Description:
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.
<span class="go-doc-concept go-doc-intervention">Erlotinib</span> and Momelotinib for the Treatment of Epidermal Growth Factor Receptor (<span class="go-doc-concept go-doc-biomarker">EGFR</span>) <span class="go-doc-concept go-doc-keyword">Mutated</span> <span class="go-doc-concept go-doc-biomarker">EGFR</span> <span class="go-doc-concept go-doc-intervention">Tyrosine Kinase Inhibitor</span> (<span class="go-doc-concept go-doc-intervention">TKI</span>) Naive Metastatic Non-Small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span> (NSCLC)
Title
Brief Title: 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) Nave Metastatic Non-Small Cell Lung Cancer (NSCLC)
Clinical Trial IDs
NCT ID: NCT02206763
ORG ID: GS-US-370-1298
Trial Conditions
EGFR Mutated EGFR TKI Nave Metastatic NSCLC
Trial Interventions
Drug |
Synonyms |
Arms |
MMB |
GS-0387, CYT387 |
Dose Escalation Phase, MMB+erlotinib, Dose Expansion Phase, MMB+erlotinib |
Erlotinib |
|
Dose Escalation Phase, MMB+erlotinib, Dose Expansion Phase, MMB+erlotinib, Dose Expansion Phase, erlotinib |
Trial Purpose
There will be two parts to this study. The dose escalation phase 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). During this phase, participants
will be sequentially enrolled to receive progressively increasing doses of MMB in
combination with erlotinib. Escalation of 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 MMB treatment. There will be four dose levels and each treatment
cycle will consist of 28 days.
The dose expansion phase will evaluate the efficacy, safety, and tolerability of erlotinib
combined with MMB administered at the MTD versus erlotinib alone in adults with EGFR-Mutated
EGFR TKI naive metastatic NSCLC.
Detailed Description
Trial Arms
Name |
Type |
Description |
Interventions |
Dose Escalation Phase, MMB+erlotinib |
Experimental |
Participants will receive MMB and erlotinib. |
MMB, Erlotinib |
Dose Expansion Phase, MMB+erlotinib |
Experimental |
Participants will receive MMB and erlotinib. |
MMB, Erlotinib |
Dose Expansion Phase, erlotinib |
Experimental |
Participants will receive erlotinib alone. |
Erlotinib |
Eligibility Criteria
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 (CrCl) of 60
ml/min
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
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
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
Primary Outcome Measures
During the dose escalation phase, incidence of dose limiting toxicities (DLTs)
During the dose expansion phase, progression free survival
Secondary Outcome Measures
During the dose escalation phase, progression free survival
During the dose escalation phase, overall survival
During the dose escalation phase, overall response rate
During the dose escalation phase, PK profile of MMB
During the dose escalation phase, PK profile of erlotinib
During the dose expansion phase, overall survival
During the dose expansion phase, overall response rate
During the dose expansion phase, PK profile of MMB trough as measured by standardized PK methodology
Trial Keywords