Overview

This trial is active, not recruiting.

Condition relapsed metastatic kras-mutated non-small cell lung cancer
Treatments mmb, trametinib
Phase phase 1
Targets MEK, JAK, JAK1, JAK2
Sponsor Gilead Sciences
Start date March 2015
End date July 2016
Trial size 21 participants
Trial identifier NCT02258607, GS-US-370-1297

Summary

This study is conducted in two phases. The Dose-finding Lead-in Phase, Part A, will evaluate the safety and determine the maximum tolerated dose (MTD) of momelotinib (MMB) when combined with trametinib. Once the MTD of MMB is determined, the study will proceed to the Dose-finding Lead-in Phase, Part B, to determine the MTD of trametinib. After the MTD is established, the study may proceed to an expansion phase to determine the efficacy, safety, and tolerability of MMB combined with trametinib at the MTD in participants with kirsten rat sarcoma viral oncogene homolog (KRAS) mutated metastatic non-small cell lung cancer (NSCLC). Each treatment cycle will consist of 28 days and treatment will continue in the absence of disease progression, unacceptable toxicity, consent withdrawal, or participant's refusal of treatment.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants will receive MMB plus trametinib. MMB dose will increase to find the MTD.
mmb GS-0387
Momelotinib (MMB) tablet(s) administered orally once or twice daily
trametinib
Trametinib tablet administered orally once daily
(Experimental)
Participants will receive MMB plus trametinib. Trametinib dose will increase to find the MTD.
mmb GS-0387
Momelotinib (MMB) tablet(s) administered orally once or twice daily
trametinib
Trametinib tablet administered orally once daily
(Experimental)
Expansion Phase: participants will receive MMB plus trametinib for the duration of the study.
mmb GS-0387
Momelotinib (MMB) tablet(s) administered orally once or twice daily
trametinib
Trametinib tablet administered orally once daily

Primary Outcomes

Measure
For the Dose-finding Lead-in Phase, incidence of dose limiting toxicities (DLTs)
time frame: Up to 28 days
For Expansion Phase, disease control rate (DCR) at Week 8
time frame: Week 8

Secondary Outcomes

Measure
For the Dose-finding Lead-in Phase, disease control rate (DCR) at Week 8
time frame: Week 8
For the Dose-finding Lead-in Phase, overall survival
time frame: Up to 2 years
For the Dose-finding Lead-in Phase, progression free survival (PFS)
time frame: Up to 2 years
For the Dose-finding Lead-in Phase, overall response rate (ORR)
time frame: Up to 2 years
For the Dose-finding Lead-in Phase, plasma pharmacokinetics (PK) parameters of MMB and major metabolite GS-644603 as measured by Cmax and AUCtau
time frame: Days 1 and 15 (Cycle 1 only)
For Expansion Phase, overall survival
time frame: Up to 2 years
For Expansion Phase, progression free survival (PFS)
time frame: Up to 2 years
For Expansion Phase, overall response rate (ORR)
time frame: Up to 2 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Individuals with KRAS-mutated metastatic or recurrent non-small cell lung cancer - Radiologic documentation of disease progression - Measurable disease per RECIST v1.1 - Adequate organ function defined as follows: - Hepatic: Total conjugated bilirubin ≤ 1.25 x upper limit of normal (ULN); aspartate transaminase (AST) and alanine transaminase (ALT) < 3 x upper limit of normal (ULN) or < 5 x ULN in the setting of liver metastases - Hematological: Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, platelet ≥ 100 x 10^9/L, hemoglobin ≥ 9 g/dL - Renal: Serum creatinine < 1.5 x ULN OR calculated creatinine clearance (CLcr) ≥ 60 ml/min - Adequate left ventricular ejection fraction (LVEF) ≥ 50% - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 - Negative serum pregnancy test for females Exclusion Criteria: - Less than or equal to 3 weeks since receiving treatment with biologic, small molecule, chemotherapy or other agent for non-small cell lung cancer and 28 days since any prior immunotherapy (such as nivolumab) - History of a concurrent or second malignancy, except for specified exceptions in the protocol or any other cancer that has been in complete remission for ≥ 5 years - Known positive status for human immunodeficiency virus (HIV) - Chronic active or acute viral hepatitis A, B, or C infection or hepatitis B or C carrier - Presence of ≥ Grade 2 peripheral neuropathy - Brain metastases, or spinal cord compression. Individuals with brain metastases are allowed if they have been treated with irradiation or surgery, are clinically stable without steroid treatment. Individuals with documented leptomeningeal disease are not eligible. - A history of uveitis and/or scleritis - Retinal pathology beyond normal age-related processes - Evidence of a retinal vein occlusion on ophthalmological exam or a history of retinal vein occlusion - History of newly diagnosed or uncontrolled glaucoma/intraocular pressure > 21 mm Hg as measured by tonography - Use of daily and/or chronic oral or ocular steroids. Individuals must be off daily steroids for at least 3 weeks prior to enrolling into the trial - History of interstitial pneumonitis - History of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia method) at screening is prolonged (> 480 ms for males and females).

Additional Information

Official title A Phase 1b With Expansion Study Evaluating the Efficacy and Safety of Momelotinib Combined With Trametinib in Subjects With Metastatic KRAS-mutated Non-Small Cell Lung Cancer (NSCLC) Who Have Failed Platinum-Based Chemotherapy Preceded by a Dose-finding Lead-in Phase
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Gilead Sciences.
Location data was received from the National Cancer Institute and was last updated in August 2016.