Lung Cancer Clinical Trial
Efficacy and Safety of Momelotinib Combined With Trametinib in Adults With Metastatic KRAS-mutated Non-Small Cell Lung Cancer (NSCLC) Who Have Failed Platinum-Based Chemotherapy Preceded by a Dose-finding Lead-in Phase
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 momelotinib (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.
Key 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
Key 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)
Note: Other protocol defined Inclusion/Exclusion criteria may apply
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There is 1 Location for this study
Duarte California, , United States
Sacramento California, , United States
Boston Massachusetts, , United States
Fairfax Virginia, , United States
Spokane Washington, , United States
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