Clinical Trials /

Osimertinib In EGFR Mutant Lung Cancer



This research study is studying a targeted therapy as a possible treatment for Non-Small Cell Lung Cancer (NSCLC) with an EGFR mutation. The names of the study drug involved in this study is: - Osimertinib (Tagrisso)

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:



Phase 2

Trial Eligibility



  • Brief Title: Osimertinib In EGFR Mutant Lung Cancer
  • Official Title: A Phase II Study of Osimertinib With On-study and Post-progression Biopsy in the First Line Treatment of EGFR Inhibitor naïve Advanced EGFR Mutant Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 18-070
  • NCT ID: NCT03586453


  • Carcinoma, Non-Small-Cell Lung


OsimertinibTagrisso, AZD9291Osimertinib


This research study is studying a targeted therapy as a possible treatment for Non-Small Cell Lung Cancer (NSCLC) with an EGFR mutation. The names of the study drug involved in this study is: - Osimertinib (Tagrisso)

Detailed Description

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational drug to learn whether the drug works in treating a
      specific disease. "Investigational" means that the drug is being studied.

      This research study is studying a targeted therapy as a possible treatment for Non-Small Cell
      Lung Cancer (NSCLC) with an EGFR (epidermal growth factor receptor) genetic mutation. The
      EGFR gene produces a protein that helps cells divide. Specific changes or a mutation in the
      genetic information causes abnormal cell division and can lead to lung cancer. Patients who
      have NSCLC with an EGFR gene mutation can be treated by drugs called EGFR tyrosine kinase
      inhibitors (EGFR TKIs). They may stop (or "inhibit") the effect of the mutation in the EGFR

      - Osimertinib has been approved by the FDA (the U.S. Food and Drug Administration) for this

Trial Arms

OsimertinibExperimentalOsimertinib: Oral, once a day, dosage determined per protocol
  • Osimertinib

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have histologically confirmed stage IV NSCLC (per AJCC 7th edition)
             with either the L858R or exon 19 deletion activating EGFR mutation as identified in a
             CLIA-approved laboratory from tumor tissue.

             --Note: recurrent stage IV disease initially diagnosed at an earlier stage is
             considered eligible, provided prior treatment criteria is met.

          -  Participants must have measurable disease at baseline, defined as at least one lesion
             that can be accurately measured in at least one dimension (longest diameter to be
             recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with
             conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical

          -  Participants must be aged ≥ 18 years

          -  Participants must have an ECOG performance status of 0-1 (Appendix A)

          -  Participants must have normal organ and marrow function as defined below:

               -  absolute neutrophil count ≥1,500/mcL

               -  platelets ≥100,000/mcL

               -  hemoglobin >9.0 g/dL

               -  total bilirubin < 1.5 times the ULN if no liver metastases or < 3 times the ULN
                  in the presence of documented Gilbert's syndrome (unconjugated
                  hyperbilirubinemia) or liver metastases

               -  AST(SGOT)/ALT(SGPT) <2.5 × institutional upper limit of normal or <5 times the
                  ULN in the presence of liver metastases

               -  creatinine ≤ 1.5 x institutional upper limit of normal

                  --- OR

               -  creatinine clearance ≥50 mL/min as determined by the Cockcroft-Gault formula.

               -  Note: For participants entering study after starting commercial osimertinib,
                  elevations in hepatic transaminases (AST/ALT) and/or total bilirubin < grade 2 at
                  study entry are acceptable (see protocol Table 2).

          -  Participants must have biopsy tissue at time of diagnosis available and sufficient for
             targeted next-generation sequencing. The sequencing can be performed at a commercial
             vendor such as Foundation Medicine. The testing does not have to be completed prior to
             study enrollment. If the specimen is insufficient a repeat biopsy will need to be

             --Note: Cytology specimen may be acceptable for baseline NGS if tumor cellular content
             is sufficient and following PI approval. If there is no cytology specimen or tissue
             sample available for NGS, plasma-based NGS may be acceptable for enrollment following
             discussion with PI.

          -  For participants entering study after starting commercial osimertinib: a tissue sample
             from the time of diagnosis must be available and sufficient for NGS testing.
             Participants who have had commercial tumor NGS testing performed on their
             pre-osimertinib treated specimen do not need NGS repeated as part of this study.

          -  Participants must be willing to undergo a repeat tumor biopsy during study treatment
             between cycles 4 and 8 (if considered medically safe) and at the time of disease

          -  Participants must be ≥2 weeks since any major surgery (excluding vascular access
             placement, mediastinoscopy, or biopsies performed by an interventional service)

          -  Male patients should be asked to use barrier contraceptives (i.e., by use of condoms)
             during sex with all partners who are women of child bearing potential, including
             pregnant women, during the trial and for a washout period of 4 months. Male patients
             should avoid procreation for 4 months after completion of trial treatment. Patients
             should refrain from donating sperm from the start of dosing until 4 months after
             discontinuing study treatment.

          -  Female patients (women of child-bearing potential): Willing to use adequate
             contraception (barrier or abstinence) at least 2 weeks before receiving any study
             medication, while on treatment with study drug, and for 6 weeks after finishing

          -  Female patients: Must not be pregnant or breast-feeding. Women of child-bearing
             potential must have a negative pregnancy test (urine or serum) prior to start of
             dosing or must have evidence of non-child-bearing potential by fulfilling one of the
             following criteria at screening:

               -  a) Post-menopausal defined as aged more than 50 years and amenorrheic for at
                  least 12 months following cessation of all exogenous hormonal treatments

               -  b) Women under 50 years are considered postmenopausal if they have been
                  amenorrheic for 12 months or more following cessation of exogenous hormonal
                  treatments and with LH and FSH levels in the post-menopausal range for the

               -  c) Documentation of irreversible surgical sterilization by hysterectomy,
                  bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation.

