This is a study to investigate the potential clinical benefit of G1T38 as an oral therapy in combination with osimertinib in patients with EGFR mutation-positive metastatic non-small cell lung cancer. The study is an open-label design, consists of 2 parts: safety, pharmacokinetic, and dose-finding portion (Part 1), and randomized portion (Part 2). Both parts include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of first dose with study treatment and completes at the Post-Treatment Visit. Approximately, 144 patients will be enrolled in the study.
Name: G1T38
Description: CDK 4/6 inhibitorType: DrugPart 1: G1T38 + Osimertinib Part 2: G1T38 + Osimertinib
Name: Osimertinib
Description: EGFR TKI; 80 mgType: DrugPart 1: G1T38 + Osimertinib Part 2: G1T38 + Osimertinib Part 2: Osimertinib
Description: 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
Measure: Number of Treatment Related Adverse Event, including Abnormal Laboratory Events Time: 36 monthsAllocation: Randomized
Parallel Assignment
There is one SNP
Inclusion Criteria: - Confirmed EGFR mutation for non-small cell lung cancer associated with EGFR TKI sensitivity - For Part 2, EGFR T790M mutation-positive tumor status - Left ventricular ejection fraction (LVEF) ≥ institution's lower limit of the reference range - For Part 1, evaluable or measurable disease as defined by RECIST, Version 1.1 - For Part 2, measurable disease as defined by RECIST, Version 1.1 - ECOG performance status 0 to 1 - Adequate organ function Exclusion Criteria: - Prior treatment with EGFR TKI within 9 days of first study dose - For Part 1, prior treatment with more than 2 prior lines of chemotherapy for advanced NSCLC - For Part 2, prior treatment with osimertinib or other T790M active EGFR TKI - For Part 2, prior chemotherapy for advanced NSCLC - Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease - Investigational drug within 3 months or 5 half-lives, whichever is longer, of first study dose - Concurrent radiotherapy, radiotherapy within 28 days of first study dose, previous radiotherapy to the target lesion sites, or prior radiotherapy to > 25% of bone marrow - Prior hematopoietic stem cell or bone marrow transplantation Inclusion Criteria: - Confirmed EGFR mutation for non-small cell lung cancer associated with EGFR TKI sensitivity - For Part 2, EGFR T790M mutation-positive tumor status - Left ventricular ejection fraction (LVEF) ≥ institution's lower limit of the reference range - For Part 1, evaluable or measurable disease as defined by RECIST, Version 1.1 - For Part 2, measurable disease as defined by RECIST, Version 1.1 - ECOG performance status 0 to 1 - Adequate organ function Exclusion Criteria: - Prior treatment with EGFR TKI within 9 days of first study dose - For Part 1, prior treatment with more than 2 prior lines of chemotherapy for advanced NSCLC - For Part 2, prior treatment with osimertinib or other T790M active EGFR TKI - For Part 2, prior chemotherapy for advanced NSCLC - Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease - Investigational drug within 3 months or 5 half-lives, whichever is longer, of first study dose - Concurrent radiotherapy, radiotherapy within 28 days of first study dose, previous radiotherapy to the target lesion sites, or prior radiotherapy to > 25% of bone marrow - Prior hematopoietic stem cell or bone marrow transplantation Carcinoma, Non-Small-Cell Lung Lung Cancer Non-small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung null --- T790M ---
Inclusion Criteria: - Confirmed EGFR mutation for non-small cell lung cancer associated with EGFR TKI sensitivity - For Part 2, EGFR T790M mutation-positive tumor status - Left ventricular ejection fraction (LVEF) ≥ institution's lower limit of the reference range - For Part 1, evaluable or measurable disease as defined by RECIST, Version 1.1 - For Part 2, measurable disease as defined by RECIST, Version 1.1 - ECOG performance status 0 to 1 - Adequate organ function Exclusion Criteria: - Prior treatment with EGFR TKI within 9 days of first study dose - For Part 1, prior treatment with more than 2 prior lines of chemotherapy for advanced NSCLC - For Part 2, prior treatment with osimertinib or other T790M active EGFR TKI - For Part 2, prior chemotherapy for advanced NSCLC - Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease - Investigational drug within 3 months or 5 half-lives, whichever is longer, of first study dose - Concurrent radiotherapy, radiotherapy within 28 days of first study dose, previous radiotherapy to the target lesion sites, or prior radiotherapy to > 25% of bone marrow - Prior hematopoietic stem cell or bone marrow transplantation Inclusion Criteria: - Confirmed EGFR mutation for non-small cell lung cancer associated with EGFR TKI sensitivity - For Part 2, EGFR T790M mutation-positive tumor status - Left ventricular ejection fraction (LVEF) ≥ institution's lower limit of the reference range - For Part 1, evaluable or measurable disease as defined by RECIST, Version 1.1 - For Part 2, measurable disease as defined by RECIST, Version 1.1 - ECOG performance status 0 to 1 - Adequate organ function Exclusion Criteria: - Prior treatment with EGFR TKI within 9 days of first study dose - For Part 1, prior treatment with more than 2 prior lines of chemotherapy for advanced NSCLC - For Part 2, prior treatment with osimertinib or other T790M active EGFR TKI - For Part 2, prior chemotherapy for advanced NSCLC - Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease - Investigational drug within 3 months or 5 half-lives, whichever is longer, of first study dose - Concurrent radiotherapy, radiotherapy within 28 days of first study dose, previous radiotherapy to the target lesion sites, or prior radiotherapy to > 25% of bone marrow - Prior hematopoietic stem cell or bone marrow transplantation Carcinoma, Non-Small-Cell Lung Lung Cancer Non-small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung null --- T790M --- --- T790M ---
