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

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ClinicalTrials.gov Identifier: NCT03455829
Recruitment Status : Recruiting
First Posted : March 7, 2018
Last Update Posted : April 2, 2018
Sponsor:
Information provided by (Responsible Party):
G1 Therapeutics, Inc.

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
Carcinoma, Non-Small-Cell Lung Lung Cancer Non-small Cell Lung Cancer Drug: G1T38 Drug: Osimertinib Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 144 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 : March 29, 2018
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Osimertinib

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

Drug: Osimertinib
EGFR TKI; 80 mg
Other Name: 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

Drug: Osimertinib
EGFR TKI; 80 mg
Other Name: 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 Name: Tagrisso




Primary Outcome Measures :
  1. Dose Limiting Toxicity [ Time Frame: Cycle 1 Day -14 to Cycle 1 Day 28 ]
  2. Recommended Phase 2 dose [ Time Frame: 9 months ]
  3. Number of Treatment Related Adverse Event, including Abnormal Laboratory Events [ Time Frame: 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) [ Time Frame: 36 months ]

Secondary Outcome Measures :
  1. Tumor response based on RECIST, Version 1.1 [ Time Frame: 21 months ]
  2. 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. ]
  3. 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. ]
  4. 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. ]
  5. 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. ]
  6. PFS using investigator assessment [ Time Frame: 36 months ]
  7. 1-year PFS using investigator assessment and BICR [ Time Frame: 33 months ]
  8. Overall survival (OS) [ Time Frame: 60 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03455829


Contacts
Contact: G1 Therapeutics Clinical Contact 919-213-9835 clinicalinfo@g1therapeutics.com

Locations
United States, California
Beverly Hills Cancer Center Recruiting
Beverly Hills, California, United States, 90211
Principal Investigator: David Berz, MD         
St Joseph Heritage Healthcare Recruiting
Santa Rosa, California, United States, 95403
Contact: Ian Anderson, MD         
Sponsors and Collaborators
G1 Therapeutics, Inc.
Investigators
Study Director: Clinical Contact G1 Therapeutics, Inc.

Responsible Party: G1 Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03455829     History of Changes
Other Study ID Numbers: G1T38-03
2017-004315-39 ( EudraCT Number )
First Posted: March 7, 2018    Key Record Dates
Last Update Posted: April 2, 2018
Last Verified: March 2018

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

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action