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Subjects may enter the study even if they have started their treatment using
             commercial osimertinib. Subjects may enter the study anytime during the first 3 months
             of receiving commercial osimertinib therapy (up to 84 days of commercial osimertinib
             before entering the study). In order to enter the study after starting commercial
             osimertinib, subjects must meet all eligibility criteria listed above, have baseline
             and follow up imaging available for review for response assessment, and must not have
             developed disease progression during the first 3 months of commercial osimertinib

        Exclusion Criteria:

          -  Subjects should not enter the study if any of the following exclusion criteria are

          -  Prior or ongoing treatment with any of the following:

               -  EGFR targeted therapy (TKI or antibody) or any other targeted therapies targeting
                  the ERBB family except for subjects receiving first line osimertinib during the
                  first three months of therapy.

               -  Any cytotoxic chemotherapy, investigational agents, immunotherapy or anticancer
                  drugs for the treatment of metastatic NSCLC

               -  Note: Patients who have completed adjuvant or neo-adjuvant chemotherapy > 6
                  months ago are considered treatment naïve

          -  Prior radiotherapy, including CNS radiation, within 2 weeks of the first dose of study

          -  Uncontrolled central nervous system (CNS) disease, including parenchymal brain
             metastases, leptomeningeal disease, or spinal cord compression. Patients with
             asymptomatic untreated brain metastases are eligible. Patients with treated CNS
             disease will be allowed to enroll provided they have asymptomatic clinically confirmed
             stable disease with ≥2 weeks since definitive CNS therapy (radiation or surgery) and
             ≥2 weeks without systemic steroids. Patients may undergo either whole brain radiation
             or stereotactic radiosurgery prior to study entry.

          -  History of allergic reactions attributed to compounds, or any of its excipients, of
             similar chemical or biologic composition to osimertinib.

          -  Patients currently receiving and unable to stop using medications or herbal
             supplements known to be potent inhibitors or inducers of CYP3A4. The full list of
             medications that would make a patient ineligible are provided in Appendix B, along
             with indicated washout times.

          -  Any unresolved toxicities from prior therapy, including commercial osimertinib,
             greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the
             time of starting study treatment.

          -  Malignancies within the past 3 years excluding adequately treated basal or squamous
             cell carcinomas of the skin without local or distant metastases.

          -  Refractory nausea and vomiting, chronic gastrointestinal diseases, previous
             significant bowel resection, or any process that compromises the ability to swallow or
             absorb oral medication

          -  Significant medical history or unstable medical comorbidities, including:

               -  heart disease including congestive heart failure (NYHA Grade II or greater);
                  unstable angina; prior myocardial infarction (NSTEMI or 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 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, PR interval >250msec, have normal QT interval on ECG
                  evaluation QT corrected Fridericia (QTcF) of ≤ 450 ms in males or ≤ 470 ms in

               -  any factors that increase the risk of QTc prolongation or risk of arrhythmic
                  events such as heart failure, hypokalemia, 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 the prolong the QT
                  interval and cause Torsades de Pointes and listed in Appendix B that a patient is
                  unable to stop

               -  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 bleeding diatheses, which in the investigator's opinion makes it
                  undesirable for the patient to participate in the trial or which would jeopardize
                  compliance with the protocol

               -  known 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.

               -  cardiac ejection fraction of < 45%

               -  Any evidence of severe or uncontrolled systemic diseases, including active
                  bleeding diatheses, which in the investigator's opinion makes it undesirable for
                  the patient to participate in the trial or which would jeopardize compliance with
                  the protocol

          -  Known to be T790M+ (on pre-treatment tumor or plasma) or known germline T790M. Note:
             testing is not required for study entry.

          -  Males and females of reproductive potential who are not using an effective method of
             birth control and females who are pregnant or breastfeeding or have a positive (urine
             or serum) pregnancy test prior to study entry. Women of child-bearing potential must
             have a negative pregnancy test prior to start of dosing.

          -  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 osimertinib.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Mechanisms of resistance to Osimertinib
Time Frame:4 Months
Safety Issue:
Description:Evaluated by comparing the genomic changes using targeted next generation sequencing in the post-osimertinib tumor to the pre-treatment tumor specimen.

Secondary Outcome Measures

Measure:Best objective response
Time Frame:6 months
Safety Issue:
Description:Best objective response will be evaluated via RECIST 1.1 criteria. RECIST1.1 measurements of CT scans will be measured every 2 cycles on treatment to determine the objective response rate for patients being treated with osimertinib.
Measure:Overall Response Rate
Time Frame:3 years
Safety Issue:
Description:Defined as the proportion of patients with best response of CR or PR per investigator assessment using RECIST 1.1. start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started.
Measure:Progression-free survival (PFS)
Time Frame:2 years
Safety Issue:
Description:Time from registration to documented disease progression or death from any cause, whichever occurs first. The Kaplan-Meier method will be used to determine the progression-free survival of patients enrolled on protocol and treated with combination osimertinib and selumetinib.
Measure:Overall survival
Time Frame:2 years
Safety Issue:
Description:Survival follow-up with clinic visits or phone calls will be used to monitor for overall survival from time of study randomization to death from any cause. The Kaplan-Meier method will be used to calculate overall survival.


Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Non-Small Cell Lung Cancer (NSCLC)
  • Epidermal Growth Factor Receptor (EGFR) mutation

Last Updated

May 6, 2021