Clinical Trials /

Osimertinib for NSCLC With EGFR Exon 20 Insertion Mutation

NCT03414814

Description:

This is a single-arm, non-randomized multicentre phase 2 study in NSCLC patients with EGFR exon 20 insertion mutation, whose disease has progressed on standard chemotherapy.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Osimertinib for NSCLC With EGFR Exon 20 Insertion Mutation
  • Official Title: Phase II Study of Osimertinib in NSCLC Patients With EGFR Exon 20 Insertion Mutation

Clinical Trial IDs

  • ORG STUDY ID: KCSG LU17-19
  • NCT ID: NCT03414814

Conditions

  • Locally Advanced or Metastatic NSCLC

Interventions

DrugSynonymsArms
Osimertinib 80 MG [Tagrisso]Osimertinib

Purpose

This is a single-arm, non-randomized multicentre phase 2 study in NSCLC patients with EGFR exon 20 insertion mutation, whose disease has progressed on standard chemotherapy.

Detailed Description

      EGFR exon 20 insertion-mutant NSCLCs are generally resistant to 1st-generation EGFR tyrosine
      kinase inhibitors (TKIs) as well as 2nd-generation EGFR TKIs (overall response rates of
      0-8.7%). Osimertinib is an oral, potent, irreversible EGFR-TKI selective for sensitizing EGFR
      and EGFR T790M resistance mutations with a significant selectivity margin against wild-type
      EGFR. Osimertinib is potent with a wide therapeutic window in Ba/F3 cells with EGFR exon 20
      insertion mutations. Therefore, this study will be performed to investigate the efficacy of
      osimertinib in NSCLC patients with EGFR exon 20 insertion mutation
    

Trial Arms

NameTypeDescriptionInterventions
OsimertinibExperimentalOsimertinib at 80mg dose will be administered orally once daily.
  • Osimertinib 80 MG [Tagrisso]

Eligibility Criteria

        Inclusion Criteria:

          1. Provision of informed consent prior to any study specific procedures

          2. Male or female must be > 19 years of age.

          3. Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy
             with local confirmation of the presence of the EGFR exon 20 insertion mutation

          4. Disease progression while on standard chemotherapy (platinum doublet chemotherapy or
             single-agent chemotherapy in selected patients)

          5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

          6. Patients must have a life expectancy ≥ 12 weeks

          7. Females should be using adequate contraceptive measures, should not be breast feeding
             and must have a negative pregnancy test prior to start of dosing if of child-bearing
             potential or must have evidence of non-child-bearing potential by fulfilling one of
             the following criteria at screening:

          8. Male patients should be willing to use barrier contraception

          9. Patient is willing and able to comply with the protocol for the duration of the study
             including undergoing treatment and scheduled visits and examinations including follow
             up.

         10. At least one measurable lesion

         11. Provision of archival FFPE tissue

         12. Provision of informed consent for translational genetic research

        Exclusion Criteria:

          1. Involvement in the planning and/or conduct of the study (applies to both sponsor staff
             and/or staff at the study site)

          2. Previous treatment with osimertinib (3rd generation EGFR TKIs such as olumtinib,
             EGF816 etc)

          3. Treatment with an investigational drug within five half-lives of the compound

          4. 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)
             (Appendix A). All patients must try to avoid concomitant use of any medications,
             herbal supplements and/or ingestion of foods with known inducer/inhibitory effects on
             CYP3A4.

          5. Any 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.

          6. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled
             hypertension and active bleeding diatheses, which in the investigator's opinion makes
             it undesirable for the patient to participate in the trial or which would jeopardise
             compliance with the protocol, or active infection including hepatitis B, hepatitis C
             and human immunodeficiency virus (HIV). Screening for chronic conditions is not
             required.

          7. Patients with symptomatic CNS metastases who are neurologically unstable; however,
             those with asymptomatic CNS metastases who do not require steroids for at least 4
             weeks prior to start of osimertinib are eligible.

          8. Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid
             treatment, or any evidence of clinically active ILD

          9. Inadequate bone marrow reserve or organ function

         10. QTc prolongation (mean resting corrected QTc > 470 msec)

         11. 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

         12. History of hypersensitivity to osimertinib (or drugs with a similar chemical structure
             or class to osimertinib) or any excipients of these agents

         13. 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

         14. Judgment by the Investigator that the patient should not participate in the study if
             the patient is unlikely to comply with study procedures, restrictions and requirements

         15. Previous allogeneic bone marrow transplant.

         16. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the
             genetic sample collection.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate
Time Frame:Through study completion, an average of 1 year
Safety Issue:
Description:Investigator-assessed, confirmed objective response by RECIST version 1.1

Secondary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events
Time Frame:Through study completion, an average of 1 year
Safety Issue:
Description:AEs/SAEs as defined by NCI CTCAE version 4.0
Measure:Progression-free survival
Time Frame:From date of initiation until the date of first documented progression, whichever came first, assessed up to 2 years
Safety Issue:
Description:PFS as defined by RECIST version 1.1
Measure:Overall survival
Time Frame:Through study completion, an average of 2 years
Safety Issue:
Description:OS as defined by RECIST version 1.1
Measure:Duration of response
Time Frame:Through study completion, an average of 1 year
Safety Issue:
Description:Duration of response as defined by RECIST version 1.1

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Seoul National University Hospital

Trial Keywords

  • NSCLC
  • Osimertinib
  • EGFR exon 20 insertion mutation

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