A Study of EGF816 and Gefitinib in TKI-naïve EGFR-mutant Non-Small Cell Lung Cancer

NCT03292133 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-291
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying a combination of drugs as a possible treatment for EGFR mutation-positive lung cancer. The drugs involved in this study are:

• EGF816
• Gefitinib

Conditions

Lung Cancer

Keywords

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 9 Months Progression Free Rate

  The percentage of participants that are free from objective disease progression or death at 9 months after the start treatment. Progression is evaluated using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

  9 months

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  4 years and 4 months

• Median Overall Survival

  6 years

• Median Progression Free Survival (PFS)

  4.2 years

• Summary of Treatment-related Adverse Events

  Start of treatment through 30 days after the end of treatment (max 4 years and 5 months)

Study Arms (1)

EGF816 + Gefitinib

EXPERIMENTAL

* All patients will receive gefitinib orally once daily * EGF816 will be administered orally once daily * Participant will be requested to maintain a medication diary of each dose of medication

Drug: EGF816; Drug: Gefitinib

Interventions

EGF816 DRUG

EGF816 is an inhibitor which target a specific mutation in cancer and may stop tumors growing and multiplying

EGF816 + Gefitinib

Gefitinib DRUG

Gefitinib is an inhibitor which target a specific mutation in cancer and may stop tumors growing and multiplying

Also known as: Iressa

EGF816 + Gefitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have a pathologically-confirmed diagnosis of non-small cell lung cancer (NSCLC).
• Participants must have advanced disease - either stage IV disease, stage IIIB disease not amenable to definitive multi-modality therapy, or recurrent disease after a prior diagnosis of stage I-III disease. All staging is via the American Joint Committee on Cancer (AJCC)/IASLC 7th edition proposed staging criteria
• An EGFR sensitizing mutation must be detected in tumor tissue. Specifically, patients harboring the most common mutations, deletions in exon 19 or the L858R mutation in exon 21 are eligible. Other EGFR sensitizing mutations may be eligible after discussion with the principal investigator. Patients may be enrolled in the study based on an activating EGFR mutation detected by a CLIA-certified tissue or plasma-based assay, but will be required to undergo a mandatory tumor biopsy during study screening.
• Participants must have measurable disease, per RECIST 1.1. See Section 11 for the evaluation of measurable disease.
• Patients in the six patient safety run-in cohort may have had a prior EGFR TKI in the metastatic setting (to allow for patients who started initial therapy at an outside hospital), but treatment duration must have been less than three months. After the initial six-patient safety run-in, no prior EGFR TKI therapy in the metastatic setting is allowed. An EGFR TKI given in the adjuvant setting (i.e. with no measurable disease at the time of administration) is allowable provided the subject has been off of EGFR TKI therapy for at least six months at the time of enrollment.
• Patients may have had no more than one prior line of chemotherapy or immunotherapy in the metastatic setting. At least 14 days must have elapsed from the last chemo/immunotherapy administration until the start of protocol treatment, and patients must have recovered from the side effects of any of these agents.
• Patients must be screened for HBV. Patients who are either HBsAg positive or HBV-DNA positive must be willing and able to take antiviral therapy 1-2 weeks prior to 1st dose of study treatment and continue on antiviral therapy for at least 4 weeks after the last dose of EGF816. Additional management of the patients would be provided by a physician with expertise in management of HBV, if needed. Patients must have negative hepatitis C antibody (HCV-Ab) or positive HCV-Ab but undetectable level of HCV-RNA. Note: patients with detectable HCV-RNA are not eligible for the study.
• Patients must receive insurance approval for or be willing to pay for commercial gefitinib.
• Age \>/= 18 years.
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
• Life expectancy of greater than 12 weeks.
• Participants must have normal organ and marrow function as defined below:
• Leukocytes ≥3,000/mcL
• Absolute neutrophil count ≥1,500/mcL
• Platelets ≥100,000/mcL

You may not qualify if:

• Participants with clinically active or symptomatic interstitial lung disease or interstitial pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention) and patients with history of clinically significant interstitial lung disease or radiation pneumonitis.
• Patients with clinically symptomatic brain metastases or leptomeningeal disease. Patients may be on a stable dose of corticosteroids to control brain metastases if they have been on a stable dose for two weeks prior to study treatment and are clinically asymptomatic.
• Patients who have had radiation to the lung fields within four weeks of starting treatment. For patients receiving palliative radiation to thoracic vertebrae, ribs or other sites where the radiation field includes the lungs, radiation must be completed at least two weeks before starting treatment. For all palliative radiation to all other sites, at least 7 days must have elapsed prior to starting to treatment. At least six months must have elapsed from radiation given with curative intent.
• Patients who have had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 2 weeks prior to starting study drug or who have not recovered from side effects of such procedure. Video-assisted thoracic surgery (VATS) and mediastinoscopy will not be counted as major surgery and patients can be enrolled in the study ≥1 week after the procedure.
• Patients unable or unwilling to undergo a biopsy for research during the screening period, 2-3 weeks into the course of therapy and at the time of progression.
• Patients with a second, clinically active, cancer. Patients with second cancers which have been treated with curative intent and/or are currently inactive are allowed.
• Patients who have undergone a bone marrow or solid organ transplant.
• Known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory).
• Participants who are receiving any other investigational agents. Patients previously treated with investigational agents must complete a washout period of at least one week or five half-lives, whichever is longer, before starting treatment.
• Patients receiving concomitant immunosuppressive agents or chronic corticosteroid use, except those on steroid to control brain metastases, those on topical or inhaled steroids, or steroids given via local injection.
• Patients with clinically significant, uncontrolled cardiovascular disease, such as:
• Unstable angina within 6 months prior to screening
• Myocardial infarction within 6 months prior to screening
• Patients with a history of documented congestive heart failure (New York Heart Association functional classification III-IV)
• Peripheral vascular disease

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Novartis: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

nazartinib; Gefitinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

While the original sample size was planned to be 36 patients, only 11 patients were enrolled, as the study was terminated early due to slow accrual.

Results Point of Contact

• Title: Zofia Piotrowska, MD
• Organization: Massachusetts General Hospital

Zofia.Piotrowska@MGH.HARVARD.EDU

6176439707

Study Officials

• Zofia Piotrowska, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 21, 2017
• First Posted: September 25, 2017
• Study Start: October 31, 2017
• Primary Completion: December 31, 2021
• Study Completion: March 4, 2025
• Last Updated: June 10, 2025
• Results First Posted: June 10, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)