardiac arrhythmia.
h. Left ventricular ejection fraction (LVEF) < 40%.
8. Presence or history of interstitial lung disease (ILD), drug-induced ILD, or presence of r

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified