This study will evaluate the safety, preliminary efficacy, and pharmacokinetics (PK) of momelotinib (MMB) and erlotinib, as well as define the maximum tolerated dose (MTD) of momelotinib (MMB) combined with erlotinib in adults with epidermal growth factor receptor (EGFR)-mutated, EGFR tyrosine kinase inhibitor (TKI) naive metastatic non-small cell lung cancer (NSCLC). Participants will be sequentially enrolled to receive progressively increasing doses of momelotinib (MMB) in combination with erlotinib. Escalation of momelotinib (MMB) doses will proceed to the MTD, defined as the highest tested dose associated with dose-limiting toxicities (DLT) during the first 28 days of combined erlotinib and momelotinib (MMB) treatment. There will be four dose levels and each treatment cycle will consist of 28 days.
Name: Momelotinib (MMB)
Description: Tablet(s) administered orally once or twice dailyType: DrugMomelotinib (MMB)+erlotinib
Name: Erlotinib
Description: Tablet(s) administered orally once daily.Type: DrugMomelotinib (MMB)+erlotinib
Description: Dose limiting toxicities refer to toxicities experienced during the first 28 days of combined erlotinib and momelotinib (MMB) treatment that have been judged to be clinically significant and related to study treatment.
Measure: Incidence of Dose Limiting Toxicities (DLTs) Time: Up to 28 daysDescription: Progression-free survival is defined as the interval from first dose date of study drug (MMB/erlotinib) to the earlier of the first documentation of definitive disease progression or death from any cause; definitive disease progression is progression based on RECIST criteria v1.1.
Measure: Progression-Free Survival Time: Until disease progression (up to 2 years)Description: Overall survival is defined as the interval from first dose date of study drug (MMB/erlotinib) to death from any cause.
Measure: Overall Survival Time: Until disease progression (up to 2 years)Description: Overall response rate is defined as the proportion of participants who achieve a complete response or partial response.
Measure: Overall Response Rate Time: Until disease progression (up to 2 years)Description: Cmax is defined as the maximum observed concentration of drug.
Measure: Pharmacokinetic (PK) Parameter: Cmax of momelotinib (MMB) Time: Predose and up to 24 hours postdoseDescription: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Measure: PK Parameter: AUCtau of momelotinib (MMB) Time: Predose and up to 24 hours postdoseDescription: Cmax is defined as the maximum observed concentration of drug.
Measure: PK Parameter: Cmax of Erlotinib Time: Predose and up to 24 hours postdoseDescription: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Measure: PK Parameter: AUCtau of Erlotinib Time: Predose and up to 24 hours postdoseSingle Group Assignment
There is one SNP
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).. Key Inclusion Criteria: - Metastatic NSCLC with documented EGFR exon 19 deletion or exon 21 (L858R) substitution mutation - Treatment naive OR one prior standard chemotherapy that is platinum-based - Adequate organ function defined as follows: - Hepatic: Total bilirubin < upper limit of the normal range (ULN); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN - Hematological: absolute neutrophil count (ANC) ≥1500 cells/mm^3, platelet ≥ 100,000 cells/mm^3, hemoglobin ≥ 9.0 g/dL - Renal: Serum creatinine < ULN OR calculated creatinine clearance (CLcr) of ≥ 60 ml/min - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 Key Exclusion Criteria: - Known positive status for human immunodeficiency virus (HIV) - Chronic active or acute viral hepatitis A, B, or C infection (testing required for hepatitis B and C) - Presence of > Grade 1 peripheral neuropathy - Symptomatic leptomeningeal, brain metastases, or spinal cord compression. --- L858R ---
Key Inclusion Criteria: - Metastatic NSCLC with documented EGFR exon 19 deletion or exon 21 (L858R) substitution mutation - Treatment naive OR one prior standard chemotherapy that is platinum-based - Adequate organ function defined as follows: - Hepatic: Total bilirubin < upper limit of the normal range (ULN); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN - Hematological: absolute neutrophil count (ANC) ≥1500 cells/mm^3, platelet ≥ 100,000 cells/mm^3, hemoglobin ≥ 9.0 g/dL - Renal: Serum creatinine < ULN OR calculated creatinine clearance (CLcr) of ≥ 60 ml/min - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 Key Exclusion Criteria: - Known positive status for human immunodeficiency virus (HIV) - Chronic active or acute viral hepatitis A, B, or C infection (testing required for hepatitis B and C) - Presence of > Grade 1 peripheral neuropathy - Symptomatic leptomeningeal, brain metastases, or spinal cord compression. --- L858R ---