EGFR Mutated EGFR TKI Naive Metastatic NSCLC
Conditions
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.
Interventions
Tablet(s) administered orally once or twice daily
DRUGErlotinib
Tablet(s) administered orally once daily.
Sponsors
Sierra Oncology LLC - a GSK company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
| 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). |
| PK Parameter: Cmax of Erlotinib | Predose and up to 24 hours postdose | Cmax is defined as the maximum observed concentration of drug. |
| 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. |
| 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. |
| Pharmacokinetic (PK) Parameter: Cmax of momelotinib (MMB) | Predose and up to 24 hours postdose | Cmax is defined as the maximum observed concentration of drug. |
Countries
United States
Outcome results
None listed