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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
21
Momelotinib (MMB) tablet(s) administered orally once or twice daily
Trametinib tablet administered orally once daily
Unnamed facility
Duarte, California, United States
Unnamed facility
Sacramento, California, United States
Unnamed facility
Boston, Massachusetts, United States
Unnamed facility
Fairfax, Virginia, United States
Unnamed facility
Spokane, Washington, United States
For the Dose-finding Lead-in Phase, incidence of dose limiting toxicities (DLTs)
Dose limiting toxicities (DLTs) refer to toxicities experienced during the first 28 days of treatment that have been judged to be clinically significant and at least possibly related to study treatment.
Time frame: Up to 28 days
For Expansion Phase, disease control rate (DCR) at Week 8
Disease control rate (DCR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) or stable disease (SD) as assessed by Response Evaluation Criteria In Solid Tumor (RECIST) v1.1.
Time frame: Week 8
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
Overall survival is defined as the interval from first dose of study drug to death from any cause.
Time frame: Up to 2 years
For the Dose-finding Lead-in Phase, progression free survival (PFS)
Progression free survival (PFS) is defined as the interval from first dose date of study drug to the earlier of the first documentation of definitive disease progression or death from any cause.
Time frame: Up to 2 years
For the Dose-finding Lead-in Phase, overall response rate (ORR)
Overall response rate (ORR) is defined as the proportion of participants who achieve a CR or PR as assessed by RECIST v1.1.
Time frame: Up to 2 years
For the Dose-finding Lead-in Phase, plasma pharmacokinetics (PK) parameters of momelotinib (MMB) and major metabolite GS-644603 as measured by Cmax and AUCtau
This composite endpoint will measure the plasma PK profile of momelotinib (MMB) and GS-644603. The following parameters will be measured: * Cmax: maximum observed concentration of drug in plasma * AUCtau: concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
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
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