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Clinical Trials List

Protocol NumberG1T38-03
NCT Number(ClinicalTrials.gov Identfier)NCT03455829

2018-03-01 - 2019-09-30

Others

Terminated9

ICD-10C34

Malignant neoplasm of bronchus and lung

ICD-9162.9

Malignant neoplasm of bronchus and lung, unspecified

Phase 1b/2 Safety, Pharmacokinetic, and Efficacy Study of G1T38 in Combination with Osimertinib in Patients with EGFR Mutation-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC)

  • Trial Applicant

    PAREXEL INTERNATIONAL CO., LTD.

  • Sponsor

    G1 Therapeutics.

  • Trial scale

    Multi-Regional Multi-Center

  • Update

    2025/08/20

Investigators and Locations

Principal Investigator Wu-Chou Su Division of General Internal Medicine
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Stop recruiting

Audit

None

Principal Investigator 何景良 Division of Hematology & Oncology
Tri-Service General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Stop recruiting

Principal Investigator Gee-chen Chang Division of Thoracic Medicine
Taichung Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Stop recruiting

Principal Investigator 林孟志 Division of Thoracic Medicine
Kaoshiung Chang Gung Memorial Hospital of the C.G.M.F.

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Stop recruiting

Principal Investigator 魏裕峰 Division of Thoracic Medicine
E-DA Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Stop recruiting

Principal Investigator Chao-Hua Chiu Division of Hematology & Oncology
Taipei Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Stop recruiting

Principal Investigator Cheng-Ta Yang Division of Hematology & Oncology
Linkou Chang Gung Medical Foundation

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Stop recruiting

Audit

None

Principal Investigator Inn-Wen Chong 未分科
Kaohsiung Municipal Gangshan Hospital

Co-Principal Investigator

Audit

None

Principal Investigator James Chih-Hsin Yang Division of Hematology & Oncology
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Stop recruiting

Audit

None

Principal Investigator Inn-Wen Chong Division of Thoracic Medicine
Kaohsiung Medical Univeristy Chung-Ho Memorial Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Stop recruiting

Condition/Disease

Non-Small Cell Lung Cancer, NSCLC

Objectives

Primary Objectives -Evaluate DLTs associated with G1T38 administered with osimertinib -Determine the recommended Phase 2 dose of G1T38 administered withosimertinib -Evaluate the safety and tolerability of G1T38 administered with osimertinib -Assess PFS using BICR(RECIST v1.1) Secondary Objectives -Assess the effect of osimertinib on PK parameters of G1T38 -Assess PFS using investigator assessments (RECIST v1.1) -Assess response rate and CBR based on RECIST v1.1 (BICR and investigator assessed) -Assess OS -Assess 1-year PFS (BICR and investigator assessed)

Test Drug

G1T38

Active Ingredient

G1T38

Dosage Form

tablet
capsule

Dosage

50, 200, 250
25 or 100

Endpoints

Primary Outcome Measures :
Dose Limiting Toxicity [ Time Frame: Cycle 1 Day -14 to Cycle 1 Day 28 ]
Recommended Phase 2 dose [ Time Frame: 9 months ]
Number of Treatment Related Adverse Event, including Abnormal Laboratory Events [ Time Frame: 36 months ]
All AEs, including clinical laboratory, vitals signs, physical examinations and ECGs will be analyzed in all patients receiving study drug from the signing of the informed consent until 30 days after the last dose of study medication

Progression free survival (PFS) using blinded independent central review (BICR) [ Time Frame: 36 months ]

Secondary Outcome Measures :
Tumor response based on RECIST, Version 1.1 [ Time Frame: 21 months ]
Pharmacokinetics of G1T38 and metabolite G1T30: Maximum Plasma Concentration (Cmax) [ Time Frame: Part 1, Cycle 1 Day -14 to Day -2. Part 2, Cycle 1 Day 15 to Cycle 2 Day 1. ]
Pharmacokinetics of G1T38 and metabolite G1T30: Area under Curve - plasma concentration (AUC) [ Time Frame: Part 1, Cycle 1 Day -14 to Day -2. Part 2, Cycle 1 Day 15 to Cycle 2 Day 1. ]
Pharmacokinetics of G1T38 and metabolite G1T30: Plasma: terminal half life (T1/2) [ Time Frame: Part 1, Cycle 1 Day -14 to Day -2. Part 2, Cycle 1 Day 15 to Cycle 2 Day 1. ]
Pharmacokinetics of G1T38 and metabolite G1T30: Plasma - Volume of distribution [ Time Frame: Part 1, Cycle 1 Day -14 to Day -2. Part 2, Cycle 1 Day 15 to Cycle 2 Day 1. ]
PFS using investigator assessment [ Time Frame: 36 months ]
1-year PFS using investigator assessment and BICR [ Time Frame: 33 months ]
Overall survival (OS) [ Time Frame: 60 months ]

