Male or female individuals, aged 18 years or older who have Stage IIIB/IV or recurrent NSCLC. Subjects must have tumors that are positive for EGFR-activating mutation, namely, exon 19 deletions, exon 21 L858R mutations, or point mutations at position 719. Enrolled subjects must have a life expectancy of at least 12 weeks and have adequate liver, kidney, and bone marrow function. MedDRA version: 18.0 Level: PT Classification code 10029522
Conditions
Interventions
Product Code: INCB039110
Pharmaceutical Form: Prolonged-release tablet
Current Sponsor code: INCB039110
Other descriptive name: INCB039110
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men or women aged 18 years or older. 2. Histologically or cytologically confirmed diagnosis of nonsquamous NSCLC that is Stage IIIB, Stage IV, or recurrent (including prior Stage II). 3. Documented evidence of an activating mutation in EGFR in tumor samples (exon 19 deletions or point mutation L858R in exon 21 or point mutations at codon 719). 4. Radiographically measurable or evaluable disease. 5. Life expectancy of at least 12 weeks. 6. ECOG performance status of 0 to 2. 7. Negative serum pregnancy test at screening if female of childbearing potential 8. Male subjects must agree to take appropriate precautions to avoid fathering children 9. Ability to swallow and retain orally administered medications. 10. Ability to comprehend and willingness to sign an informed consent form Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 88
Exclusion criteria
Exclusion criteria: 1. Known presence of the T790M mutation in EGFR in tumor samples. 2. Candidates for curative radiation therapy or surgery. 3. Significant GI disorders with diarrhea as a major symptom 4. Distinct or suspected, or history of, pulmonary fibrosis or ILD. 5. Active central nervous system (CNS) metastases that require treatment or history of uncontrolled seizures. 6. Current or previous other malignancy within 2 years of randomization 7. Inadequate renal, hepatic, or bone marrow function demonstrated by Protocol-specified laboratory parameters at the screening visit. 8. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, and arrhythmia-requiring therapy. 9. Significant concurrent, uncontrolled medical condition, including, but not limited to, renal, hepatic, hematological, GI, endocrine, pulmonary, cardiac, neurological, cerebral, or psychiatric disease. 10. Concurrent therapy with a potent CYP3A4 inducer or inhibitor. 11. Chronic or current active infectious disease requiring systemic antibiotics, antifungals, or antivirals. 12. Known human immunodeficiency virus infection, or hepatitis B virus (HBV) or hepatitis C virus (HCV) viremia or at risk for HBV reactivation. 13. Pregnant or breastfeeding women. 14. Unwillingness to be transfused with blood components 15. Active alcohol or drug addiction that would interfere with the subject's ability to comply with the study requirements. 16. Known hypersensitivity to any of the active substances or any of their excipients, including INCB039110 and erlotinib. 17. Prior use of any JAK inhibitor.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1 (Safety Run-in Phase): • To evaluate the safety and tolerability of INCB039110 in combination with erlotinib and select a dose for further evaluation. Phase 2 (Randomized Phase): • To evaluate and compare the OS and PFS of subjects with Stage IIIB/IV or recurrent NSCLC whose tumors have EGFR-activating mutations when treated with INCB039110 in combination with erlotinib versus erlotinib alone. ; Secondary Objective: • To evaluate and compare the efficacy of the 2 treatment groups with respect to overall tumor response and duration of response. • To evaluate and compare the safety and tolerability of INCB039110 in combination with erlotinib versus erlotinib alone. ; Primary end point(s): • Phase 1: Determination of the dose of INCB039110 that is safe and tolerable in combination with erlotinib. • Phase 2 (dual primary endpoints): - Overall survival as determined from the date of randomization until death due to any cause. - Progression-free survival as determined from the randomization date until the earliest date of disease progression, as measured by investigator assessment of objective radiographic disease assessments per RECIST v1.1, or death due to any cause if earlier. ; Timepoint(s) of evaluation of this end point: For the safety run-in phase, the decision to de-escalate the dose will be driven by the number of observed toxicities and can be calculated based on the binomial distribution. The median OS and PFS for the control group are 22.9 months and 10.4 months, respectively; the enrollment and follow-up periods for OS are 15 months and 16 months, respectively, and the follow-up period for PFS is 8 months, after the last subject is randomized | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Analysis of objective response, each subject will be considered a responder if his or her best overall response is PR or better based on RECIST v1.1 criteria. Duration of response defined as the difference of the end of response and the start of response for subjects who have at least 1 response measurement. ; Timepoint(s) of evaluation of this end point: For the analysis of objective response, each subject will be considered a responder if his or her best overall response is PR or better based on RECIST v1.1 criteria. The duration of response is defined as the difference of the end of response and the start of response for subjects who have at least 1 response measurement. The start of a response will be the first visit where the subject achieves PR or better based on RECIST v1.1 criteria. The end of response will be the first visit after PD based on RECIST v1.1 criteria. | — |
Countries
Australia, European Union, Hong Kong, Israel, Korea, Republic of, Russian Federation, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
Incyte Corporation
Outcome results
None listed