Clinical Trials /

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

NCT03455829

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: G1T38, a CDK 4/6 Inhibitor, in Combination With Osimertinib in EGFR-Mutant Non-Small Cell Lung Cancer
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: G1T38-03
  • SECONDARY ID: 2017-004315-39
  • NCT ID: NCT03455829

Conditions

  • Carcinoma, Non-Small-Cell Lung
  • Lung Cancer
  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
G1T38Part 1: G1T38 + Osimertinib
OsimertinibTagrissoPart 1: G1T38 + Osimertinib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Part 1: G1T38 + OsimertinibExperimentalPatients 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).
  • G1T38
  • Osimertinib
Part 2: G1T38 + OsimertinibExperimentalPatients will be randomized to receive G1T38 at the dose determined in Part 1 in combination with osimertinib 80 mg, each administered once-daily.
  • G1T38
  • Osimertinib
Part 2: OsimertinibActive ComparatorPatients will be randomized to receive osimertinib 80 mg once-daily. At the time of disease progression per RECIST v1.1, patients who were initially randomized to receive osimertinib alone may crossover to receive G1T38 + osimertinib.
  • Osimertinib

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicity
Time Frame:Cycle 1 Day -14 to Cycle 1 Day 28
Safety Issue:
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

Secondary Outcome Measures

Measure:Tumor response based on RECIST, Version 1.1
Time Frame:21 months
Safety Issue:
Description:
Measure: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.
Safety Issue:
Description:
Measure: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.
Safety Issue:
Description:
Measure: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.
Safety Issue:
Description:
Measure: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.
Safety Issue:
Description:
Measure:PFS using investigator assessment
Time Frame:36 months
Safety Issue:
Description:
Measure:1-year PFS using investigator assessment and BICR
Time Frame:33 months
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:60 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:G1 Therapeutics, Inc.

Trial Keywords

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

Last Updated

March 29, 2018