Clinical trial NCT03455829: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: G1 Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-03-07
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Part 2, the Phase 2 part of the study, was not conducted due to changes in corporate strategy. There were no safety signals identified in Phase 1/Part 1 that would have precluded the conduct of Part 2. As a result, 30 out of the planned 144 patients were enrolled.

All tumor assessments were conducted by the Investigators or site radiologist. In order to reduce the burden to the patients, data of overall survival (OS) were no longer required (since 29 January 2020). No OS analysis was conducted for Part 1 due to limited data in Part 1.

PK data for Cohorts 4 (150 BID) and 5 (200 BID) were not analyzed as they were deemed unnecessary, as the PK data from Cohorts 1-3 were sufficient to achieve the secondary study objective of assessing the effect of osimertinib on PK parameters of G1T38.

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

Primary outcomes:
measure: Dose Limiting Toxicity
timeFrame: Cycle 1 Day -16 to Cycle 1 Day 28
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 36 months
measure: Best Overall Tumor Response
timeFrame: 21 months
measure: Pharmacokinetics of G1T38 and Metabolite G1T30: Maximum Plasma Concentration (Cmax)
timeFrame: Part 1, Cycle 1 Day -16 to Day -2.
measure: Pharmacokinetics of G1T38 and Metabolite G1T30: Area Under Curve - Plasma Concentration (AUC) Infinity
timeFrame: Part 1, Cycle 1 Day -16 to Day -2.
measure: Pharmacokinetics of G1T38 and Metabolite G1T30: Plasma: Terminal Half Life (T1/2)
timeFrame: Part 1, Cycle 1 Day -16 to Day -2.
measure: Pharmacokinetics of G1T38: Plasma - Volume of Distribution
timeFrame: Part 1, Cycle 1 Day -16 to Day -2.
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: Santa Monica
country: United States
facility: UCLA Medical Center, Division of Hematology/Oncology/Clinical Research Unit
state: California
city: Santa Rosa
country: United States
facility: St Joseph Heritage Healthcare
state: California
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center/University of Miami Miller School of Medicine Fox Building, Suite 200 G
state: Florida
city: Tampa
country: United States
facility: Mofitt Cancer Center
state: Florida
city: Ann Arbor
country: United States
facility: Univ. of Michigan Hospitals
state: Michigan
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Milwaukee
country: United States
facility: Froedtert Hospital & the Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: G1 Therapeutics, Inc.
name: Clinical Contact
role: STUDY_DIRECTOR
References: