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

• ClinicalTrials.gov Identifier: NCT03455829
• Recruitment Status: Completed
• First Posted: March 7, 2018
• Last Update Posted: September 22, 2022
• Sponsor: G1 Therapeutics, Inc.
• Information provided by (Responsible Party): G1 Therapeutics, Inc.

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

Study Design

• Study Type: Interventional (Clinical Trial)
• 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: March 29, 2018
• Actual Primary Completion Date: December 14, 2021
• Actual Study Completion Date: February 14, 2022

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 Name: Lerociclib; 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; Other Name: Lerociclib; 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

Outcome Measures

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 ]

Eligibility Criteria

• 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

Contacts and Locations

Locations

United States, California

Beverly Hills Cancer Center

Beverly Hills, California, United States, 90211

UCLA Medical Center, Division of Hematology/Oncology/Clinical Research Unit

Santa Monica, California, United States, 90404

St Joseph Heritage Healthcare

Santa Rosa, California, United States, 95403

United States, Florida

Sylvester Comprehensive Cancer Center/University of Miami Miller School of Medicine Fox Building, Suite 200 G

Miami, Florida, United States, 33136

Mofitt Cancer Center

Tampa, Florida, United States, 33612

United States, Michigan

Univ. of Michigan Hospitals

Ann Arbor, Michigan, United States, 48109

United States, Virginia

Virginia Cancer Specialists

Fairfax, Virginia, United States, 22301

United States, Wisconsin

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.

More Information

• Responsible Party: G1 Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03455829
• Other Study ID Numbers: G1T38-03; 2017-004315-39 ( EudraCT Number )
• First Posted: March 7, 2018
• Last Update Posted: September 22, 2022
• Last Verified: September 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; 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