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)

Phase 1TerminatedNCT02206763

Sierra Oncology LLC - a GSK company11 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

EGFR Mutated EGFR TKI Naive Metastatic NSCLC

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (3)

Unnamed facility

Duarte, California, United States

Unnamed facility

Palo Alto, California, United States

Unnamed facility

Whittier, California, United States

Outcomes

Primary Outcomes

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.

Time frame: Up to 28 days

Safety as Assessed by the Incidence of Adverse Events (AEs)

Time frame: 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)

Time frame: Up to 2 years plus 30 days

Change from Baseline in Vital Signs

Time frame: Up to 2 years

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Until disease progression (up to 2 years)

Pharmacokinetic (PK) Parameter: Cmax of momelotinib (MMB)

Cmax is defined as the maximum observed concentration of drug.

Time frame: 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).

Time frame: Predose and up to 24 hours postdose

PK Parameter: Cmax of Erlotinib

Cmax is defined as the maximum observed concentration of drug.

Time frame: 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).

Time frame: Predose and up to 24 hours postdose