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

Sponsor
G1 Therapeutics, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03455829
Collaborator
(none)
30
Enrollment
8
Locations
3
Arms
60.1
Anticipated Duration (Months)
3.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
30 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Mar 29, 2018
Actual Primary Completion Date :
Dec 14, 2021
Anticipated Study Completion Date :
Apr 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 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
CDK 4/6 inhibitor
Other Names:
  • Lerociclib

    • Drug: Osimertinib
    EGFR TKI; 80 mg
    Other Names:
  • Tagrisso

    		•
    Experimental: Part 2: G1T38 + Osimertinib

    Patients will be randomized to receive G1T38 at the dose determined in Part 1 in combination with osimertinib 80 mg, each administered once-daily.

    Drug: G1T38
    CDK 4/6 inhibitor
    Other Names:
  • Lerociclib

    • Drug: Osimertinib
    EGFR TKI; 80 mg
    Other Names:
  • Tagrisso

    		•
    Active Comparator: Part 2: Osimertinib

    Patients 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.

    Drug: Osimertinib
    EGFR TKI; 80 mg
    Other Names:
  • Tagrisso

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Dose Limiting Toxicity [Cycle 1 Day -14 to Cycle 1 Day 28]

    2. Recommended Phase 2 dose [9 months]

    3. Number of Treatment Related Adverse Event, including Abnormal Laboratory Events [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

    4. Progression free survival (PFS) using blinded independent central review (BICR) [36 months]

    Secondary Outcome Measures

    1. Tumor response based on RECIST, Version 1.1 [21 months]

    2. Pharmacokinetics of G1T38 and metabolite G1T30: Maximum Plasma Concentration (Cmax) [Part 1, Cycle 1 Day -14 to Day -2. Part 2, Cycle 1 Day 15 to Cycle 2 Day 1.]

    3. Pharmacokinetics of G1T38 and metabolite G1T30: Area under Curve - plasma concentration (AUC) [Part 1, Cycle 1 Day -14 to Day -2. Part 2, Cycle 1 Day 15 to Cycle 2 Day 1.]

    4. Pharmacokinetics of G1T38 and metabolite G1T30: Plasma: terminal half life (T1/2) [Part 1, Cycle 1 Day -14 to Day -2. Part 2, Cycle 1 Day 15 to Cycle 2 Day 1.]

    5. Pharmacokinetics of G1T38 and metabolite G1T30: Plasma - Volume of distribution [Part 1, Cycle 1 Day -14 to Day -2. Part 2, Cycle 1 Day 15 to Cycle 2 Day 1.]

    6. PFS using investigator assessment [36 months]

    7. 1-year PFS using investigator assessment and BICR [33 months]

    8. Overall survival (OS) [60 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Beverly Hills Cancer Center Beverly Hills California United States 90211
    2 UCLA Medical Center, Division of Hematology/Oncology/Clinical Research Unit Santa Monica California United States 90404
    3 St Joseph Heritage Healthcare Santa Rosa California United States 95403
    4 Sylvester Comprehensive Cancer Center/University of Miami Miller School of Medicine Fox Building, Suite 200 G Miami Florida United States 33136
    5 Mofitt Cancer Center Tampa Florida United States 33612
    6 Univ. of Michigan Hospitals Ann Arbor Michigan United States 48109
    7 Virginia Cancer Specialists Fairfax Virginia United States 22301
    8 Froedtert Hospital & the Medical College of Wisconsin Milwaukee Wisconsin United States 53226

    Sponsors and Collaborators

    • G1 Therapeutics, Inc.

    Investigators

    • Study Director: Clinical Contact, G1 Therapeutics, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    G1 Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT03455829
    Other Study ID Numbers:
    • G1T38-03
    • 2017-004315-39
    First Posted:
    Mar 7, 2018
    Last Update Posted:
    Jan 27, 2022
    Last Verified:
    Jan 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by G1 Therapeutics, Inc.
    Lung Cancer
    Non-small Cell Lung Cancer
    CDK 4/6 Inhibitor
    EGFR-Positive
    EGFR Mutation- Positive
    T790M
    EGFR Mutant
    lerociclib
    Additional relevant MeSH terms:
    Lung Neoplasms
    Carcinoma, Non-Small-Cell Lung
    Osimertinib

    Study Results

    No Results Posted as of Jan 27, 2022