An Open-Label Phase 1/2 Study of Itacitinib in Combination With Osimertinib in Subjects With Non-Small Cell Lung Cancer
- Registration Number
- NCT02917993
- Lead Sponsor
- Incyte Corporation
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 59
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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).
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Histologically or cytologically confirmed unresectable locally advanced (Stage IIIB) or metastatic (Stage IV) NSCLC.
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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.
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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.
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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.
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Radiographically measurable or evaluable disease per RECIST v1.1.
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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.
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Laboratory parameters outside the protocol-defined range.
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Clinically significant abnormalities found on an ECG.
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Clinically significant or uncontrolled cardiac disease.
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Past history of interstitial lung disease (ILD), drug induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD.
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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.
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Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or hormonal therapy).
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Any previous use of Janus kinase (JAK) inhibitor, osimertinib, or other EGFR-directed therapy for T790M-mt NSCLC.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Itacitinib + osimertinib Itacitinib - Itacitinib + osimertinib Osimertinib -
- Primary Outcome Measures
Name Time Method 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 Screening and 8-week intervals throughout the study, approximately 2 years. 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
Name Time Method 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 Screening and 8-week intervals throughout the study, approximately 2 years. Defined as the percentage of maximal tumor shrinkage observed at the lowest point (nadir) compared with baseline.
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.
Trial Locations
- Locations (31)
Valley Hospital, 223 N Van Dien Avenue
πΊπΈRidgewood, New Jersey, United States
West Virginia University Cancer Institute, 1 Medical Center Drive
πΊπΈMorgantown, West Virginia, United States
University of Texas -MD Anderson Cancer Center, 1515 Holcombe Blvd.
πΊπΈHouston, Texas, United States
Texas Oncology - San Antonio Medical, 5206 Research Drive
πΊπΈSan Antonio, Texas, United States
National Taiwan University Hospital, 7 Zhongshan South Road
π¨π³Taipei, Zhongzheng District, Taiwan
University California San Francisco Thoracic Surgery and Oncology Clinic, 1600 Divisadero Street, Floor 4
πΊπΈSan Francisco, California, United States
Henry Ford Health System, 2799 W Grand Blvd.
πΊπΈDetroit, Michigan, United States
Rocky Mountain Cancer Center, 1800 Williams Street, Suite 200
πΊπΈDenver, Colorado, United States
Karmanos Cancer Institute, 4100 John R. street mail Code HW04HO
πΊπΈDetroit, Michigan, United States
Earle A. Chiles Research Institute Providence Cancer Center, 4805 NE Glisan Street, 2N35
πΊπΈPortland, Oregon, United States
Huntsman Cancer Institute, 2000 Circle of Hope Drive
πΊπΈSalt Lake City, Utah, United States
University of California San Diego, 3855 Health Sciences Drive, Mc 0987
πΊπΈLa Jolla, California, United States
Innovative Clinical Research Institute, 15111 Whittier Blvd., Suite 216
πΊπΈWhittier, California, United States
Dana-Farber Cancer Institute, 450 Brookline Avenue
πΊπΈBoston, Massachusetts, United States
Georgetown University Hospital, 3800 Reservoir Rd, NW
πΊπΈWashington, District of Columbia, United States
Stony Brook University Medical Center, 3 Edmund D. Pellegrino Road
πΊπΈStony Brook, New York, United States
NYU Langone Medical Center, 160 East 34th Street, Floor 8
πΊπΈNew York, New York, United States
Thomas Jefferson University, 111 S. 11th Street
πΊπΈPhiladelphia, Pennsylvania, United States
US Oncology-Virginia Cancer Specialists, PC, 8503 Arlington Blvd., Suite 400
πΊπΈFairfax, Virginia, United States
The catholic University of Korea, Seoul St. Mary's hospital, 222 Banpo-daero
π°π·Seoul, Seocho-gu, Korea, Republic of
Antiga Guarderia-Servei d'Oncologia Hospital Vall d'Hebron. P.Vall Hebron 119-129
πͺπΈBarcelona, Spain
Texas Oncology-Tyler, 910 E Houston Street, Suite 100
πΊπΈTyler, Texas, United States
Lynn Cancer Center, 701 NW 13th Street, Floor 2
πΊπΈBoca Raton, Florida, United States
Cleveland Clinic, 9500 Euclid Avenue, G Building
πΊπΈCleveland, Ohio, United States
St. Luke's University Health Network, 701 Ostrum Street, Suite 403
πΊπΈFountain Hill, Pennsylvania, United States
Severance Hospital, Yonsei University Health System 50-1 Yonsei-ro
π°π·Seoul, Seodaemun-gu, Korea, Republic of
Hospital RamΓ³n y Cajal Ctra. Colmenar Viejo Km. 9,1 Planta (-)2 Dcha Oficina de Ensayos ClΓnicos Servicio de OncologΓa MΓ©dica
πͺπΈMadrid, Spain
Hospital Clinico Universitario Valencia Avenida Blasco IbÑñez 17 -8º
πͺπΈValencia, Spain
Taipei Veterans General Hospital, No.201 Sec. 2 Shipai Rd l
π¨π³Taipei City, Beitou District, Taiwan
Asan Medical Center Department of Oncology, 88, Olympic-ro 43-gil
π°π·Seoul, Songpa-gu, Korea, Republic of
Texas Oncology - South Austin, 901 West 38th Street, Suite 200
πΊπΈAustin, Texas, United States