Alisertib in Combination With Osimertinib in Metastatic EGFR-mutant Lung Cancer
brief summary
This phase I/Ib trial studies the side effects and best dose of alisertib when given together with osimertinib in treating patients with EGFR-mutated stage IV lung cancer. Alisertib may stop the growth of tumor cells by blocking a specific protein (Aurora Kinase A) that researchers believe may be important for the growth of lung cancer. Osimertinib may reduce tumor growth by blocking the action of a certain mutant protein (EGFR). This study may help researchers test the safety of alisertib at different dose levels in combination with osimertinib, and to find out what effects, good and/or bad, it has on EGFR-mutated lung cancer.
detailed description
PRIMARY OBJECTIVE:
I. To determine the safety and tolerability of combination treatment with alisertib and osimertinib in patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC) who have progressed on osimertinib monotherapy and to identify a recommended phase 2 dose for the combination.
SECONDARY OBJECTIVES:
I. To provide preliminary efficacy data for the combination of alisertib and osimertinib in metastatic EGFR-mutant lung cancer patients who have progressed on osimertinib monotherapy.
II. To determine whether pre-treatment Targeting Protein for XKlp2 (TPX2) positivity by immunohistochemistry (IHC) correlates with response to alisertib + osimertinib combination therapy.
III. To evaluate the pharmacokinetics of alisertib in combination with osimertinib.
IV. To evaluate the central nervous system (CNS) response rate of alisertib + osimertinib.
V. To provide preliminary efficacy data for the combination of alisertib and osimertinib in metastatic EGFR-mutant lung cancer patients without known TP53 tumor genomic alterations who have progressed on osimertinib monotherapy.
EXPLORATORY (CORRELATIVE) OBJECTIVES:
I. To identify tumor co-occurring genomic alterations that correlate with response to alisertib + osimertinib treatment.
II. To determine whether phosphorylated (phospho)-aurora kinase A (AURKA) levels correlate with response to alisertib + osimertinib treatment.
III. To determine whether tumor nuclear factor kappa B (NF-κB) activity correlates with response to alisertib + osimertinib treatment.
IV. To evaluate for changes in circulating tumor deoxyribonucleic acid (ctDNA) during treatment with combination alisertib + osimertinib.
V. To identify mechanisms of resistance to alisertib + osimertinib.
VI. Safety in East Asian vs. Non-East Asian population.
VII. Pharmacokinetics in East Asian vs. Non-East Asian.
official title
A Phase I/Ib Study of Alisertib in Combination With Osimertinib in Metastatic EGFR-mutant Lung Cancer