Inclution Criteria

Inclusion Criteria
Patient eligibility shall be reviewed and documented by an appropriately qualified member of
the investigator’s study team before patients are included in the study. Patients must meet all
of the following inclusion criteria to be eligible for enrollment into the study:
1. Provision of signed and dated written informed consent prior to any study specific
procedures, sampling, and analysis
2. Women or men, 18 years or older
3. Histologic or cytologic confirmed diagnosis of NSCLC
4. Stage IV NSCLC
5. Documented EGFR mutation (at any time since the initial diagnosis of NSCLC) known
to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R,
L861Q). Patients in Part 1 that are EGFR TKI treatment naive will be enrolled based on a
locally available EGFR mutation test result that has been FDA-approved and performed
in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory (US
sites) or based on a locally available EGFR mutation test result that has been performed
in an accredited laboratory (sites outside of the US).
a. Part 2 Only: Tumor EGFR T790M mutation-positive status after documented
disease progression on first-line treatment with a first or second generation
EGFR TKI. Patients will be enrolled based on a locally available T790M
mutation test result (tumor biopsy or cell-free DNA [cfDNA]) that has been
FDA-approved (eg, cobas® EGFR Mutation Test v2, FoundationOne CDx™)
and performed in a CLIA-certified laboratory (US sites) or a locally available
T790M mutation test result (tumor biopsy or cfDNA) that has been performed
in an accredited laboratory (sites outside of the US). Testing for the presence
of the T790M mutation in plasma specimens (cfDNA) is recommended only
in patients for whom a tumor biopsy cannot be obtained.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with no
deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks
7. Evaluable disease (Part 1 only) or measurable disease as defined in Response Evaluation
Criteria in Solid Tumors (RECIST), Version 1.1, as determined by the investigator
• Measurable disease is defined as having at least 1 lesion, not previously
irradiated, that can be accurately measured at baseline as ≥ 10 mm in the
longest diameter (except lymph nodes, which must have short axis ≥ 15 mm)
with computerized tomography (CT) or magnetic resonance imaging (MRI),
which is suitable for accurate repeated measurements.
8. Left ventricular ejection fraction (LVEF) ≥ institution’s lower limit of the reference range
9. Adequate bone marrow reserve or organ function as demonstrated by the following
laboratory values:
a. Hemoglobin ≥ 90 g/L
b. ANC ≥ 1.5 × 109
/L
c. Platelet count ≥ 100 × 109
/L
d. Calculated creatinine clearance ≥ 50 mL/min (by Cockcroft-Gault formula
[Cockcroft and Gault 1976] or 51Cr-EDTA)
e. Total bilirubin ≤ 1.5 × ULN; < 3 × ULN if the patient has documented
Gilbert’s disease or liver metastases
f. ALT < 2.5 × ULN if no demonstrable liver metastases or < 5 × ULN in the
presence of liver metastases
g. AST < 2.5 × ULN if no demonstrable liver metastases or < 5 × ULN in the
presence of liver metastases
10. Contraception: Patients must be willing to comply with the requirements for
contraception as described in Section 8.10

Additional criteria that apply to Part 2 only:
11. Measurable disease as defined in RECIST, Version 1.1, as determined by the investigator

