Clinical trial NCT02917993: An Open-Label Phase 1/2 Study of Itacitinib in Combination With Osimertinib in Subjects With Non-Small Cell Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Lung Cancer
Keywords: non-small cell lung cancer
locally advanced
metastatic
epidermal growth factor receptor (EGFR) inhibition
Janus kinase inhibition
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2016-09-28
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1: Frequency, severity, and duration of adverse events (AEs)
timeFrame: From screening through 30-35 days after end of treatment, approximately 2 years.
measure: Phase 1: Number of subjects with dose-limiting toxicities (DLTs)
timeFrame: Day 1 through Day 28
measure: Phase 2: Objective response rate (ORR) based on RECIST v1.1
timeFrame: Screening and 8-week intervals throughout the study, approximately 2 years.
Secondary outcomes:
measure: Phase 1 and Phase 2: Maximum plasma concentration (Cmax) of itacitinib and osimertinib when administered in combination
timeFrame: Measured at protocol-defined study visits from Cycle 1 Day 1 through Cycle 1 Day 28.
measure: Phase 1 and Phase 2: Area under the plasma concentration-time curve (AUC) of Itacitinib and osimertinib when administered in combination
timeFrame: Measured at protocol-defined study visits from Cycle 1 Day 1 through Cycle 1 Day 28.
measure: Phase 2: Depth of response (DpR) based on RECIST v1.1
timeFrame: Screening and 8-week intervals throughout the study, approximately 2 years.
measure: Phase 2: Progression-free survival (PFS)
timeFrame: Interval from the first day of study treatment until disease progression or death due to any cause, approximately 3 years.
measure: Phase 2: Overall survival (OS)
timeFrame: Interval from the first day of study treatment until death due to any cause, approximately 3 years.
measure: Phase 2: Frequency, severity, and duration of AEs
timeFrame: From screening through 30-35 days after end of treatment, approximately 2 years.
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego, 3855 Health Sciences Drive, Mc 0987
state: California
city: San Francisco
country: United States
facility: University California San Francisco Thoracic Surgery and Oncology Clinic, 1600 Divisadero Street, Floor 4
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute, 15111 Whittier Blvd., Suite 216
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Center, 1800 Williams Street, Suite 200
state: Colorado
city: Washington
country: United States
facility: Georgetown University Hospital, 3800 Reservoir Rd, NW
state: District of Columbia
city: Boca Raton
country: United States
facility: Lynn Cancer Center, 701 NW 13th Street, Floor 2
state: Florida
city: Boston
country: United States
facility: Dana-Farber Cancer Institute, 450 Brookline Avenue
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System, 2799 W Grand Blvd.
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute, 4100 John R. street mail Code HW04HO
state: Michigan
city: Ridgewood
country: United States
facility: Valley Hospital, 223 N Van Dien Avenue
state: New Jersey
city: New York
country: United States
facility: NYU Langone Medical Center, 160 East 34th Street, Floor 8
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center, 3 Edmund D. Pellegrino Road
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic, 9500 Euclid Avenue, G Building
state: Ohio
city: Portland
country: United States
facility: Earle A. Chiles Research Institute Providence Cancer Center, 4805 NE Glisan Street, 2N35
state: Oregon
city: Fountain Hill
country: United States
facility: St. Luke's University Health Network, 701 Ostrum Street, Suite 403
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University, 111 S. 11th Street
state: Pennsylvania
city: Austin
country: United States
facility: Texas Oncology - South Austin, 901 West 38th Street, Suite 200
state: Texas
city: Houston
country: United States
facility: University of Texas -MD Anderson Cancer Center, 1515 Holcombe Blvd.
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Medical, 5206 Research Drive
state: Texas
city: Tyler
country: United States
facility: Texas Oncology-Tyler, 910 E Houston Street, Suite 100
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute, 2000 Circle of Hope Drive
state: Utah
city: Fairfax
country: United States
facility: US Oncology-Virginia Cancer Specialists, PC, 8503 Arlington Blvd., Suite 400
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University Cancer Institute, 1 Medical Center Drive
state: West Virginia
city: Seoul
country: Korea, Republic of
facility: The catholic University of Korea, Seoul St. Mary's hospital, 222 Banpo-daero
state: Seocho-gu
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System 50-1 Yonsei-ro
state: Seodaemun-gu
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center Department of Oncology, 88, Olympic-ro 43-gil
state: Songpa-gu
city: Barcelona
country: Spain
facility: Antiga Guarderia-Servei d'Oncologia Hospital Vall d'Hebron. P.Vall Hebron 119-129
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal Ctra. Colmenar Viejo Km. 9,1 Planta (-)2 Dcha Oficina de Ensayos Clínicos Servicio de Oncología Médica
city: Valencia
country: Spain
facility: Hospital Clinico Universitario Valencia Avenida Blasco Ibáñez 17 -8º
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital, No.201 Sec. 2 Shipai Rd l
state: Beitou District
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital, 7 Zhongshan South Road
state: Zhongzheng District
Study officials:
affiliation: Incyte Corporation
name: Peter Langmuir
role: STUDY_DIRECTOR
References: