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

NCT04479306 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2019-1196NCI-2020-05282
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Stage IIIB Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Recurrent Lung Non-Small Cell Carcinoma; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (4)

• Recommended phase 2 dose (RP2D) of osimertinib and alisertib combination (Arm A)

  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.

  Up to 30 days after the last dose

• RP2D of osimertinib and sapanisertib combination (Arm B)

  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.

  Up to 30 days

• Dose-limiting toxicity (DLT)

  During cycle 1 (28 days)

• Incidence of adverse events

  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.

  Up to 30 days after the last dose

Secondary Outcomes (2)

• Objective response rate

  At end of 4th cycle (1 cycle = 28 days)

• Progression-free survival

  Up to 30 days after last dose

Study Arms (2)

Arm A (osimertinib, alisertib)

EXPERIMENTAL

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.

Drug: Alisertib; Drug: Osimertinib

Arm B (osimertinib, sapanisertib)

EXPERIMENTAL

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.

Drug: Osimertinib; Drug: Sapanisertib

Interventions

Alisertib DRUG

Given PO

Also known as: Aurora A Kinase Inhibitor MLN8237, MLN-8237, MLN8237

Arm A (osimertinib, alisertib)

Osimertinib DRUG

Given PO

Also known as: AZD-9291, AZD9291, Mereletinib, Tagrisso

Arm A (osimertinib, alisertib); Arm B (osimertinib, sapanisertib)

Sapanisertib DRUG

Given PO

Also known as: INK-128, INK128, MLN-0128, MLN0128, TAK-228

Arm B (osimertinib, sapanisertib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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). 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
• Local ablative therapy (e.g. stereotactic radiosurgery \[SRS\], stereotactic body radiation therapy \[SBRT\], or surgery) for brain or systemic metastases prior to enrollment is allowed
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Absolute neutrophil count (ANC) \> 1500/ mm\^3 (within 28 days before the first dose of study drug)
• Platelets \> 100,000/mm\^3 (within 28 days before the first dose of study drug)
• Hemoglobin \> 9 g/dL. Values must be obtained without need for myeloid growth factor or transfusion support within 14 days, however, erythrocyte growth factor is allowed as per published American Society of Clinical Oncology (ASCO) guidelines (within 28 days before the first dose of study drug)
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (within 28 days before the first dose of study drug)
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) and serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 2.5 x ULN (may be up to 5 x ULN if with known liver metastases \[mets\]) (within 28 days before the first dose of study drug)
• ALISERTIB ARM: Creatinine clearance (Cockcroft-Gault Formula) \>= 30 ml/min (within 28 days before the first dose of study drug)
• SAPANISERTIB ARM: Creatinine clearance (Cockcroft-Gault Formula) \>= 60 ml/min (within 28 days before the first dose of study drug)
• SAPANISERTIB ARM: Glycosylated hemoglobin (HbA1c) \< 7.0% (within 28 days before the first dose of study drug)

You may not qualify if:

• ALISERTIB ARM: Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%
• ALISERTIB ARM: Prior allogeneic bone marrow or organ transplantation
• Known gastrointestinal (GI) disease or GI procedures that could interfere with the oral absorption or tolerance of study drugs. Examples include, but are not limited to partial gastrectomy, history of small intestine surgery, and celiac disease. In addition, patients with enteric stomata are also excluded
• Inability to swallow oral medication or inability or unwillingness to comply with the administration requirements related to study drugs
• ALISERTIB ARM: Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen
• Requirement for constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes throughout the study. The intermittent use of proton pump inhibitor (PPI), H2-antagonists and antacids (including carafate) is only allowed within the following guidelines:
• H2 receptor antagonists until 24 hours (h) of the first dose of study drug
• Antacid formulations until 2 hours before dosing and after 2 hours following dosing.
• PPI is allowed until 5 days before the first study treatment dose. PPIs are prohibited throughout the study
• SAPANISERTIB ARM: Patients receiving systemic corticosteroids (either intravenous \[IV\] or oral steroids, excluding inhalers or low-dose hormone replacement therapy) within 1 week before administration of the first dose of study drug
• History of any of the following within the last 6 months before administration of the first dose of the drug:
• New York Heart Association (NYHA) class III or IV heart failure, ischemic myocardial event, including angina requiring therapy and artery revascularization procedures
• Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures
• Pulmonary embolism
• Any of the following cardiac criteria

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

MLN 8237; osimertinib; sapanisertib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Yasir Y Elamin, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2020
• First Posted: July 21, 2020
• Study Start: June 18, 2020
• Primary Completion: July 27, 2023
• Study Completion: July 27, 2023
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

US (1)