G1T38, a CDK 4/6 Inhibitor, in Combination With Osimertinib in EGFR-Mutant Non-Small Cell Lung Cancer

The percentage of patients experiencing DLTs in Part 1 of the study in each cohort, including: * Grade 4 neutropenia * ≥ Grade 3 neutropenic infection/febrile neutropenia * Grade 4 thrombocytopenia * ≥ Grade 3 thrombocytopenia with bleeding * ≥ Grade 3 nonhematologic toxicity (additional criteria for nausea, vomiting, diarrhea, or fatigue: lasting \> 5 days with maximal medical management) * Liver function test abnormalities meeting Hy's Law criteria (aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\] ≥ 3 × upper limit of normal \[ULN\] and total bilirubin ≥ 2 × ULN).

Time frame: Cycle 1 Day -16 to Cycle 1 Day 28

Population: Safety analysis set: including all enrolled patients who were administered at least 1 dose of study drug.

The percentage of patients who fall into each category of Best overall response (BOR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 guidelines. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. When no imaging/measurement is done, the patient is not evaluable (NE); and if only a subset of lesion measurements are made, usually the case is also considered NE.

Time frame: 21 months

Population: The response evaluable analysis set includes all patients who received study drug, had a measurable lesion (target lesions) at the baseline tumor assessment, and either (i) had at least 1 post-baseline tumor assessment, or (ii) did not have a post-baseline tumor assessment but had clinical progression as noted by the investigator, or died due to disease progression before their first post-baseline tumor scan.

Area under the concentration-time curve from time zero extrapolated to infinity using the linear-up log-down trapezoidal rule.

Time frame: Part 1, Cycle 1 Day -16 to Day -2.

Population: The analysis population included only those patients that received G1T38 on a once daily schedule, that is Cohorts 1-3. Pharmacokinetic data for Cohorts 4 and 5 were not collected due to the twice daily dosing schedule implemented, per recommendation of the Safety Monitoring Committee, for these 2 cohorts.

The observed peak plasma concentration determined from the plasma concentration versus time data.

Time frame: Part 1, Cycle 1 Day -16 to Day -2.

Population: The analysis population included only those patients that received G1T38 on a once daily schedule, that is Cohorts 1-3. Pharmacokinetic data for Cohorts 4 and 5 were not collected due to the twice daily dosing schedule implemented, per recommendation of the Safety Monitoring Committee, for these 2 cohorts.

Terminal half-life, defined as 0.693 divided by the terminal phase rate constant by λz , determined by linear regression of at least 3 points on the terminal phase of the log-linear plasma concentration-time curve.

Time frame: Part 1, Cycle 1 Day -16 to Day -2.

Population: The analysis population included only those patients that received G1T38 on a once daily schedule, that is Cohorts 1-3. Pharmacokinetic data for Cohorts 4 and 5 were not collected due to the twice daily dosing schedule implemented, per recommendation of the Safety Monitoring Committee, for these 2 cohorts.

Volume of distribution in the terminal elimination phase, calculated as: Vz/F = (CL/F)/λz

Time frame: Part 1, Cycle 1 Day -16 to Day -2.

Population: The analysis population included only those patients that received G1T38 on a once daily schedule, that is Cohorts 1-3. Pharmacokinetic data for Cohorts 4 and 5 were not collected due to the twice daily dosing schedule implemented, per recommendation of the Safety Monitoring Committee, for these 2 cohorts.

Median time (months) and 95% CI from date of first dose of study drug/randomization until date of documented disease progression or death due to any cause. Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 guidelines for tumor assessments were used to determine progression. Progressive Disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

Time frame: 36 months

Population: Full Analysis Set: All enrolled patients who were administered at least one dose of continuous daily G1T38.