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)
- Conditions
- EGFR Mutated EGFR TKI Naive Metastatic NSCLC
- Interventions
- Registration Number
- NCT02206763
- Lead Sponsor
- Sierra Oncology LLC - a GSK company
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 11
-
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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Momelotinib (MMB)+erlotinib Momelotinib (MMB) Participants will receive momelotinib (MMB) plus erlotinib. Momelotinib (MMB)+erlotinib Erlotinib Participants will receive momelotinib (MMB) plus erlotinib.
- Primary Outcome Measures
Name Time Method Incidence of Dose Limiting Toxicities (DLTs) Up to 28 days 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.
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
Name Time Method Overall Response Rate Until disease progression (up to 2 years) Overall response rate is defined as the proportion of participants who achieve a complete response or partial response.
Progression-Free Survival Until disease progression (up to 2 years) 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.
Overall Survival Until disease progression (up to 2 years) Overall survival is defined as the interval from first dose date of study drug (MMB/erlotinib) to death from any cause.
Pharmacokinetic (PK) Parameter: Cmax of momelotinib (MMB) Predose and up to 24 hours postdose Cmax is defined as the maximum observed concentration of drug.
PK Parameter: AUCtau of momelotinib (MMB) Predose and up to 24 hours postdose AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter: Cmax of Erlotinib Predose and up to 24 hours postdose Cmax is defined as the maximum observed concentration of drug.
PK Parameter: AUCtau of Erlotinib Predose and up to 24 hours postdose AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).