Itacitinib in Combination With Erlotinib in Non Small Cell Lung Cancer Patients With Epidermal Growth Factor Receptor (EGFR) Activating Mutations

March 6, 2019 updated by: Incyte Corporation

A Randomized, Double-blind Phase 2 Study of Itacitinib in Combination With Erlotinib Versus Erlotinib Alone in Subjects With Stage IIIB/ IV or Recurrent Non-Small Cell Lung Cancer (NSCLC) Whose Tumors Have Epidermal Growth Factor Receptor (EGFR) Activating Mutations

The purpose of this study is to determine if Itacitinib in combination with erlotinib is safe and effective in the treatment of nonsquamous non-small cell lung cancer (NSCLC) that is Stage IIIB/Stage IV or recurrent whose tumors have EGFR activating mutations.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

The study consists of an open-label, safety run-in to confirm the safety of Itacitinibin combination with erlotinib in subjects with nonsquamous non-small cell lung cancer (NSCLC) that is Stage IIIB, Stage IV, or recurrent whose tumors have EGFR activating mutations. Subjects in the safety run-in will receive open-label Itacitinib and erlotinib.

In the second part of the study, subjects will be enrolled and randomized to receive erlotinib (open-label) and either Itacitinib or placebo in a blinded manner. The dose of Itacitinib administered will be determined from the data produced in the safety run-in phase.

Treatment will consist of repeating 21-day cycles. Subjects will take erlotinib tablets daily and Itacitinib/placebo will be self-administered daily during the entire cycle.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of nonsquamous NSCLC that is Stage IIIB, Stage IV, or recurrent (including Stage II).
  • Documented evidence of an activating mutation in EGFR in tumor samples (exon 19 deletions or point mutation L858R in exon 21 or point mutations at codon 719).

  • A mGPS of 1 or 2 as defined below:

    • Criteria: C-reactive protein >10 mg/L AND albumin ≥35 g/L Score-1
    • Criteria: C-reactive protein >10 mg L AND albumin <35 g/L Score-2
  • Radiographically measurable or evaluable disease.
  • Life expectancy of at least 12 weeks.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  • Adequate renal, hepatic, and bone marrow function demonstrated by protocol-specified laboratory parameters at the screening visit.

Exclusion Criteria:

  • Known presence of the T790M mutation in EGFR in tumor samples
  • Candidates for curative radiation therapy or surgery.
  • Previous systemic chemotherapy for advanced disease, including EGFR inhibitor therapy, except subjects who received 1 cycle of chemotherapy while waiting to receive EGFR results, who may enroll provided that 21 days have elapsed from end of chemotherapy to the day to the baseline radiographic measurement prior to Cycle 1 Day 1.
  • Distinct or suspected, or history of, pulmonary fibrosis or 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 indolent or Stage I malignancy without sponsor approval.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Itacitinib plus erlotinib
Drug: Itacitinib
tablets to be administered by mouth once daily at dose selected from safety run-in phase
Other Names:
  • INCB039110
Drug: erlotinib
150 mg tablets administered by mouth once daily at total daily dose of 150 mg
Other Names:
  • Tarceva®
Active Comparator: Placebo plus erlotinib
Drug: erlotinib
150 mg tablets administered by mouth once daily at total daily dose of 150 mg
Other Names:
  • Tarceva®
Drug: placebo
matching placebo tablets to be administered by mouth at dose selected from safety run-in phase

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1: Determination of the dose of itacitinib that is safe and tolerable in combination with erlotinib as measured by the number of dose-limiting toxicities (DLTs) observed in the evaluation cohort.
Time Frame: Baseline through Day 21
Subjects will take erlotinib daily and begin dosing with itacitinib once daily (QD) on Cycle 1, Day 1. The safety and tolerability of the regimen will be assessed during the first 21 days of therapy
Baseline through Day 21
Part 2: Overall Survival (OS)
Time Frame: Randomization until death. Approximately 31 months.
Randomization until death. Approximately 31 months.
Part 2: Progression-free survival (PFS)
Time Frame: Randomization to disease progression, or death due to any cause if sooner. Approximately 23 months.
PFS is defined as the time from randomization until the earliest date of disease progression determined by investigator assessment of objective radiographic disease assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause if sooner.
Randomization to disease progression, or death due to any cause if sooner. Approximately 23 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 2: Objective Response
Time Frame: Baseline through end of study. Approximately 31 months.
Objective response determined by radiographic disease assessments per RECIST (v1.1), by investigator assessment
Baseline through end of study. Approximately 31 months.
Part 2: Duration of Response
Time Frame: Baseline through end of study. Approximately 31 months.
Duration of response determined by radiographic disease assessments per RECIST (v1.1), by investigator assessment Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Baseline through end of study. Approximately 31 months.
Part 2: Safety and tolerability of the treatment regimens assessed by a summary of adverse events and clinical laboratory assessments.
Time Frame: Baseline through approximately 30 days post treatment discontinuation. Assessed after approximately 31 months.
Baseline through approximately 30 days post treatment discontinuation. Assessed after approximately 31 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Incyte Corporation

Investigators

  • Study Director: Gerard T. Kennealey, M.D., Incyte Corporation

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2014

Primary Completion (Actual)

September 1, 2015

Study Completion (Actual)

September 1, 2015

Study Registration Dates

First Submitted

January 30, 2015

First Submitted That Met QC Criteria

February 3, 2015

First Posted (Estimate)

February 4, 2015

Study Record Updates

Last Update Posted (Actual)

March 8, 2019

Last Update Submitted That Met QC Criteria

March 6, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INCB 39110-205

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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