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

Browse trials for

• Lung Neoplasms 7,233
• Carcinoma, Non-Small-Cell Lung 6,475

Keywords

• Lung Cancer
• Non-small Cell Lung Cancer
• CDK 4/6 Inhibitor
• EGFR-Positive
• EGFR Mutation- Positive
• T790M
• EGFR Mutant
• lerociclib

Study arms

• Experimental
  Part 1: Cohort 1 G1T38 + Osimertinib

  Patients will receive a single oral dose of G1T38 on Cycle 1 Day -16 and on Cycle 1 Day -2. Patients will receive oral osimertinib 80 mg beginning Cycle 1 Days -14. Patients will begin G1T38 once-daily dosing on Cycle 1 Day 1 (in combination with osimertinib 80 mg).

  Drug: G1T38 · Drug: Osimertinib

• Experimental
  Part 1: Cohort 2 G1T38 + Osimertinib

  Patients will receive a single oral dose of G1T38 on Cycle 1 Day -16 and on Cycle 1 Day -2. Patients will receive oral osimertinib 80 mg beginning Cycle 1 Days -14. Patients will begin G1T38 once-daily dosing on Cycle 1 Day 1 (in combination with osimertinib 80 mg).

  Drug: G1T38 · Drug: Osimertinib

• Experimental
  Part 1: Cohort 3 G1T38 + Osimertinib

  Patients will receive a single oral dose of G1T38 on Cycle 1 Day -16 and on Cycle 1 Day -2. Patients will receive oral osimertinib 80 mg beginning Cycle 1 Days -14. Patients will begin G1T38 once-daily dosing on Cycle 1 Day 1 (in combination with osimertinib 80 mg).

  Drug: G1T38 · Drug: Osimertinib

• Experimental
  Part 1: Cohort 4 G1T38 + Osimertinib

  Patients will receive a single oral dose of G1T38 on Cycle 1 Day -16 and on Cycle 1 Day -2. Patients will receive oral osimertinib 80 mg beginning Cycle 1 Days -14. Patients will begin G1T38 once-daily dosing on Cycle 1 Day 1 (in combination with osimertinib 80 mg).

  Drug: G1T38 · Drug: Osimertinib

• Experimental
  Part 1: Cohort 5 G1T38 + Osimertinib

  Patients will receive a single oral dose of G1T38 on Cycle 1 Day -16 and on Cycle 1 Day -2. Patients will receive oral osimertinib 80 mg beginning Cycle 1 Days -14. Patients will begin G1T38 once-daily dosing on Cycle 1 Day 1 (in combination with osimertinib 80 mg).

  Drug: G1T38 · Drug: Osimertinib

Interventions

• DrugG1T38

  CDK 4/6 inhibitor

  Also known as: Lerociclib

• DrugOsimertinib

  EGFR TKI; 80 mg

  Also known as: Tagrisso

Primary outcomes

1. Dose Limiting Toxicity

   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

Secondary outcomes

1. Progression Free Survival (PFS)

   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

2. Best Overall Tumor Response

   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

3. Pharmacokinetics of G1T38 and Metabolite G1T30: Maximum Plasma Concentration (Cmax)

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

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

4. Pharmacokinetics of G1T38 and Metabolite G1T30: Area Under Curve - Plasma Concentration (AUC) Infinity

   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.

5. Pharmacokinetics of G1T38 and Metabolite G1T30: Plasma: Terminal Half Life (T1/2)

   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.

6. Pharmacokinetics of G1T38: Plasma - Volume of Distribution

   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.

Baseline characteristics

Study documents

• Study protocol · Sep 2, 2019
• Statistical analysis plan · Feb 10, 2021

Documents are hosted by the registry — open the source record to download them.