The purpose of this study is to evaluate the efficacy of Olmutinib(Olita®) in patients with
T790M-positive non-small cell lung cancer (NSCLC) confirmed using DNA extracted from
extracellular vesicles of bronchoalveolar lavage fluid.
This is a single-arm, open-label, Phase 2 study to assess the anti-tumor efficacy of
Olmutinib(Olita®) administered to patients with T790M-positive NSCLC confirmed using DNA
extracted from extracellular vesicles in bronchoalveolar lavage fluid as measured by
objective response rate (ORR).
Inclusion Criteria:
1. Male or female, aged at least 19 years
2. Obtained written informed consent
3. Histologically- or cytologically confirmed diagnosis of unresectable Stage IIIB or IV
non-small cell lung cancer.
4. Confirmation that the tumor harbours an EGFR mutation known to be associated with EGFR
TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q).
5. Eastern Cooperative Oncology Group performance status of 0 to 2
6. Prior treatment with at least one line of a single agent EGFR TKI (gefitinib,
erlotinib, afatinib) and confirmed progressive disease after treatment with EGFR TKI
- Regardless of treatment sequence between previous chemotherapy and EGFR TKI
- Regardless of whether they were administered conventional chemotherapy, if
therapy were treated with at least one EGFR TKI
7. Subjects who will undergo bronchoscopy/ BAL procedures and sufficient amount of BAL
fluid is carefully collected for EGFR mutation analysis.
8. Confirmation that the extracellular vesicles (EV) extracted from bronchoalveolar
lavage fluid (BALF) harbour T790M mutation (It can be replaced previous the same
result throughout the follow up period before enrollment.)
9. At least one measurable disease (except brain) at baseline according to RECIST version
1.1
10. Female subjects must be postmenopausal (for at least one year), or, if sexually
active, be practicing an effective method of birth control (e.g., prescription oral
contraceptives, contraceptive injections, intrauterine device, double-barrier method,
contraceptive patch, male partner sterilization) before entry and throughout the
study; and, for those of childbearing potential, have a negative urinary β-hCG
pregnancy test at screening.
11. Male subjects should be willing to use barrier methods which are suitable for sexual
partner throughout the study.
12. Subjects must have signed an informed consent document indicating that they understand
the purpose of and procedures required for the study and are willing to participate in
the study. The subject also must sign and date the consent form before specific
procedures or sampling.
13. Adequate organ function as defined by liver, kidney, and hematologic laboratory
testing as below
- Absolute neutrophil count (ANC) ≥ 1500/mm3, Platelet ≥ 100,000 /mm3 Hemoglobin
(Hb) ≥ 9.0g/dL
- Serum creatinine ≤ upper limit of normal (ULN)
- AST/ALT/ALP ≤ 3 times ULN, Total bilirubin ≤2.0 mg/dL AST/ALT/ALP ≤ 5 times ULN
in patients with metastatic lesions to the liver ALP ≤ 5 times ULN in patients
with metastatic lesions to the bone
14. Expected survival of at least 12 weeks
Exclusion Criteria:
1. Previous treatment with anticancer therapies, EGFR-TKI, olmutinib (HM61713), or other
drugs that target T790M-positive mutant EGFR with sparing of wild-type, Osimertinib
(AZD9291), Rociletinib (CO-1686), investigational agent(s) within 30 days prior to the
first administration of study drug, radiotherapy
2. Treatment with a potent cytochrome P450 (CYP) 3A4 inhibitors or inducers
3. History of any other malignancy EXCEPTIONS are:
- adequately treated non-melanoma skin cancer, curatively treated in situ cancer of
the cervix, ductal carcinoma in situ (DCIS) of the breast, thyroid cancer
- other malignancies diagnosed prior to randomisation and treated with no evidence
of disease recurrence more than 3 years
4. Any history or presence of clinically relevant cardiovascular abnormalities such as
uncontrolled hypertension, congestive heart failure NYHA classification of III or IV,
unstable angina or poorly controlled arrhythmia as determined by the investigator.
Myocardial infarction within 6 months prior to enrolment. Increased QTc interval > 450
ms on screening ECG
5. Any history of presence of interstitial lung disease
6. Any history or presence of poorly controlled gastrointestinal disorders that could
affect the absorption of the trial drug (e.g. Crohn's disease, ulcerative colitis,
chronic diarrhea, malabsorption).
7. Ongoing active infection with, hepatitis B virus (infection defined as a positive
HbsAg and/ or HBV DNA), hepatitis C virus (infection defined as a positive HCV RNA),
or human immunodeficiency virus (HIV) Type 1/2 infection at the time of screening.
8. Known history of hypersensitivity to active or inactive excipients of study drug
(olmutinib) or drugs with a similar chemical structure of olmutinib
9. Subjects with galactose intolerance, Lapp lactase deficiency or glucose-galactose
malabsorption
10. Symptomatic or uncontrolled central nervous system (CNS) metastases (Patients are
eligible if they have completed their treatment and have recovered from the acute
effects of radiation therapy or surgery prior to the start of study medication, have
discontinued corticosteroid treatment for these metastases for at least 4 weeks and
are neurologically and radiologically stable)
11. Uncontrolled active infectious disease (with the exception of those that are
considered to be needed topical antibiotics, however subjects can be enrolled into the
study after they complete their treatment)
12. Unable to attend all the study visits or comply with study procedures
13. Patients who had received other investigational product within 30 days prior to the
first administration of study drug except for gefitinib, erlotinib, or afatinib
