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)

Sierra Oncology

Status and phase

Terminated

Phase 1

Conditions

EGFR Mutated EGFR TKI Naive Metastatic NSCLC

Treatments

Drug: Erlotinib

Drug: Momelotinib (MMB)

Study type

Interventional

Funder types

Industry

Identifiers

NCT02206763

GS-US-370-1298

Details and patient eligibility

About

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.

Enrollment

11 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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/Exclusion criteria may apply.