Study to Assess the Effect of AZD9291 on the Blood Levels of Simvastatin in Patients With EGFRm+ NSCLC

Completed · Phase 1

Conditions studied: Non Small Cell Lung Cancer

In brief

This is a Phase I, open-label, 2-part study in patients with a confirmed diagnosis of epidermal growth factor receptor (EGFR) mutation positive (EGFRm+) non-small cell lung cancer (NSCLC), who have progressed following prior therapy with an approved EGFR tyrosine kinase inhibitor (TKI) agent. Part A will assess the effect of AZD9291 on the pharmacokinetic (PK) parameters of simvastatin and simvastatin acid, following multiple oral dosing of AZD9291 in a fasted state. Part B will allow patients further access to AZD9291 after the PK phase (Part A) and will provide for additional safety data collection. All patients from Part A who completed treatment may continue to receive AZD9291 80 mg once daily until: disease progression; they are no longer deriving clinical benefit; or any other reason.

Key facts

Study ID

NCT02197234

Run by

AstraZeneca

People needed

52

Starts

2014-12-22

Expected to finish

2024-06-03

Last updated by the study team

2025-11-20

Who can join

Age: 18 and older, up to 130. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Participation in another study with an IP during the last 14 days (or a longer period depending on the defined characteristics of the agents used).
• Treatment with any of the following: Treatment with an EGFR TKI (eg, erlotinib or gefitinib) within 8 days or approx. 5 x half-life, whichever is the longer, of the first dose of study treatment; any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of the first dose; major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment; radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment, with the exception of patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation which must be completed within 4 weeks of the first dose; patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inhibitors of CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3 week prior). All patients must avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer/inhibitory effects on CYP3A4.
• Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy.
• Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first administration of the IP until the final PK sample collection on Day 32 of Part A.
• Spinal cord compression or brain metastases unless asymptomatic, stable and not requiring steroids for at least 4 weeks prior to start of study treatment.
• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the PI's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C, and HIV. Screening for chronic conditions not required.
• Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: ANC <1.5 x 10\^9/L; platelet count <100 x 10\^9/L; haemoglobin <90 g/L; ALT >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases; Aspartate aminotransferase (AST) >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases; total bilirubin >1.5 times ULN if no liver metastases or >3 times ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases; creatinine >1.5 times ULN concurrent with creatinine clearance <50 ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN.
• Any of the following cardiac criteria: mean resting corrected QT interval corrected for heart rate using Fridericia's correction factor (QTcF) >470 msec obtained from 3 ECGs; any clinically important abnormalities in rhythm, conduction or morphology of resting ECG eg, complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250 msec; 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 age of 40 or any concomitant medication known to prolong the QT interval.
• Patients unable to swallow oral medication or patients with GI disorders or significant GI resection likely to interfere with the absorption of AZD9291.
• Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
• Women who are breastfeeding.
• Patients with a known hypersensitivity to AZD9291, simvastatin, or any of the excipients of the products.
• Concomitant medication contraindicated for use with simvastatin due to drug interaction associated with increased risk of rhabdomyolysis (including, but not limited to): itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors (eg, nelfinavir), nefazodone, cyclosporine, danazol, gemfibrozil, amiodarone, amlodipine.
• 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA)-reductase inhibitors, such as lovastatin and simvastatin.
• For optional genetic research: Previous allogenic bone marrow transplant or non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.

Where it is running

• Research Site — Atlanta, Georgia, United States
• Research Site — Leuven, Belgium
• Research Site — Angers, France
• Research Site — Dijon, France
• Research Site — Marseille, France
• Research Site — Rennes, France
• Research Site — Saint-Herblain, France
• Research Site — Seongnam-si, South Korea
• Research Site — Seoul, South Korea
• Research Site — Seoul, South Korea
• Research Site — Seoul, South Korea
• Research Site — Seoul, South Korea
• Research Site — Badalona, Spain
• Research Site — Barcelona, Spain
• Research Site — Madrid, Spain
• Research Site — Seville, Spain

Full record on ClinicalTrials.gov

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