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

Sponsor

Incyte Corporation (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02917993

Collaborator

AstraZeneca (Industry)

Enrollment

Locations

Arm

Anticipated Duration (Months)

1.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: Itacitinib Drug: Osimertinib	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

59 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 20, 2016

Anticipated Primary Completion Date :

Dec 21, 2022

Anticipated Study Completion Date :

Dec 21, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Itacitinib + osimertinib	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. Other Names: INCB039110 Drug: Osimertinib Osimertinib 80 mg once daily (QD)

Arm

Intervention/Treatment

Experimental: Itacitinib + osimertinib

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.

Other Names:

INCB039110

Drug: Osimertinib

Osimertinib 80 mg once daily (QD)

Outcome Measures

Primary Outcome Measures

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

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.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Diego, 3855 Health Sciences Drive, Mc 0987	La Jolla	California	United States	92093
2	University California San Francisco Thoracic Surgery and Oncology Clinic, 1600 Divisadero Street, Floor 4	San Francisco	California	United States	94115
3	Innovative Clinical Research Institute, 15111 Whittier Blvd., Suite 216	Whittier	California	United States	90603
4	Rocky Mountain Cancer Center, 1800 Williams Street, Suite 200	Denver	Colorado	United States	80124
5	Georgetown University Hospital, 3800 Reservoir Rd, NW	Washington	District of Columbia	United States	20007
6	Lynn Cancer Center, 701 NW 13th Street, Floor 2	Boca Raton	Florida	United States	33486
7	Dana-Farber Cancer Institute, 450 Brookline Avenue	Boston	Massachusetts	United States	02215
8	Henry Ford Health System, 2799 W Grand Blvd.	Detroit	Michigan	United States	48202
9	Karmanos Cancer Institute, 4100 John R. street mail Code HW04HO	Detroit	Michigan	United States	48202
10	Valley Hospital, 223 N Van Dien Avenue	Ridgewood	New Jersey	United States	07450
11	NYU Langone Medical Center, 160 East 34th Street, Floor 8	New York	New York	United States	10016
12	Stony Brook University Medical Center, 3 Edmund D. Pellegrino Road	Stony Brook	New York	United States	11794
13	Cleveland Clinic, 9500 Euclid Avenue, G Building	Cleveland	Ohio	United States	44195
14	Earle A. Chiles Research Institute Providence Cancer Center, 4805 NE Glisan Street, 2N35	Portland	Oregon	United States	97213
15	St. Luke's University Health Network, 701 Ostrum Street, Suite 403	Fountain Hill	Pennsylvania	United States	18015
16	Thomas Jefferson University, 111 S. 11th Street	Philadelphia	Pennsylvania	United States	19107
17	Texas Oncology - South Austin, 901 West 38th Street, Suite 200	Austin	Texas	United States	78705
18	University of Texas -MD Anderson Cancer Center, 1515 Holcombe Blvd.	Houston	Texas	United States	77030
19	Texas Oncology - San Antonio Medical, 5206 Research Drive	San Antonio	Texas	United States	78240
20	Texas Oncology-Tyler, 910 E Houston Street, Suite 100	Tyler	Texas	United States	75702
21	Huntsman Cancer Institute, 2000 Circle of Hope Drive	Salt Lake City	Utah	United States	84112
22	US Oncology-Virginia Cancer Specialists, PC, 8503 Arlington Blvd., Suite 400	Fairfax	Virginia	United States	22031
23	West Virginia University Cancer Institute, 1 Medical Center Drive	Morgantown	West Virginia	United States	26506
24	The catholic University of Korea, Seoul St. Mary's hospital, 222 Banpo-daero	Seoul	Seocho-gu	Korea, Republic of	06591
25	Severance Hospital, Yonsei University Health System 50-1 Yonsei-ro	Seoul	Seodaemun-gu	Korea, Republic of	03722
26	Asan Medical Center Department of Oncology, 88, Olympic-ro 43-gil	Seoul	Songpa-gu	Korea, Republic of	05505
27	Antiga Guarderia-Servei d'Oncologia Hospital Vall d'Hebron. P.Vall Hebron 119-129	Barcelona		Spain	08035
28	Hospital Ramón y Cajal Ctra. Colmenar Viejo Km. 9,1 Planta (-)2 Dcha Oficina de Ensayos Clínicos Servicio de Oncología Médica	Madrid		Spain	28034
29	Hospital Clinico Universitario Valencia Avenida Blasco Ibáñez 17 -8º	Valencia		Spain	46010
30	Taipei Veterans General Hospital, No.201 Sec. 2 Shipai Rd l	Taipei City	Beitou District	Taiwan	11217
31	National Taiwan University Hospital, 7 Zhongshan South Road	Taipei	Zhongzheng District	Taiwan	10002