This phase II trial studies how well osimertinib works in treating patients with non-small cell lung cancer with EGFR exon 20 insertion mutation that is stage IIIB-IV or has come back (recurrent). Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.



Eligible Ages
Over 18 Years
Eligible Genders
Accepts Healthy Volunteers


Inclusion Criteria:

- Participants must have a pathologically-confirmed diagnosis of non-small cell lung
cancer (NSCLC)

- Participants must have advanced disease - either stage IV disease, stage IIIB
disease not amenable to definitive multi-modality therapy, or recurrent disease
after a prior diagnosis of stage I-III disease; all staging is via the American
Joint Committee on Cancer (AJCC)/International Association for the Study of Lung
Cancer (IASLC) 7th edition staging criteria

- An EGFR exon 20 insertion mutation must be detected in the tumor tissue; patients
may be enrolled in the study based on an exon 20 insertion EGFR mutation detected by
any Clinical Laboratory Improvement Act (CLIA)-certified tissue assay

- NOTE: Testing results are to be submitted via Medidata Rave and the study chair
or delegate will review the reports

- Patients must have measurable disease; baseline measurements and ALL sites of
disease must be obtained within 4 weeks to registration

- Patients must have previously received at least one line of therapy for their
advanced lung cancer; there are no restrictions on the maximum number of prior
therapies allowed

- Participants must not have previously received osimertinib

- Participants must have not previously received therapies targeting PDL1, PD1 or
CTLA4 within 6 months (180 days) prior to registration

- Age >= 18 years

- Eastern Cooperative Oncology Group (ECOG) performance status =< 1

- Hemoglobin >= 9.0 g/L (within 4 weeks before registration)

- Leukocytes/white blood cells >= 3,000/mcL (within 4 weeks before registration)

- Absolute neutrophil count >= 1,500/mcL (within 4 weeks before registration)

- Platelets >= 100,000/mcL (within 4 weeks before registration)

- Total bilirubin =< 1.5 x upper limit of normal (ULN) if no liver metastases or =< 3
times ULN in the presence of documented Gilbert's syndrome (unconjugated
hyperbilirubinemia) or liver metastases (within 4 weeks before registration)

- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase
[SGPT]) =< 3 x institutional upper limit of normal; for patients with known hepatic
metastases AST and/or ALT =< 5 x ULN (within 4 weeks before registration)

- Creatinine =< 1.5 x institutional upper limit of normal (within 4 weeks before

- Participants may not have clinically active or symptomatic interstitial lung disease
or interstitial pneumonitis (i.e., affecting activities of daily living or requiring
therapeutic intervention), or a history of clinically significant interstitial lung
disease or radiation pneumonitis

- Participants may not have had radiation to the lung fields within four weeks (28
days) of starting treatment; for patients receiving palliative radiation to thoracic
vertebrae, ribs or other sites where the radiation field includes the lungs,
radiation must be completed at least two weeks before starting treatment; for all
palliative radiation to all other sites, at least 7 days must have elapsed prior to
starting to treatment; at least six months (180 days) must have elapsed from
radiation given with curative intent; palliative radiotherapy to control symptoms
(including gamma knife technique) is permitted; for stereotactic radiosurgery (SRS)
to CNS lesions, osimertinib can be held on the day of radiation only; for palliative
RT to other sites of disease outside of the thorax, osi should be held for a minimum
of 3 days before radiation and 3 days after RT is completed, but the duration of
washout can be adjusted at the investigator's discretion with the approval of the
study principal investigator (PI); for thoracic radiation, a 7-10 day washout period
before the procedure and one week period after procedure before restarting
osimertinib is advised to minimize the risk of pneumonitis; all radiotherapy related
toxicities should be managed and ideally resolved before restarting osimertinib.
Investigators should consider the radiotherapy when assessing causality if there are
any localized AEs following the procedure

- Participants may not have clinically symptomatic brain metastases, leptomeningeal
disease, or spinal cord compression; patients may be on a stable dose of
corticosteroids to control brain metastases if they have been on a stable dose for
two weeks (14 days) prior to study treatment and are clinically asymptomatic

- Patients must have an echocardiogram (ECHO) or a nuclear study (multi-gated
acquisition scan [MUGA] or first pass) within 4 weeks (28 days) prior to
registration to treatment and must not have a left ventricular ejection fraction
(LVEF) < institutional lower limit of normal (LLN); if the LLN is not defined at a
site, the LVEF must be >= 50% for the patient to be eligible

- Participants may not have any of the following cardiac criteria:

- Mean resting corrected QT interval (QTc) >= 470 msec obtained from 3
electrocardiograms (ECGs) using the screening clinic ECG machine-derived QTc

- No history of QT prolongation associated with other medications that required
discontinuation of that medication

- Patient must not be receiving any concomitant medications that are known to be
associated with Torsades de Pointes

- Any clinically important abnormalities in rhythm, conduction or morphology of
resting ECG e.g., complete left bundle branch block, third degree heart block,
second degree heart block, any factors that increase the risk of QTc
prolongation or risk of arrhythmic events such as heart failure, electrolyte
abnormalities (including: serum/plasma potassium < lower limit of normal [LLN];
serum/plasma magnesium < LLN; serum/plasma calcium < LLN), 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

- Symptomatic heart failure - New York Heart Association (NYHA) grade II-IV

- Participants may not have a second, clinically active, cancer; patients with second
cancers which have been treated with curative intent and/or are currently inactive
are allowed

- Participants may not be receiving any other investigational agents; patients
previously treated with investigational agents must complete a washout period of at
least two weeks or five half-lives, whichever is longer, before starting treatment

- Participants may not have uncontrolled intercurrent illness including, but not
limited to, ongoing or active infection, symptomatic congestive heart failure,
unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
situations that would limit compliance with study requirements

