Pembrolizumab and Itacitinib (INCB039110) for Non-Small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT03425006
• Recruitment Status: Terminated
• First Posted: February 7, 2018
• Last Update Posted: May 27, 2022
• Sponsor: University of Pennsylvania
• Information provided by (Responsible Party): University of Pennsylvania

Tracking Information

• First Submitted Date: January 22, 2018
• First Posted Date: February 7, 2018
• Last Update Posted Date: May 27, 2022
• Actual Study Start Date: June 18, 2018
• Actual Primary Completion Date: June 17, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 23, 2021)

• 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 ]
  Responses will be compared subject's baseline assessment and historical controls using pembrolizumab monotherapy.
• Evaluate toxicities (CTCAE v5.0 scoring) of pembrolizumab and itacitinib in patients with previously untreated, PD-L1 positive metastatic NSCLC [ Time Frame: 16 weeks ]

Original Primary Outcome Measures (submitted: February 5, 2018)

• 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 ]
  Responses will be compared subject's baseline assessment and historical controls using pembrolizumab monotherapy.
• Evaluate toxicities (CTCAE v4.0 scoring) of pembrolizumab and itacitinib in patients with previously untreated, PD-L1 positive metastatic NSCLC [ Time Frame: 36 Months ]

Current Secondary Outcome Measures (submitted: July 23, 2021)

• Median progression free survival (PFS) for subjects treated with pembrolizumab and itacitinib. [ Time Frame: 12 weeks ]
• Duration of response (DOR) for subjects treated with pembrolizumab and itacitinib. [ Time Frame: 12 weeks ]
• Overall survival (OS) for subjects treated with pembrolizumab and itacitinib. [ Time Frame: 16 weeks ]

Original Secondary Outcome Measures (submitted: February 5, 2018)

• Determine the median progression free survival (PFS) for subjects treated with pembrolizumab and itacitinib. [ Time Frame: 36 Months ]
• Determine the duration of response (DOR) for subjects treated with pembrolizumab and itacitinib. [ Time Frame: 36 Months ]
• Determine overall survival (OS) for subjects treated with pembrolizumab and itacitinib. [ Time Frame: 36 Months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pembrolizumab and Itacitinib (INCB039110) for Non-Small Cell Lung Cancer
• Official Title: Phase II Study of Pembrolizumab and Itacitinib (INCB039110) for First Line Treatment of Metastatic Non-Small Cell Lung Cancer Expressing PD-L1
• Brief Summary: 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non Small Cell Lung Cancer

Intervention

• Drug: Itacitinib
  a JAK 1 selective small molecule inhibitor
  Other Name: INCB039110
• Biological: Pembrolizumab
  a highly selective humanized monoclonal antibody (mAb)

Study Arms

Experimental: Itacitinib and Pembrolizumab

Interventions:

• Drug: Itacitinib
• Biological: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: May 25, 2022): 31
• Original Estimated Enrollment (submitted: February 5, 2018): 48
• Actual Study Completion Date: October 11, 2021
• Actual Primary Completion Date: June 17, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 1. Stage IV or metastatic 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. 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: Absolute neutrophil count (ANC) ≥1,250/mcL; Platelets ≥100,000/mcL; Hemoglobin ≥9 g/dL or ≥5.6 mmol/L; Serum creatinine ≤1.5 X upper limit of normal (ULN) OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥50 mL/min for subject with creatinine levels > 1.5 X institutional ULN; 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 immunodeficiencywithin 7 days prior to eligibility confirmation by the physician-investigator.
• 6. Prior monoclonal antibodies used for the treatment of NSCLC within 4 weeks prior to eligibility confirmation by the physician-investigator, 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. 8. Active autoimmune disease requiring systemic immunosuppressive treatment within the past 3 months prior to eligibility confirmation by the physician-investigator. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03425006
• Other Study ID Numbers: UPCC# 09517; IRB# 828910
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University of Pennsylvania
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Pennsylvania
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Corey Langer, MD; University of Pennsylvania

• PRS Account: University of Pennsylvania
• Verification Date: May 2022