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)

NCT02206763 | Terminated Phase 1 FDA Drug

• 1 other identifier: GS-US-370-1298
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 3

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.

Conditions

EGFR Mutated EGFR TKI Naive Metastatic NSCLC

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (7)

• Progression-Free Survival

  Until disease progression (up to 2 years)

• Overall Survival

  Until disease progression (up to 2 years)

• Overall Response Rate

  Until disease progression (up to 2 years)

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

  Predose and up to 24 hours postdose

• PK Parameter: AUCtau of momelotinib (MMB)

  Predose and up to 24 hours postdose

Study Arms (1)

Momelotinib (MMB)+erlotinib

EXPERIMENTAL

Participants will receive momelotinib (MMB) plus erlotinib.

Drug: Momelotinib (MMB); Drug: Erlotinib

Interventions

Momelotinib (MMB) DRUG

Tablet(s) administered orally once or twice daily

Also known as: GS-0387, CYT387

Momelotinib (MMB)+erlotinib

Erlotinib DRUG

Tablet(s) administered orally once daily.

Also known as: Tarceva®

Momelotinib (MMB)+erlotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sierra Oncology LLC - a GSK company: lead

Study Sites (3)

Unknown Facility

Duarte, California, United States

Location

Unknown Facility

Palo Alto, California, United States

Location

Unknown Facility

Whittier, California, United States

Location

Related Publications (1)

• Padda SK, Reckamp KL, Koczywas M, Neal JW, Kawashima J, Kong S, Huang DB, Kowalski M, Wakelee HA. A phase 1b study of erlotinib and momelotinib for the treatment of EGFR-mutated, tyrosine kinase inhibitor-naive metastatic non-small cell lung cancer. Cancer Chemother Pharmacol. 2022 Jan;89(1):105-115. doi: 10.1007/s00280-021-04369-0. Epub 2021 Nov 13.

  PMID: 34773474 DERIVED

MeSH Terms

Interventions

N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide; Erlotinib Hydrochloride

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2014
• First Posted: August 1, 2014
• Study Start: October 16, 2014
• Primary Completion: January 12, 2017
• Study Completion: February 16, 2017
• Last Updated: February 1, 2019

Record last verified: 2019-01

Locations

US (3)