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)

A Phase 1b Study of Erlotinib and Momelotinib for the Treatment of Epidermal Growth Factor Receptor (EGFR) Mutated EGFR Tyrosine Kinase Inhibitor (TKI) Naïve Metastatic Non-Small Cell Lung Cancer (NSCLC)

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 Overview

• Status: Terminated
• Conditions: EGFR Mutated EGFR TKI Naive Metastatic NSCLC
• Intervention / Treatment: Drug: Momelotinib (MMB); Drug: Erlotinib

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States
    • Palo Alto, California, United States
    • Whittier, California, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Momelotinib (MMB)+erlotinib; Participants will receive momelotinib (MMB) plus erlotinib.	Drug: Momelotinib (MMB); Tablet(s) administered orally once or twice daily; Other Names: GS-0387; CYT387; Drug: Erlotinib; Tablet(s) administered orally once daily.; Other Names: Tarceva®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	Until disease progression (up to 2 years)
Pharmacokinetic (PK) Parameter: Cmax of momelotinib (MMB)	Cmax is defined as the maximum observed concentration of drug.	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).	Predose and up to 24 hours postdose
PK Parameter: Cmax of Erlotinib	Cmax is defined as the maximum observed concentration of drug.	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).	Predose and up to 24 hours postdose

Collaborators and Investigators

• Sponsor: Sierra Oncology, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2014
• Primary Completion (Actual): January 12, 2017
• Study Completion (Actual): February 16, 2017

Study Registration Dates

• First Submitted: July 30, 2014
• First Submitted That Met QC Criteria: July 30, 2014
• First Posted (Estimate): August 1, 2014

Study Record Updates

• Last Update Posted (Actual): February 1, 2019
• Last Update Submitted That Met QC Criteria: January 30, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride; N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide
• Other Study ID Numbers: GS-US-370-1298

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No