Inclusion Criteria: - Confirmed EGFR mutation for non-small cell lung cancer associated with EGFR TKI sensitivity - For Part 2, EGFR T790M mutation-positive tumor status - Left ventricular ejection fraction (LVEF) ≥ institution's lower limit of the reference range - For Part 1, evaluable or measurable disease as defined by RECIST, Version 1.1 - For Part 2, measurable disease as defined by RECIST, Version 1.1 - ECOG performance status 0 to 1 - Adequate organ function Exclusion Criteria: - Prior treatment with EGFR TKI within 9 days of first study dose - For Part 1, prior treatment with more than 2 prior lines of chemotherapy for advanced NSCLC - For Part 2, prior treatment with osimertinib or other T790M active EGFR TKI - For Part 2, prior chemotherapy for advanced NSCLC - Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease - Investigational drug within 3 months or 5 half-lives, whichever is longer, of first study dose - Concurrent radiotherapy, radiotherapy within 28 days of first study dose, previous radiotherapy to the target lesion sites, or prior radiotherapy to > 25% of bone marrow - Prior hematopoietic stem cell or bone marrow transplantation Inclusion Criteria: - Confirmed EGFR mutation for non-small cell lung cancer associated with EGFR TKI sensitivity - For Part 2, EGFR T790M mutation-positive tumor status - Left ventricular ejection fraction (LVEF) ≥ institution's lower limit of the reference range - For Part 1, evaluable or measurable disease as defined by RECIST, Version 1.1 - For Part 2, measurable disease as defined by RECIST, Version 1.1 - ECOG performance status 0 to 1 - Adequate organ function Exclusion Criteria: - Prior treatment with EGFR TKI within 9 days of first study dose - For Part 1, prior treatment with more than 2 prior lines of chemotherapy for advanced NSCLC - For Part 2, prior treatment with osimertinib or other T790M active EGFR TKI - For Part 2, prior chemotherapy for advanced NSCLC - Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease - Investigational drug within 3 months or 5 half-lives, whichever is longer, of first study dose - Concurrent radiotherapy, radiotherapy within 28 days of first study dose, previous radiotherapy to the target lesion sites, or prior radiotherapy to > 25% of bone marrow - Prior hematopoietic stem cell or bone marrow transplantation Carcinoma, Non-Small-Cell Lung Lung Cancer Non-small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung null --- T790M --- --- T790M --- --- T790M ---
Inclusion Criteria: - Confirmed EGFR mutation for non-small cell lung cancer associated with EGFR TKI sensitivity - For Part 2, EGFR T790M mutation-positive tumor status - Left ventricular ejection fraction (LVEF) ≥ institution's lower limit of the reference range - For Part 1, evaluable or measurable disease as defined by RECIST, Version 1.1 - For Part 2, measurable disease as defined by RECIST, Version 1.1 - ECOG performance status 0 to 1 - Adequate organ function Exclusion Criteria: - Prior treatment with EGFR TKI within 9 days of first study dose - For Part 1, prior treatment with more than 2 prior lines of chemotherapy for advanced NSCLC - For Part 2, prior treatment with osimertinib or other T790M active EGFR TKI - For Part 2, prior chemotherapy for advanced NSCLC - Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease - Investigational drug within 3 months or 5 half-lives, whichever is longer, of first study dose - Concurrent radiotherapy, radiotherapy within 28 days of first study dose, previous radiotherapy to the target lesion sites, or prior radiotherapy to > 25% of bone marrow - Prior hematopoietic stem cell or bone marrow transplantation Inclusion Criteria: - Confirmed EGFR mutation for non-small cell lung cancer associated with EGFR TKI sensitivity - For Part 2, EGFR T790M mutation-positive tumor status - Left ventricular ejection fraction (LVEF) ≥ institution's lower limit of the reference range - For Part 1, evaluable or measurable disease as defined by RECIST, Version 1.1 - For Part 2, measurable disease as defined by RECIST, Version 1.1 - ECOG performance status 0 to 1 - Adequate organ function Exclusion Criteria: - Prior treatment with EGFR TKI within 9 days of first study dose - For Part 1, prior treatment with more than 2 prior lines of chemotherapy for advanced NSCLC - For Part 2, prior treatment with osimertinib or other T790M active EGFR TKI - For Part 2, prior chemotherapy for advanced NSCLC - Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease - Investigational drug within 3 months or 5 half-lives, whichever is longer, of first study dose - Concurrent radiotherapy, radiotherapy within 28 days of first study dose, previous radiotherapy to the target lesion sites, or prior radiotherapy to > 25% of bone marrow - Prior hematopoietic stem cell or bone marrow transplantation Carcinoma, Non-Small-Cell Lung Lung Cancer Non-small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung null --- T790M --- --- T790M --- --- T790M --- --- T790M ---