Clinical Trials /

Pembrolizumab and Itacitinib (INCB039110) for NSCLC

NCT03425006

Description:

This is a single center, single arm phase 2 study to establish the safety and efficacy of itacitinib (also known as INCB039110) administered in combination with pembrolizumab in patients with metastatic PD-L1 positive non-small cell lung cancer (NSCLC).

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab and Itacitinib (INCB039110) for NSCLC
  • Official Title: Phase II Study of Pembrolizumab and Itacitinib (INCB039110) for First Line Treatment of Metastatic Non-Small Cell Lung Cancer Expressing PD-L1

Clinical Trial IDs

  • ORG STUDY ID: UPCC# 09517; IRB# 828910
  • NCT ID: NCT03425006

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
ItacitinibINCB039110Itacitinib and Pembrolizumab
PembrolizumabItacitinib and Pembrolizumab

Purpose

This is a single center, single arm phase 2 study to establish the safety and efficacy of itacitinib (also known as INCB039110) administered in combination with pembrolizumab in patients with metastatic PD-L1 positive non-small cell lung cancer (NSCLC).

Trial Arms

NameTypeDescriptionInterventions
Itacitinib and PembrolizumabExperimental
  • Itacitinib

Eligibility Criteria

        Inclusion Criteria:

          -  1. Stage IV non-small cell lung cancer (NSCLC)

          -  2. Provide written informed consent for the trial.

          -  3. Patients ≥ 18 years of age

          -  4. Tumor PD-L1≥ 50% as assessed by the PD-L1 IHC 22C3 pharmDx assay (Dako North
             America).

          -  5. Subject must have adequate tumor burden at a safely accessible site for biopsy by
             either bronchoscopy or imaging guidance. NOTE: If sites chosen for biopsy were
             previously irradiated, there must be evidence of tumor growth/viable tumor as assessed
             by the investigator.

          -  6. At least one measurable lesion according to Response Evaluation Criteria in Solid
             Tumors (RECIST) v1.1

          -  7. ECOG performance status 0 or 1

          -  8. Adequate Organ Function Laboratory Values System Laboratory Value Hematological
             Absolute neutrophil count (ANC) ≥1,250/mcL Platelets ≥100,000/mcL Hemoglobin ≥9 g/dL
             or ≥5.6 mmol/L Renal Serum creatinine OR ≤1.5 X upper limit of normal (ULN) OR
             Measured or calculated creatinine clearance (GFR can also be used ≥50 mL/min for
             subject with creatinine levels in place of creatinine or CrCl) > 1.5 X institutional
             ULN Creatinine clearance should be calculated per institutional standard. Hepatic
             Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total
             bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for
             subjects with liver metastases

          -  9. Subjects of reproductive potential must agree to use acceptable birth control
             methods.

        Exclusion Criteria:

          -  1. Sensitizing mutations in Epidermal growth factor receptor (EGFR) or anaplastic
             lymphoma kinase (ALK) or ROS1 proto-oncogene receptor tyrosine kinase (ROS1)
             translocations

          -  2. Currently participating in or has participated in a study of an investigational
             agent or anticipated use of an investigational device within 4 weeks of the first dose
             of study treatment.

          -  3. Untreated symptomatic central nervous system (CNS) metastases and/or carcinomatous
             meningitis.

          -  4. Received prior systemic cytotoxic chemotherapy, biologic therapy, targeted therapy
             or immunotherapy for incurable (metastatic) NSCLC.

          -  5. Diagnosis of immunodeficiency or exposure to systemic corticosteroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to enrollment. (Nasal or
             oral inhalers are permissible). Patients on physiologic replacement doses of steroids
             (mineralocorticoid or less than or equal to a prednisone 10 mg daily dose) will also
             be permitted to enroll.

          -  6. Prior monoclonal antibody within 4 weeks prior to enrollment, or individuals who
             have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents
             administered more than 4 weeks earlier.

          -  7. Known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin, non-invasive bladder tumors, or in situ cervical cancer

          -  8. Active autoimmune disease requiring systemic treatment within the past 3 months
             prior to enrollment. Subjects that require intermittent use of steroid-containing
             bronchodilators or local steroid injections or topical steroid medications are not
             excluded from the study. Subjects with hypothyroidism stable on hormone replacement or
             Sjogren's syndrome are not excluded from the study.

          -  9. Interstitial lung disease or history of pneumonitis that has required oral or IV
             steroids

          -  10. Active infection requiring systemic therapy with IV antibiotics

          -  11. History or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

          -  12. Known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  13. Pregnant or breastfeeding women

          -  14. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
             anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4).

          -  15. Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

          -  16. Known active Hepatitis B (e.g., HBsAg positive or HBV DNA detectable) or Hepatitis
             C (e.g., HCV RNA [qualitative] is detected).

          -  17. Anticipated receipt of any live vaccine within 30 days prior to the first dose of
             trial treatment.

        Note: For the purposes of determining eligibility above, enrollment is defined as the date
        of subject consent.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response Rate at 12 weeks according to RECIST 1.1 for the combination of pembrolizumab and itacitinib among patients with previously untreated, PD-L1 positive metastatic NSCLC.
Time Frame:12 weeks
Safety Issue:
Description:Responses will be compared subject's baseline assessment and historical controls using pembrolizumab monotherapy.

Secondary Outcome Measures

Measure:Median progression free survival (PFS) for subjects treated with pembrolizumab and itacitinib.
Time Frame:36 Months
Safety Issue:
Description:
Measure:Duration of response (DOR) for subjects treated with pembrolizumab and itacitinib.
Time Frame:36 Months
Safety Issue:
Description:
Measure:Overall survival (OS) for subjects treated with pembrolizumab and itacitinib.
Time Frame:36 Months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Pennsylvania

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