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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: Itacitinib; Drug: Osimertinib

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.
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.

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Collaborators: AstraZeneca
• Investigators: Study Director: Peter Langmuir, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2016
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: September 26, 2016
• First Submitted That Met QC Criteria: September 26, 2016
• First Posted (Estimated): September 28, 2016

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: non-small cell lung cancer; metastatic; locally advanced; epidermal growth factor receptor (EGFR) inhibition; Janus kinase inhibition
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Osimertinib
• Other Study ID Numbers: INCB 39110-207