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Osimertinib in Treating Participants with Stage IV Non-Small Cell Lung Cancer with Uncommon EGFR Mutations

Trial Status: Active

This phase II trial studies how well osimertinib works in treating participants with stage IV non-small cell lung cancer with EGFR mutations. Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Inclusion Criteria

  • EGFR mutations as performed on a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory demonstrating EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q. Patients with compound (also referred to as multiple mutations) will be eligible provided the non-small cell lung cancer [NSCLC] demonstrates one of these mutations)
  • Histological or cytological confirmation diagnosis of stage 4 NSCLC per American Joint Committee on Cancer (AJCC) version (v) 7
  • Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Absolute neutrophil count (ANC) >= 1,500 / ml obtained =< 14 days prior to study initiation
  • Platelet count >= 100,000 / ml obtained =< 14 days prior to study initiation
  • Hemoglobin >= 9.0 g / dl obtained =< 14 days prior to study initiation
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5 times upper limit of normal (ULN) if no demonstrable liver metastases or < 5 times ULN in the presence of liver metastases obtained =< 14 days prior to study initiation
  • 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 obtained =< 14 days prior to study initiation
  • Cockcroft-Gault calculated creatinine clearance of >= 45 ml/min or creatinine =< 1.5 x ULN obtained =< 14 days prior to study initiation
  • Have normal QT interval on electrocardiogram (ECG) evaluation QT corrected of =< 450 ms in males or =< 470 ms in females obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine-derived corrected QT (QTc) value
  • Cardiac ejection fraction of >= 45%
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Negative pregnancy test done =< 7 days (or per institutional policy) prior to treatment, for women of childbearing potential only. Female must use highly effective contraceptive measures, and must have a negative pregnancy test or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: * Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments * Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the institution * Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
  • Male subjects must be willing to use barrier contraception
  • Provision of written informed consent prior to any study-specific procedures

Exclusion Criteria

  • Prior therapy with EGFR tyrosine kinase inhibitor (TKI) therapy
  • Greater than 2 lines of prior systemic therapy for metastatic non-small cell lung cancer
  • Any cytotoxic chemotherapy or other anticancer drugs from previous treatment regimen or clinical study within 14 days of first dose of study drug
  • Treatment with an investigational drug within 5 half-lives of the compound
  • Other active malignancy =< 2 years prior to study enrollment. EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix. NOTE: If there is a history of prior malignancy, patients must not be receiving other specific treatment (i.e. hormonal therapy) for their cancer
  • Prior radiotherapy =< 14 days
  • Untreated symptomatic brain metastases (treated brain metastases are allowed provided > 14 days have elapsed from completion of radiotherapy and patient is neurologically stable as assessed by treating physician)
  • Malabsorption syndrome, refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib
  • Detection of concurrent EGFR mutation with exon 20 T790M, exon 19 deletion, exon 21 L858R mutation or exon 20 insertion. Patients with compound (also referred to as multiple mutations) will be excluded if the molecular testing includes one of these mutations
  • Active pregnancy or breast-feeding: pregnant women are excluded from this study because the effects of osimertinib on the development of the fetus are unknown, and there is potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with osimertinib, breastfeeding should be discontinued if the mother is treated with these agents
  • Grade >= 2 blurred vision, conjunctivitis, corneal ulcer, dry eye, or keratitis
  • Men who intend to father children during the study or within 4 months afterward are excluded
  • Major surgery within 4 weeks of first dose of study drug
  • Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment, with the exception of alopecia or neuropathy
  • Currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 weeks prior)
  • Significant medical history or unstable medical comorbidities, including but not limited to: * Heart disease including congestive heart failure (New York Heart Association [NYHA] grade II or greater); unstable angina; prior myocardial infarction (non-ST-elevation myocardial infarction [NSTEMI] or ST-elevation myocardial infarction [STEMI]) within 6 months prior to study enrollment; hypertension with a systolic blood pressure of > 150 mm Hg or diastolic blood pressure of > 100 mm Hg while on antihypertensive medication * Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as 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 * 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 * Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses * Active infection or ongoing antiviral medication for viral infections including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). Screening for chronic conditions is not required. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with osimertinib * Ongoing use of warfarin (injectable low-molecular weight heparins are permitted). Patients must be off warfarin for > 7 days prior to enrollment

North Carolina

Duke University Medical Center
Status: ACTIVE
Contact: Thomas E. Stinchcombe
Phone: 919-681-9509


Ohio State University Comprehensive Cancer Center
Status: ACTIVE
Contact: Gregory A. Otterson
Phone: 614-293-2887


University of Pittsburgh Cancer Institute (UPCI)
Status: ACTIVE
Contact: Liza C. Villaruz
Phone: 412-692-4724


I. Objective response rate.


I. Progression free survival.

II. Safety.

III. Overall survival.


I. Objective response rate (ORR) and progression free survival (PFS) in the specific mutation subsets of exon 18 G719X, exon 20 S7681, exon 21 L861Q or compound mutations.


Participants receive osimertinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up every 6-12 weeks and then every 3 months for up to 2 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Duke University Medical Center

Principal Investigator
Thomas E. Stinchcombe

  • Primary ID Pro00088376
  • Secondary IDs NCI-2018-00883
  • ID NCT03434418