Osimertinib in Combination With Alisertib or Sapanisertib for the Treatment of Osimertinib-Resistant EGFR Mutant Stage IIIB or IV Non-Small Cell Lung Cancer

Recruiting in Palo Alto (17 mi)

Overseen byYasir Y Elamin, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: M.D. Anderson Cancer Center

No Placebo Group

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This phase Ib trial studies the best dose, safety, and effect of alisertib or sapanisertib, in combination with osimertinib, in treating patients with EGFR mutated stage IIIB or IV non-small cell lung cancer that does not respond to osimertinib treatment (osimertinib resistant). Osimertinib, alisertib, and sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This study has two parts. 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 safely 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.

Research Team

Yasir Y Elamin, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Inclusion Criteria

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). Eligible EGFR mutation must be confirmed by Clinical Laboratory Improvement Amendments (CLIA) certified test

Patients must have either a) disease progression on osimertinib within 30 days prior to study enrollment. Patients who continued osimertinib beyond disease progression (e.g. patients with oligo-progression who had radiation) may be eligible on further disease progression after discussion with principal investigator OR b) disease progression on osimertinib and one other line of systemic therapy (if the other systemic therapy line included PD-L1 blockade then the last dose of the latter must be more than 3 months prior to study enrollment). The number of patients who had prior osimertinib and other line of systemic therapy will be capped at 25% in each study arm

Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

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Treatment Details

Interventions

Alisertib (Protein Kinase Inhibitor)
Osimertinib (Protein Kinase Inhibitor)
Sapanisertib (Protein Kinase Inhibitor)

Participant Groups

2Treatment groups

Experimental Treatment

Group I: Arm B (osimertinib, sapanisertib)Experimental Treatment2 Interventions

Patients receive osimertinib PO QD on days 1-28 and sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who develop progressive disease may crossover to Arm A.

Group II: Arm A (osimertinib, alisertib)Experimental Treatment2 Interventions

Patients receive osimertinib PO QD on days 1-28 and alisertib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who develop progressive disease may crossover to Arm B.