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

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02917993
• Other study ID #: INCB 39110-207
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: December 20, 2016
• Est. completion date: December 31, 2025

Study information

• Verified date: January 2024
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 59
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• Itacitinib
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.
• Osimertinib
Osimertinib 80 mg once daily (QD)

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center Department of Oncology, 88, Olympic-ro 43-gil	Seoul	Songpa-gu
Korea, Republic of	Severance Hospital, Yonsei University Health System 50-1 Yonsei-ro	Seoul	Seodaemun-gu
Korea, Republic of	The catholic University of Korea, Seoul St. Mary's hospital, 222 Banpo-daero	Seoul	Seocho-gu
Spain	Antiga Guarderia-Servei d'Oncologia Hospital Vall d'Hebron. P.Vall Hebron 119-129	Barcelona
Spain	Hospital Ramón y Cajal Ctra. Colmenar Viejo Km. 9,1 Planta (-)2 Dcha Oficina de Ensayos Clínicos Servicio de Oncología Médica	Madrid
Spain	Hospital Clinico Universitario Valencia Avenida Blasco Ibáñez 17 -8º	Valencia
Taiwan	National Taiwan University Hospital, 7 Zhongshan South Road	Taipei	Zhongzheng District
Taiwan	Taipei Veterans General Hospital, No.201 Sec. 2 Shipai Rd l	Taipei City	Beitou District
United States	Texas Oncology - South Austin, 901 West 38th Street, Suite 200	Austin	Texas
United States	Lynn Cancer Center, 701 NW 13th Street, Floor 2	Boca Raton	Florida
United States	Dana-Farber Cancer Institute, 450 Brookline Avenue	Boston	Massachusetts
United States	Cleveland Clinic, 9500 Euclid Avenue, G Building	Cleveland	Ohio
United States	Rocky Mountain Cancer Center, 1800 Williams Street, Suite 200	Denver	Colorado
United States	Henry Ford Health System, 2799 W Grand Blvd.	Detroit	Michigan
United States	Karmanos Cancer Institute, 4100 John R. street mail Code HW04HO	Detroit	Michigan
United States	US Oncology-Virginia Cancer Specialists, PC, 8503 Arlington Blvd., Suite 400	Fairfax	Virginia
United States	St. Luke's University Health Network, 701 Ostrum Street, Suite 403	Fountain Hill	Pennsylvania
United States	University of Texas -MD Anderson Cancer Center, 1515 Holcombe Blvd.	Houston	Texas
United States	University of California San Diego, 3855 Health Sciences Drive, Mc 0987	La Jolla	California
United States	West Virginia University Cancer Institute, 1 Medical Center Drive	Morgantown	West Virginia
United States	NYU Langone Medical Center, 160 East 34th Street, Floor 8	New York	New York
United States	Thomas Jefferson University, 111 S. 11th Street	Philadelphia	Pennsylvania
United States	Earle A. Chiles Research Institute Providence Cancer Center, 4805 NE Glisan Street, 2N35	Portland	Oregon
United States	Valley Hospital, 223 N Van Dien Avenue	Ridgewood	New Jersey
United States	Huntsman Cancer Institute, 2000 Circle of Hope Drive	Salt Lake City	Utah
United States	Texas Oncology - San Antonio Medical, 5206 Research Drive	San Antonio	Texas
United States	University California San Francisco Thoracic Surgery and Oncology Clinic, 1600 Divisadero Street, Floor 4	San Francisco	California
United States	Stony Brook University Medical Center, 3 Edmund D. Pellegrino Road	Stony Brook	New York
United States	Texas Oncology-Tyler, 910 E Houston Street, Suite 100	Tyler	Texas
United States	Georgetown University Hospital, 3800 Reservoir Rd, NW	Washington	District of Columbia
United States	Innovative Clinical Research Institute, 15111 Whittier Blvd., Suite 216	Whittier	California

Sponsors (2)

Lead Sponsor	Collaborator
Incyte Corporation	AstraZeneca

Countries where clinical trial is conducted

United States,  Korea, Republic of,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Frequency, severity, and duration of adverse events (AEs)		From screening through 30-35 days after end of treatment, approximately 2 years.
Primary	Phase 1: Number of subjects with dose-limiting toxicities (DLTs)		Day 1 through Day 28
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	Phase 2: Overall survival (OS)		Interval from the first day of study treatment until death due to any cause, approximately 3 years.
Secondary	Phase 2: Frequency, severity, and duration of AEs		From screening through 30-35 days after end of treatment, approximately 2 years.