Clinical Trials /

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



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

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:



Phase 2

Trial Eligibility



  • Brief Title: A Study of EGF816 and Gefitinib in TKI-naïve EGFR-mutant Non-Small Cell Lung Cancer
  • Official Title: A Phase 2 Study of EGF816 and Gefitinib in TKI-naïve EGFR-mutant Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 17-291
  • NCT ID: NCT03292133


  • Lung Cancer


EGF816EGF816 + Gefitinib
GefitinibIressaEGF816 + Gefitinib


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

Detailed Description

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational drug to learn whether the drug works in treating a
      specific disease or patient population. "Investigational" means that the drug or drugs are
      being studied and have not been approved together for patients.

      The FDA (the U.S. Food and Drug Administration) has approved gefitinib as a treatment option
      for EGFR mutation-positive lung cancer.

      The FDA has not approved EGF816 as a treatment for any disease at this time.

      In this research study, the investigators are studying the safety and efficacy of the
      combination of the study drugs EGF816 and gefitinib.

      Both EGF816 and gefitinib are inhibitors which target a specific mutation in cancer and may
      stop tumors growing and multiplying.

Trial Arms

EGF816 + GefitinibExperimentalAll 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
  • EGF816
  • Gefitinib

Eligibility Criteria

        Inclusion Criteria:

          -  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

          -  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

               -  Total bilirubin >1.5 x upper limit of normal (ULN)

                  *For patients with Gilbert's syndrome total bilirubin >3.0 x ULN

               -  AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal; for patients with
                  known hepatic metastases AST and/or ALT > 5x ULN

               -  Creatinine ≤1.5 × institutional upper limit of normal

          -  The effects of EGF816 and gefitinib on the developing human fetus are unknown. For
             this reason, women of child-bearing potential and men must agree to use highly
             effective contraception during the study and for 3 months after stopping the study
             treatment. Highly effective contraception methods include:

               -  Total abstinence (when this is in line with the preferred and usual lifestyle of
                  the subject. Periodic abstinence (e.g., calendar, ovulation, symptom thermal,
                  postovulation methods) and withdrawal are not acceptable methods of contraception

               -  Female sterilization (have had surgical bilateral oophorectomy with or without
                  hysterectomy) or tubal ligation at least six weeks before taking study treatment.
                  In case of oophorectomy alone, only when the reproductive status of the woman has
                  been confirmed by follow up hormone level assessment

               -  Male Partner: male sterilization (at least 6 months prior to screening). For
                  female subjects on the study the vasectomized male partner should be the sole
                  partner for that subject.

               -  Combination of any two of the following (a+b or a+c, or b+c):

               -  A. Use of oral, injected or implanted hormonal methods of contraception or other
                  forms of hormonal contraception that have comparable efficacy (failure rate <1%),
                  for example hormone vaginal ring or transdermal hormone contraception.

               -  B. Placement of an intrauterine device (IUD) or intrauterine system (IUS)

               -  C. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
                  cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.

               -  D. In case of use of oral contraception women should have been stable on the same
                  pill for a minimum of 30 days before taking study treatment.

               -  Women are considered post-menopausal and not of childbearing potential if they
                  have had 12 months of natural (spontaneous) amenorrhea with an appropriate
                  clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have
                  had surgical bilateral oophorectomy (with or without hysterectomy) or tubal
                  ligation at least six weeks ago. In the case of oophorectomy alone, only when the
                  reproductive status of the woman has been confirmed by follow up hormone level
                  assessment is she considered not of childbearing potential.

               -  Sexually active males must agree to use a condom during intercourse while taking
                  drug and for 3 months after stopping treatment; men should not father a child in
                  this period. A condom is required to be used also by vasectomized men in order to
                  prevent delivery of the drug via seminal fluid.

          -  Ability to understand and the willingness to sign a written informed consent document.
             Written informed consent must be obtained prior to any screening procedures.

        Exclusion Criteria:

          -  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

          -  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

               -  Patients with uncontrolled hypertension defined as a Systolic Blood Pressure
                  (SBP) ≥ 160 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, with or
                  without anti-hypertensive medication. Initiation or adjustment of
                  antihypertensive medication(s) is allowed prior to screening

               -  Ventricular arrhythmias

               -  Supraventricular and nodal arrhythmias not controlled with medication

               -  Other cardiac arrhythmia not controlled with medication

               -  Patients with corrected QT (QTc) ≥450 ms (male patients) or ≥460 ms (female
                  patients) using Fridericia correction (QTcF) on the screening ECG (using
                  triplicate ECGs)

               -  Patients with history of congenital long QT syndrome or history of torsade de

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to EGF816 or gefitinib.

          -  Participants receiving any medications or substances that are strong inhibitors or
             inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly
             changing, it is important to regularly consult a frequently-updated list such as
   ; medical reference texts such as
             the Physicians' Desk Reference may also provide this information. As part of the
             enrollment/informed consent procedures, the patient will be counseled on the risk of
             interactions with other agents, and what to do if new medications need to be
             prescribed or if the patient is considering a new over-the-counter medicine or herbal

          -  Unable or unwilling to swallow tablets or capsules.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnant women are excluded from this study because the effects of EGF816 and
             gefitinib on a developing fetus are unknown. Because there is an unknown but potential
             risk for adverse events in nursing infants secondary to treatment of the mother with
             EGF816 or gefitinib, breastfeeding should be discontinued if the mother is treated
             with EGF816 and gefitinib
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival at 9 months
Time Frame:9 months
Safety Issue:
Description:The number of participants that are free from objective disease progression or death at 9 months. 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).

Secondary Outcome Measures

Measure:Response Rate
Time Frame:2 years
Safety Issue:
Description:The number of participants that achieve either a complete response (CR) or a partial response (PR). Response is evaluated using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. All CRs and PRs must be confirmed by a second assessment not earlier than 4 weeks after the criteria for response are first met.
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:Overall survival is defined as time from the start of treatment until death. Overall survival will be analyzed using the Kaplan-Meier method.
Measure:Safety and Tolerability of the EGF816/gefitinib combination (Summary of the adverse events experienced by study participants as evaluated by CTCAE v4)
Time Frame:2 years
Safety Issue:
Description:Summary of the adverse events experienced by study participants as evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v4.


Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • Lung Cancer

Last Updated

December 16, 2020