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

NCT03455829 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: G1T38-032017-004315-39
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 8

Brief Summary

This was 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 was an open-label design, planned to consist of 2 parts: a safety, pharmacokinetic, and dose-finding portion (Part 1), and a randomized portion (Part 2). Both parts were to include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase began on the day of first dose with study treatment and completes at the Post-Treatment Visit. Approximately, 144 patients were planned to be enrolled in the study.

Conditions

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

Keywords

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

Outcome Measures

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).

  Cycle 1 Day -16 to Cycle 1 Day 28

Secondary Outcomes (6)

• Progression Free Survival (PFS)

  36 months

• Best Overall Tumor Response

  21 months

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

  Part 1, Cycle 1 Day -16 to Day -2.

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

  Part 1, Cycle 1 Day -16 to Day -2.

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

  Part 1, Cycle 1 Day -16 to Day -2.

Study Arms (5)

Part 1: Cohort 1 G1T38 + Osimertinib

EXPERIMENTAL

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

Part 1: Cohort 2 G1T38 + Osimertinib

EXPERIMENTAL

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

Part 1: Cohort 3 G1T38 + Osimertinib

EXPERIMENTAL

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

Part 1: Cohort 4 G1T38 + Osimertinib

EXPERIMENTAL

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

Part 1: Cohort 5 G1T38 + Osimertinib

EXPERIMENTAL

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

G1T38 DRUG

CDK 4/6 inhibitor

Also known as: Lerociclib

Part 1: Cohort 1 G1T38 + Osimertinib; Part 1: Cohort 2 G1T38 + Osimertinib; Part 1: Cohort 3 G1T38 + Osimertinib; Part 1: Cohort 4 G1T38 + Osimertinib; Part 1: Cohort 5 G1T38 + Osimertinib

Osimertinib DRUG

EGFR TKI; 80 mg

Also known as: Tagrisso

Part 1: Cohort 1 G1T38 + Osimertinib; Part 1: Cohort 2 G1T38 + Osimertinib; Part 1: Cohort 3 G1T38 + Osimertinib; Part 1: Cohort 4 G1T38 + Osimertinib; Part 1: Cohort 5 G1T38 + Osimertinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• G1 Therapeutics, Inc.: lead

Study Sites (8)

Beverly Hills Cancer Center

Beverly Hills, California, 90211, United States

Location

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

Santa Monica, California, 90404, United States

Location

St Joseph Heritage Healthcare

Santa Rosa, California, 95403, United States

Location

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

Miami, Florida, 33136, United States

Location

Mofitt Cancer Center

Tampa, Florida, 33612, United States

Location

Univ. of Michigan Hospitals

Ann Arbor, Michigan, 48109, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22301, United States

Location

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

A limitation of the trial is small numbers of subjects, since only the Phase 1/Part 1 part of the trial was conducted. A lack of a control group, blinding and randomization also limits the utility of the information, so it is difficult to determine if there is any change in safety or tolerability of the combination of G1T38 + osimertinib from that of osimertinib alone or if there was any selection bias introduced.

Results Point of Contact

• Title: Clinical Trial Info.
• Organization: G1 Therapeutics, Inc.

clinicalinfo@g1therapeutics.com

919-213-9835

Study Officials

• Clinical Contact

  G1 Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2018
• First Posted: March 7, 2018
• Study Start: March 29, 2018
• Primary Completion: December 14, 2021
• Study Completion: February 14, 2022
• Last Updated: May 6, 2023
• Results First Posted: May 1, 2023

Record last verified: 2023-05

Locations

US (8)