This phase Ib trial studies the side effects and best dose of alisertib or sapanisertib, in combination with osimertinib, in treating patients with EGFR mutated stage IIIB or IV non-small cell lung cancer that remains despite treatment with osimertinib (osimertinib resistant). Osimertinib, alisertib, and sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The goal of part 1 of this trial is to find the highest tolerable dose of alisertib or sapanisertib in combination with osimertinib that can be given to patients with EGFR mutated non-small cell lung cancer. The goal of part 2 of this trial is to learn if the dose of alisertib or sapanisertib found in part 1 can help control EGFR mutated non-small cell lung cancer when given in combination with osimertinib.
Name: Alisertib
Name: Osimertinib
Name: Sapanisertib
Description: Will employ the Bayesian optimal interval (BOIN) design to find the maximum tolerated dose (MTD) in each treatment arm. RP2D will be the same as the MTD or a lower dose level if pharmacokinetic/pharmacodynamics data indicate that the lower dose level can be as efficacious with possible lower toxicities
Measure: Recommended phase 2 dose (RP2D) of osimertinib and alisertib combination (Arm A) Time: Up to 30 daysDescription: Will employ the BOIN design to find the MTD in each treatment arm. RP2D will be the same as the MTD or a lower dose level if pharmacokinetic/pharmacodynamics data indicate that the lower dose level can be as efficacious with possible lower toxicities
Measure: RP2D of osimertinib and sapanisertib combination (Arm B) Time: Up to 30 daysDescription: Toxicity will be evaluated according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Will be estimated with 95% confidence intervals.
Measure: Incidence of adverse events Time: Up to 30 days after last doseDescription: Will be estimated with 95% confidence intervals.
Measure: Objective response rate Time: At end of 4th cycle (1 cycle = 28 days)Description: Estimated using the method of Kaplan and Meier.
Measure: Progression-free survival Time: Up to 30 days after last doseAllocation: Non-Randomized
Crossover Assignment
There are 2 SNPs
Estimated using the method of Kaplan and Meier.. Inclusion Criteria: - Patients must have histologically or cytologically confirmed non-small cell lung cancer - Stage IIIB/IV or recurrent non-small cell lung cancer which is not amenable to curative intent therapy - EGFR exon 21 L858R or exon 19 deletion mutation, or T790M mutation that was acquired following treatment with first or second generation tyrosine kinase inhibitor (TKI). --- L858R ---
- Female patient who intend to donate eggs (ova) during the course of this study or 180 days after receiving their last dose of study drug(s) - Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s) Inclusion Criteria: - Patients must have histologically or cytologically confirmed non-small cell lung cancer - Stage IIIB/IV or recurrent non-small cell lung cancer which is not amenable to curative intent therapy - EGFR exon 21 L858R or exon 19 deletion mutation, or T790M mutation that was acquired following treatment with first or second generation tyrosine kinase inhibitor (TKI). --- L858R ---
Estimated using the method of Kaplan and Meier.. Inclusion Criteria: - Patients must have histologically or cytologically confirmed non-small cell lung cancer - Stage IIIB/IV or recurrent non-small cell lung cancer which is not amenable to curative intent therapy - EGFR exon 21 L858R or exon 19 deletion mutation, or T790M mutation that was acquired following treatment with first or second generation tyrosine kinase inhibitor (TKI). --- L858R --- --- T790M ---
- Female patient who intend to donate eggs (ova) during the course of this study or 180 days after receiving their last dose of study drug(s) - Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s) Inclusion Criteria: - Patients must have histologically or cytologically confirmed non-small cell lung cancer - Stage IIIB/IV or recurrent non-small cell lung cancer which is not amenable to curative intent therapy - EGFR exon 21 L858R or exon 19 deletion mutation, or T790M mutation that was acquired following treatment with first or second generation tyrosine kinase inhibitor (TKI). --- L858R --- --- T790M ---
- Female patient who intend to donate eggs (ova) during the course of this study or 180 days after receiving their last dose of study drug(s) - Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s) EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma Recurrent Lung Non-Small Cell Carcinoma Stage IIIB Lung Cancer AJCC v8 Stage IV Lung Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8 Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung PRIMARY OBJECTIVES: I. Determine the safety and the recommended phase 2 dose (RP2D) of osimertinib plus alisertib II. --- T790M ---