Exclusion Criteria

Exclusion Criteria
A patient will not be eligible for participation in this study if any of the following criteria apply.
1. Treatment with any of the following:
a. EGFR TKI (eg, erlotinib, gefitinib, afatinib) within 9 days of the first dose of study drug
b. Investigational agents within 3 months, or 5 half-lives, whichever is longer, of the first dose of study drug
c. Part 1: More than 2 prior lines of cytotoxic chemotherapy for advanced NSCLC
d. Part 2: Previous treatment with osimertinib or other T790M active EGFR TKI
e. Part 2:Any prior cytotoxic chemotherapy for advanced NSCLC
2. Major surgery within 14 days of the first screening visit
3. Blood transfusions or hematopoietic growth factor therapy within 14 days prior of first screening visit
4. Prior radiotherapy treatment to > 25% of the bone marrow or radiotherapy with a wide
field of radiation within 28 days of the first dose of study drug
5. Patients receiving medications, herbal supplements, or foods known to be potent
inhibitors of CYP3A4 or orally administered sensitive substrates of CYP3A4 within 14
days prior to first dose of study drug, including but not limited to the following:
a. Inhibitors, for example: clarithromycin, diltiazem, erythromycin, grapefruit
juice, itraconazole, ketoconazole, nefazodone, ritonavir, telithromycin, and verapamil
b. Substrates, for example: astemizole, cisapride, cyclosporine,
dihydroergotamine, ergotamine, everolimus, pimozide, quinidine, sirolimus, and tacrolimus
6. Patients receiving medications, herbal supplements, or foods known to be potent inducers
of CYP3A4 within 21 days prior to the first dose of study drug, including but not limited to the following:
a. Inducers, for example: carbamazepine, Hypericum perforatum (St. John’s wort), phenobarbital, phenytoin, rifampin
7. Patients receiving medications, herbal supplements, or foods known to be potent
inhibitors of BCRP within 14 days prior to first dose of study drug, including but not limited to the following:
a. Inhibitors, for example: sulfasalazine, curcumin, turmeric supplements, cyclosporine, eltrombopag
8. Part 1: Patients receiving medications that raise gastric pH within 7 days prior to first
dose of study drug such as proton pump inhibitors (eg, omeprazole, pantoprazole,
lansoprazole, esomeprazole, rabeprazole, dexlansoprazole), H2 blockers (eg, nizatidine,
famotidine, cimetidine, ranitidine), and antacids (eg, sodium bicarbonate, calcium
carbonate, aluminum-based antacids, magnesium compounds, alginic acid).
9. Any unresolved toxicities from prior surgeries or therapy of > Grade 1 (CTCAE,
Version 4.03) at the time of starting study drug with the exception of alopecia (any grade)
and platinum therapy-related peripheral neuropathy (> Grade 2)
10. Known active uncontrolled or symptomatic central nervous system (CNS) metastases,
carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms,
cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or
cord compression are eligible if they are currently asymptomatic and clinically stable off
anticonvulsants and steroids for at least 28 days prior to first dose of G1T38.
11. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled
hypertension and active bleeding diatheses, which in the investigator’s opinion makes it
undesirable for the patient to participate in the study or which would jeopardize
compliance with the protocol
12. Known chronic, active infection including but not limited to hepatitis B virus, hepatitis C
virus, tuberculosis, and human immunodeficiency virus (HIV); screening for chronic conditions is not required
13. Any of the following cardiac criteria:
a. Mean resting corrected QT interval (QTc) > 470 msec obtained from
3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value
b. Any clinically important abnormalities in rhythm, conduction, or morphology
or resting ECG, eg, complete left bundle branch block, third degree heart
block, second degree heart block, PR interval > 250 msec
c. Any factors that increase the risk of QTc prolongation (see Appendix 3 for list
of drugs) or risk of arrhythmic events such as heart failure, hypokalemia,
congenital long QT syndrome, family history of long QT syndrome or
unexplained sudden death under 40 years of age in first degree relatives, or
any concomitant medication known to prolong the QT interval
d. Uncontrolled ischemic heart disease or uncontrolled symptomatic congestive
heart failure (Class III or IV as defined by the New York Heart Association
[NYHA] functional classification system)
e. Known history of stroke, cerebrovascular accident, or myocardial infarction
within 6 months prior to first dose of study drug
14. Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation
pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
15. Refractory nausea and vomiting, chronic gastrointestinal disease, gastrointestinal ulcer,
gastrointestinal bleeding, inability to swallow the formulated product, or previous
significant bowel resection that would preclude adequate absorption of study drug 16. History of other malignancies, except for the following: (1) adequately treated basal or
squamous cell carcinoma of the skin; (2) curatively treated a) in situ carcinoma of the
uterine cervix, b) prostate cancer, or c) superficial bladder cancer; or (3) other curatively
treated solid tumor with no evidence of disease for ≥ 3 years
17. History of hypersensitivity to active or inactive excipients of study drug or drugs with a
similar chemical structure or class to study drug
18. Women who are pregnant or breastfeeding
19. Psychiatric illness/social situations that would limit study compliance
20. Legal incapacity or limited legal capacity
21. Judgement by the investigator that the patient should not participate in the study if the
patient is unlikely to comply with study procedures, restrictions, and requirements
22. Prior hematopoietic stem cell or bone marrow transplantation

The Estimated Number of Participants

  • Taiwan

    86 participants

  • Global

    316 participants

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