Erlotinib and Momelotinib for the Treatment of Epidermal Growth Factor Receptor (EGFR) Mutated EGFR Tyrosine Kinase Inhibitor (TKI) Naive Metastatic Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1b Study of Erlotinib and Momelotinib for the Treatment of Epidermal Growth Factor Receptor (EGFR) Mutated EGFR Tyrosine Kinase Inhibitor (TKI) Naïve Metastatic Non-Small Cell Lung Cancer (NSCLC)

Conditions
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EGFR Mutated EGFR TKI Naive Metastatic NSCLC

Intervention / Treatment
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* Drug: Momelotinib (MMB)
* Drug: Erlotinib


Participation Criteria
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Eligibility Criteria
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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. History of interstitial pneumonitis Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Momelotinib (MMB)+erlotinib<br>Participants will receive momelotinib (MMB) plus erlotinib. | Drug: Momelotinib (MMB)<br>* Tablet(s) administered orally once or twice daily<br>* Other names: CYT387;Drug: Erlotinib<br>* Tablet(s) administered orally once daily.<br>* Other names: Tarceva®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Dose Limiting Toxicities (DLTs) | 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. | Up to 28 days | 
| Safety as Assessed by the Incidence of Adverse Events (AEs) |  | Up to 2 years plus 30 days | 
| Safety as Assessed by the Percentage of Participants Experiencing Treatment-Emergent Graded Lab Abnormalities (including Chemistry, Coagulation, Hematology, and Urinalysis) |  | Up to 2 years plus 30 days | 
| Change from Baseline in Vital Signs |  | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival | 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. | Until disease progression (up to 2 years) | 
| Overall Survival | Overall survival is defined as the interval from first dose date of study drug (MMB/erlotinib) to death from any cause. | Until disease progression (up to 2 years) | 
| Overall Response Rate | Overall response rate is defined as the proportion of participants who achieve a complete response or partial response. | Until disease progression (up to 2 years) | 
| Pharmacokinetic (PK) Parameter: Cmax of momelotinib (MMB) | Cmax is defined as the maximum observed concentration of drug. | Predose and up to 24 hours postdose | 
| PK Parameter: AUCtau of momelotinib (MMB) | AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). | Predose and up to 24 hours postdose | 
| PK Parameter: Cmax of Erlotinib | Cmax is defined as the maximum observed concentration of drug. | Predose and up to 24 hours postdose | 
| PK Parameter: AUCtau of Erlotinib | AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). | Predose and up to 24 hours postdose |