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Report for Clinical Trial NCT02206763

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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.

NCT02206763 EGFR Mutated EGFR TKI Naive Metastatic NSCLC
MeSH: Carcinoma, Non-Small-Cell Lung
HPO: Non-small cell lung carcinoma

2 Interventions

Name: Momelotinib (MMB)

Description: Tablet(s) administered orally once or twice daily

Type: Drug

Momelotinib (MMB)+erlotinib

Name: Erlotinib

Description: Tablet(s) administered orally once daily.

Type: Drug

Momelotinib (MMB)+erlotinib


Primary Outcomes

Description: 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.

Measure: Incidence of Dose Limiting Toxicities (DLTs)

Time: Up to 28 days

Measure: Safety as Assessed by the Incidence of Adverse Events (AEs)

Time: 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)

Time: Up to 2 years plus 30 days

Measure: Change from Baseline in Vital Signs

Time: Up to 2 years

Secondary Outcomes

Description: 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.

Measure: Progression-Free Survival

Time: Until disease progression (up to 2 years)

Description: Overall survival is defined as the interval from first dose date of study drug (MMB/erlotinib) to death from any cause.

Measure: Overall Survival

Time: Until disease progression (up to 2 years)

Description: Overall response rate is defined as the proportion of participants who achieve a complete response or partial response.

Measure: Overall Response Rate

Time: Until disease progression (up to 2 years)

Description: Cmax is defined as the maximum observed concentration of drug.

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

Time: Predose and up to 24 hours postdose

Description: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Measure: PK Parameter: AUCtau of momelotinib (MMB)

Time: Predose and up to 24 hours postdose

Description: Cmax is defined as the maximum observed concentration of drug.

Measure: PK Parameter: Cmax of Erlotinib

Time: Predose and up to 24 hours postdose

Description: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Measure: PK Parameter: AUCtau of Erlotinib

Time: Predose and up to 24 hours postdose

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 L858R

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).. 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. --- L858R ---

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. --- L858R ---



HPO Nodes


HPO:
Non-small cell lung carcinoma
Genes 3
TP53 TP53 BAP1