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

Running, not enrolling · Phase 1

Conditions studied: Metastatic Lung Non-Small Cell Carcinoma, Recurrent Lung Non-Small Cell Carcinoma, Stage III Lung Non-Small Cell Cancer AJCC v7, Stage IIIA Lung Non-Small Cell Cancer AJCC v7, Stage IIIB Lung Non-Small Cell Cancer AJCC v7, Stage IV Lung Non-Small Cell Cancer AJCC v7

In brief

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.

Key facts

Study ID

NCT02503722

Run by

National Cancer Institute (NCI)

People needed

36

Starts

2017-03-23

Expected to finish

2027-02-28

Last updated by the study team

2026-06-11

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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
• Corticosteroids and anti-epileptic drugs prescribed for the management of brain metastases have been discontinued at least 7 days prior to registration
• The brain metastases are stable on pre-registration imaging
• Absolute neutrophil count (ANC) >= 1.5 x 10\^9/L
• Hemoglobin >= 90 g/L (or >= 9 g/dL)
• Platelets >= 100 x 10\^9/L
• Calculated creatinine clearance of > 50 mL/min using Cockcroft Gault equation or 24-hour urine sampling
• Total bilirubin =< 1.5 institutional upper limit of normal
• Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
• Fasting plasma glucose =< 130 mg/dL (or 7.2 mmol/L)
• Glycosylated hemoglobin (Hb A1c) =< 7.0%
• Fasting triglycerides =< 300 mg/dL (3.42 mmol/L)
• Cholesterol =< 300 mg/dL (7.75 mmol/L)
• Fridericia's correction formula (QTcF) =< 470 msec
• Patients must have had sufficient time between a prior therapy and resolution of toxicities from the prior therapies prior to registration as follows:
• Prior EGFR inhibitor: A minimum of 7 days must have elapsed from the last dose of the prior EGFR inhibitor and resolution of any drug-related toxicity to =< grade 1 except for alopecia

You may not qualify if…

• 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:
• Uncontrolled hypertension (i.e., systolic blood pressure > 180 mmHg, diastolic blood pressure > 95 mmHg); use of anti-hypertensive agents to control hypertension before cycle 1 day 1 is allowed
• Pulmonary hypertension
• Uncontrolled asthma or oxygen (O2) saturation < 90% by arterial blood gas analysis or pulse oximetry on room air
• Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement
• Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) e.g. medically significant (symptomatic) bradycardia, complete left bundle branch block, third degree heart block and second-degree heart block or history of arrhythmia requiring an implantable cardiac defibrillator; or within the last 6 months before administration of the first dose of drug:
• Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)
• Placement of a pacemaker for control of rhythm
• Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures
• Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures
• New York Heart Association (NYHA) class III or IV heart failure
• Symptomatic pulmonary embolism or asymptomatic pulmonary emboli within the last 3 months
• Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTcF >= 470 msec (mean value) obtained from 3 ECGs, using the screening clinic ECG machine derived QTc value, or history of congenital long QT syndrome, or torsades de pointes); any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval
• Left ventricular ejection fraction (LVEF) by either multigated acquisition (MUGA) or echocardiography (ECHO) less than lower limit of normal
• Patients with active malignancies other than NSCLC or prior curatively treated malignancy at high risk of relapse during the study period with the exception of localized squamous or basal cell skin cancers
• Concurrent anti-cancer therapy

Where it is running

• 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

Full record on ClinicalTrials.gov

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