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Testing the Combination of MLN0128 (TAK-228) and AZD9291 in Advanced EGFR (Epidermal Growth Factor Receptor) Mutation Positive Non-small Cell Lung Cancer | Clinical Trials | Clareo Health

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Testing the Combination of MLN0128 (TAK-228) and AZD9291 in Advanced EGFR (Epidermal Growth Factor Receptor) Mutation Positive Non-small Cell Lung Cancer

A Phase 1 Trial of MLN0128 (TAK-228) in Combination With Osimertinib (AZD9291) in Advanced EGFR Mutation Positive Non-Small Cell Lung Cancer (NSCLC) After Progression on a Previous EGFR Tyrosine Kinase Inhibitor

NCT02503722•National Cancer Institute (NCI)

View on ClinicalTrials.gov

Summary

This phase I trial studies the side effects and best dose of sapanisertib when given together with osimertinib in treating patients with stage IV EGFR mutation positive non-small cell lung cancer that has progressed after treatment with an EGFR tyrosine kinase inhibitor. Sapanisertib and osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVES: I. To determine the safety and recommended phase II dose (RP2D) of sapanisertib (MLN0128) (TAK-228) in combination with osimertinib (AZD9291) in patients with advanced epidermal growth factor receptor mutation positive (EGFRm) non-small cell lung cancer (NSCLC) and who are resistant to previous EGFR-tyrosine kinase inhibitor (TKI) therapy. (Dose escalation phase) II. To evaluate the safety and preliminary efficacy of MLN0128 (TAK-228) in combination with osimertinib (AZD9291) in patients with advanced EGFRm NSCLC who are resistant to previous EGFR-TKI therapy with first line osimertinib. (Dose expansion phase) SECONDARY OBJECTIVES: I. To evaluate pharmacokinetic profiles of MLN0128 (TAK-228) in combination with osimertinib (AZD9291). II. To evaluate the response rate, disease control rate and progression free survival of the combination. III. To explore biomarkers of response and resistance to the combination by studying baseline biopsies, resistance biopsies, and serial plasma deoxyribonucleic acid (DNA) specimens. OUTLINE: This is a dose-escalation study of sapanisertib. Patients receive sapanisertib orally (PO) once daily (QD) on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 (day 1 is omitted in cycle 1). Patients also receive osimertinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, and then every 8 weeks thereafter.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Patients with stage IV or recurrent/metastatic histologically or cytologically confirmed non-squamous NSCLC
•NSCLC must harbor an EGFR activating mutation (Exon 21 L858R, Exon 19 deletion)
•Progressive disease on osimertinib (AZD9291) given first line
•For the dose expansion portion ONLY, patient must: 1) have progression of disease with first line osimertinib administered for advanced or metastatic disease as the last previous systemic treatment, 2) be treatment naïve for other 3rd generation EGFR-TKI (CO-1686) and mTOR inhibitors
•Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, defined as at least one lesion that can be accurately measured in at least one dimension \>= 10 mm (\>= 1 cm) by computed tomography (CT) imaging or magnetic resonance imaging (MRI) within 28 days prior to start of protocol therapy; the CT from a combined positron emission tomography (PET)/CT may be used if it is of diagnostic quality; laboratory parameters are not acceptable as the only evidence of disease
•For the dose expansion, no other systemic therapies for advanced/metastatic disease is permissible after first line osimertinib
•Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
•Patients with a prior history of brain metastases are eligible provided:
•* The brain metastases have been treated; patients with small brain metastases for which radiation or surgery is not indicated, may be eligible on discussion with the study chair. Brain metastases that were managed with first line osimertinib is permissible, provided that the brain metastases are stable on a baseline MRI and for whom radiation or surgical resection is not indicated
•* The patient is asymptomatic from the brain metastases
+21 more criteria

Exclusion Criteria

•Any serious intercurrent or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol including but not limited to:
•* Uncontrolled diabetes mellitus (fasting plasma glucose \> 130 mg/dL or 7.2 mmol/L)
•* Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
•* Active infections
•* Gastrointestinal disease limiting the ability to swallow oral medications or absorb oral medications including refractory nausea and vomiting, chronic gastrointestinal diseases, inflammatory bowel disease; malabsorption syndromes
•* Patients with enteric stomata or significant bowel resection
•* Prior history of corneal ulceration
•* Patients with any evidence of severe or uncontrolled systemic liver disease including those with known hepatitis B and hepatitis C (excluding treated hepatitis C that has been cured)
•* Active bleeding diatheses
•Significant active cardiovascular or pulmonary disease including:
+32 more criteria

Locations (5)

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, United States

Yale University

New Haven, Connecticut, United States

Moffitt Cancer Center

Tampa, Florida, United States

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, Canada

University Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

Key Dates

Start Date

March 23, 2017

Primary Completion Date

June 5, 2026

Completion Date

June 5, 2026

Last Updated

March 20, 2026

Enrollment

ESTIMATED participants

Conditions

Metastatic Lung Non-Small Cell CarcinomaRecurrent Lung Non-Small Cell CarcinomaStage III Lung Non-Small Cell Cancer AJCC v7Stage IIIA Lung Non-Small Cell Cancer AJCC v7Stage IIIB Lung Non-Small Cell Cancer AJCC v7Stage IV Lung Non-Small Cell Cancer AJCC v7

Interventions

Laboratory Biomarker Analysis

OTHER

Osimertinib

DRUG

Pharmacological Study

OTHER

Sapanisertib

DRUG

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RECRUITING

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 20, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Testing the Combination of MLN0128 (TAK-228) and AZD9291 in Advanced EGFR (Epidermal Growth Factor Receptor) Mutation Positive Non-small Cell Lung Cancer

Inclusion Criteria

Exclusion Criteria

Testing Osimertinib as a Treatment for Lung Cancers With an EGFR Exon 20 Change

Immune Checkpoint Inhibitor Response in Solid Tumors Using a Live Tumor Diagnostic Platform

Adaptive Radiation Planning for the Reduction of Radiation-Induced Toxicity in Patients With Stage II-IV Non-small Cell Lung Cancer

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PET/CT Changes During Chemoimmunotherapy and Radiation Therapy in Patients With Stage IV Non-small Cell Lung Cancer

Osimertinib and Tegavivint as First-Line Therapy for the Treatment of Metastatic EGFR-Mutant Non-small Cell Lung Cancer