- Patients must have no history of hypersensitivity active or inactive excipients of
osimertinib (AZD9291) or drugs with a similar chemical structure or class to
osimertinib (AZD9291)

- Patients must not currently be 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 week prior); all patients must try to avoid
concomitant use of any medications, herbal supplements and/or ingestion of foods
with known inducer effects on CYP3A4

- If medically feasible, patients taking regular medication, with the exception of
potent inducers of CYP3A4, should be maintained on it throughout the study period;
patients taking concomitant medications whose disposition is dependent upon breast
cancer resistance protein (BCRP) or P-glycoprotein (Pgp) and which have a narrow
therapeutic index should be closely monitored for signs of changed tolerability as a
result of increased exposure of the concomitant medication whilst receiving
osimertinib (AZD9291) NOTE: Use of St John's wort is a contra-indication for
osimertinib (AZD9291) use

- If applicable, it is recommended that the starting and maintenance dose of
rosuvastatin (due to BCRP inhibition by AZD9291 [osimertinib]) should be as low as
possible and should be guided by the statin label; monitoring of low-density
lipoprotein (LDL) cholesterol levels is advised; if the subject experiences any
potentially relevant adverse events suggestive of muscle toxicity including
unexplained muscle pain, tenderness, or weakness, particularly if accompanied by
malaise or fever, the statin should be stopped, creatine kinase (CK) levels should
be checked, and any appropriate further management should be taken

- Subjects taking warfarin should be monitored regularly for changes in prothrombin
time or international normalized ratio (INR)

- No unresolved toxicities from prior therapy greater than Common Terminology Criteria
for Adverse Events (CTCAE) grade 1 at the time of starting study treatment, with the
exception of alopecia and grade 2, prior platinum-therapy-related neuropathy

- Patients with refractory nausea and vomiting, chronic gastrointestinal diseases,
inability to swallow the formulated product or previous significant bowel resection
that would preclude adequate absorption of AZD9291 (osimertinib) are ineligible

- Women must not be pregnant or breast-feeding because osimertinib (AZD9291) has been
shown to cause fetal harm in animal models; all females of childbearing potential
must have a blood test or urine study within 2 weeks prior to registration to rule
out pregnancy; a female of childbearing potential is any woman, regardless of sexual
orientation or whether they have undergone tubal ligation, who meets the following
criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has
not been naturally postmenopausal for at least 24 consecutive months (i.e., has had
menses at any time in the preceding 24 consecutive months)

- Women of childbearing potential (WOCBP) and sexually active males must use an
accepted and effective method of contraception while receiving protocol treatment or
abstain from sexual intercourse for the duration of their participation in the
study; WOCBP must use birth control for two weeks prior to the start of the
treatment and continue for 6 weeks after the last dose of the study drug; sexually
active male patients must use effective contraception from day 1 of treatment and
continue for 4 months after the last dose of the study drug

- Other anticancer agents and investigational agents should not be given while the
subject is on study treatment

- Supportive care and other medications that are considered necessary for the
subject's wellbeing may be given at the discretion of the investigator

- A guidance regarding potential interactions with concomitant medications is provided

Study Design

Phase 2
Study Type
Intervention Model
Single Group Assignment
Primary Purpose
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Treatment (osimertinib)
Patients receive osimertinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo MRI or CT with contrast and collection of blood samples throughout the trial.
  • Procedure: Biospecimen Collection
    Undergo collection of blood samples
    Other names:
    • Biological Sample Collection
    • Biospecimen Collected
    • Specimen Collection
  • Procedure: Computed Tomography with Contrast
    Undergo CT with contrast
    Other names:
    • Contrast Enhanced Computed Tomography
    • Contrast-enhanced Computed Tomography
    • CT Scan With Contrast
    • CT with Contrast
  • Procedure: Magnetic Resonance Imaging
    Undergo MRI
    Other names:
    • Magnetic Resonance
    • Magnetic Resonance Imaging (MRI)
    • Magnetic resonance imaging (procedure)
    • Magnetic Resonance Imaging Scan
    • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
    • MR
    • MR Imaging
    • MRI
    • MRI Scan
    • MRIs
    • NMR Imaging
    • NMRI
    • Nuclear Magnetic Resonance Imaging
    • sMRI
    • Structural MRI
  • Drug: Osimertinib
    Given PO
    Other names:
    • AZD 9291
    • AZD-9291
    • AZD9291
    • Mereletinib

Recruiting Locations

MetroHealth Medical Center
Cleveland, Ohio 44109
Site Public Contact

More Details

National Cancer Institute (NCI)

Study Contact

Detailed Description

PRIMARY OBJECTIVE: I. To evaluate the best objective response rate of osimertinib (AZD9291) among patients with EGFR exon 20 insertions. SECONDARY OBJECTIVES: I. To determine the safety profile of 160 mg once daily (QD) dose of osimertinib (AZD9291) in patients with EGFR Exon 20 insertion mutations. II. To determine the progression-free survival. III. To determine the overall survival. TERTIARY OBJECTIVES: I. To characterize molecular markers of response to treatment in circulating tumor deoxyribonucleic acid (DNA). II. To evaluate biomarkers of response to treatment through retrospective analyses of pre-treatment tumor tissue. III. To identify resistance mechanisms to osimertinib (AZD9291) through post-progression tumor biopsies and circulating tumor (ct)DNA. OUTLINE: Patients receive osimertinib orally (PO) once daily (QD) on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo magnetic resonance imaging (MRI) or computed tomography (CT) with contrast and collection of blood samples throughout the trial. After completion of study treatment, patients are followed up at 30 days and every 3 months for up to 5 years.


Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.