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An Open-Label Phase 1/2 Study of Itacitinib in Combination With Osimertinib in Subjects With Non-Small Cell Lung Cancer

NCT02917993

Description:

The purpose of this study is to evaluate the safety and tolerability of itacitinib in combination with osimertinib in subjects with locally advanced or metastatic non-small cell lung cancer (NSCLC).

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

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: An Open-Label Phase 1/2 Study of Itacitinib in Combination With Osimertinib in Subjects With Non-Small Cell Lung Cancer
  • Official Title: An Open-Label Phase 1/2 Study of Itacitinib in Combination With Osimertinib in Subjects With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: INCB 39110-207
  • NCT ID: NCT02917993

Conditions

  • Lung Cancer

Interventions

DrugSynonymsArms
ItacitinibINCB039110Itacitinib + osimertinib
OsimertinibItacitinib + osimertinib

Purpose

The purpose of this study is to evaluate the safety and tolerability of itacitinib in combination with osimertinib in subjects with locally advanced or metastatic non-small cell lung cancer (NSCLC).

Trial Arms

NameTypeDescriptionInterventions
Itacitinib + osimertinibExperimental
  • Itacitinib
  • Osimertinib

Eligibility Criteria

        Inclusion Criteria:

          -  18 years of age or older at screening; outside the U.S. and European Union, an older
             limit could apply depending on local regulation (eg, 19 years and older for South
             Korea and 20 years and older for Taiwan).

          -  Histologically or cytologically confirmed unresectable locally advanced (Stage IIIB)
             or metastatic (Stage IV) NSCLC.

          -  Documented evidence of somatic activating mutation in EGFR (eg, G719X, exon 19
             deletion, L858R, L861Q) in a tumor tissue sample. If a tissue sample is not available,
             then EGFR mutation status may be determined from circulating tumor DNA obtained from a
             blood sample using a validated or approved test kit.

               -  Phase 1: Subjects must have previously received and progressed on or after
                  treatment with an EGFR tyrosine kinase inhibitor (TKI). Additional lines of
                  systemic therapy including investigational agents for locally advanced or
                  metastatic NSCLC are allowed.

               -  Phase 2: Subjects must not have received more than 1 prior line of therapy for
                  locally advanced or metastatic NSCLC. First-line treatment must include an EGFR
                  TKI, and subjects must have documented disease progression during or following
                  treatment. Subjects with disease that progressed more than 6 months after
                  completion of neoadjuvant/adjuvant chemotherapy or chemoradiation therapy are
                  eligible if they received an EGFR TKI as first-line treatment for advanced NSCLC.

                    -  Subjects must have evidence of a T790M mutation in tumor tissue or plasma
                       obtained after disease progression during or after treatment with an EGFR
                       TKI. T790M mutation status from a local laboratory is acceptable; however, a
                       tumor tissue sample or plasma sample suitable for centralized T790M mutation
                       analysis must be available.

          -  Radiographically measurable or evaluable disease per RECIST v1.1.

        Exclusion Criteria:

          -  Known CNS metastases, unless stable and asymptomatic. Subjects with CNS metastases may
             be eligible for the study, provided:

               -  There is no evidence of new or enlarging CNS metastasis or new neurological
                  symptoms attributable to CNS metastases.

               -  Subjects who are receiving corticosteroids must be on a stable or decreasing dose
                  for at least 4 weeks before first dose of study treatment.

          -  Laboratory parameters outside the protocol-defined range.

          -  Clinically significant abnormalities found on an ECG.

          -  Clinically significant or uncontrolled cardiac disease.

          -  Past history of interstitial lung disease (ILD), drug induced ILD, radiation
             pneumonitis that required steroid treatment, or any evidence of clinically active ILD.

          -  Current or previous other malignancy within 2 years of study entry, except cured basal
             or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial
             neoplasm, carcinoma in situ of the cervix, or other noninvasive malignancy.

          -  Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery,
             immunotherapy, biologic therapy, or hormonal therapy).

          -  Any previous use of Janus kinase (JAK) inhibitor, osimertinib, or other EGFR-directed
             therapy for T790M-mt NSCLC.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Frequency, severity, and duration of adverse events (AEs)
Time Frame:From screening through 30-35 days after end of treatment, approximately 2 years.
Safety Issue:
Description:ORR defined as the percentage of subjects who have a confirmed best overall response of complete response (CR) or partial response (PR).

Secondary Outcome Measures

Measure:Phase 1 and Phase 2: Maximum plasma concentration (Cmax) of itacitinib and osimertinib when administered in combination
Time Frame:Measured at protocol-defined study visits from Cycle 1 Day 1 through Cycle 1 Day 28.
Safety Issue:
Description:
Measure:Phase 1 and Phase 2: Area under the plasma concentration-time curve (AUC) of Itacitinib and osimertinib when administered in combination
Time Frame:Measured at protocol-defined study visits from Cycle 1 Day 1 through Cycle 1 Day 28.
Safety Issue:
Description:
Measure:Phase 2: Depth of response (DpR) based on RECIST v1.1
Time Frame:Screening and 8-week intervals throughout the study, approximately 2 years.
Safety Issue:
Description:Defined as the percentage of maximal tumor shrinkage observed at the lowest point (nadir) compared with baseline.
Measure:Phase 2: Progression-free survival (PFS)
Time Frame:Interval from the first day of study treatment until disease progression or death due to any cause, approximately 3 years.
Safety Issue:
Description:
Measure:Phase 2: Overall survival (OS)
Time Frame:Interval from the first day of study treatment until death due to any cause, approximately 3 years.
Safety Issue:
Description:
Measure:Phase 2: Frequency, severity, and duration of AEs
Time Frame:From screening through 30-35 days after end of treatment, approximately 2 years.
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Incyte Corporation

Trial Keywords

  • non-small cell lung cancer
  • locally advanced
  • metastatic
  • epidermal growth factor receptor (EGFR) inhibition
  • Janus kinase inhibition

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