Clinical trial NCT02206763: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: EGFR Mutated EGFR TKI Naive Metastatic NSCLC
Lead sponsor: Sierra Oncology LLC - a GSK company
Sponsor class: INDUSTRY
First posted: 2014-08-01
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities (DLTs)
timeFrame: Up to 28 days
measure: Safety as Assessed by the Incidence of Adverse Events (AEs)
timeFrame: Up to 2 years plus 30 days
measure: Safety as Assessed by the Percentage of Participants Experiencing Treatment-Emergent Graded Lab Abnormalities (including Chemistry, Coagulation, Hematology, and Urinalysis)
timeFrame: Up to 2 years plus 30 days
measure: Change from Baseline in Vital Signs
timeFrame: Up to 2 years
Secondary outcomes:
measure: Progression-Free Survival
timeFrame: Until disease progression (up to 2 years)
measure: Overall Survival
timeFrame: Until disease progression (up to 2 years)
measure: Overall Response Rate
timeFrame: Until disease progression (up to 2 years)
measure: Pharmacokinetic (PK) Parameter: Cmax of momelotinib (MMB)
timeFrame: Predose and up to 24 hours postdose
measure: PK Parameter: AUCtau of momelotinib (MMB)
timeFrame: Predose and up to 24 hours postdose
measure: PK Parameter: Cmax of Erlotinib
timeFrame: Predose and up to 24 hours postdose
measure: PK Parameter: AUCtau of Erlotinib
timeFrame: Predose and up to 24 hours postdose
Other outcomes:
Locations:
city: Duarte
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: Whittier
country: United States
state: California
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.