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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Itacitinib
* Drug: Osimertinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Itacitinib + osimertinib<br> | Drug: Itacitinib<br>* In Phase 1, itacitinib at a protocol-defined starting dose, with subsequent dose escalation based on protocol-specific criteria. In Phase 2, itacitinib at the recommended dose from Phase 1.<br>* Other names: INCB039110;Drug: Osimertinib<br>* Osimertinib 80 mg once daily (QD)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Frequency, severity, and duration of adverse events (AEs) |  | From screening through 30-35 days after end of treatment, approximately 2 years. | 
| Phase 1: Number of subjects with dose-limiting toxicities (DLTs) |  | Day 1 through Day 28 | 
| Phase 2: Objective response rate (ORR) based on RECIST v1.1 | ORR defined as the percentage of subjects who have a confirmed best overall response of complete response (CR) or partial response (PR). | Screening and 8-week intervals throughout the study, approximately 2 years. | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-small cell lung cancer, locally advanced, metastatic, epidermal growth factor receptor (EGFR) inhibition, Janus kinase inhibition