Clinical Trials List
Protocol NumberCEGF816X2102
NCT Number(ClinicalTrials.gov Identfier)NCT03333343
Completed
2017-11-01 - 2021-12-31
Others
Recruiting2
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
A Phase Ib, Open Label, Multi-center Study to Characterize the Safety, Tolerability and Preliminary Efficacy of EGF816 in Combination With Selected Targeted Agents in EGFR Mutant NSCLC
-
Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
-
Sponsor
Novartis Pharmaceuticals
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/03/01
Investigators and Locations
Co-Principal Investigator
- Wen-Pin Su Division of Hematology & Oncology
- Jui-Hung Tsai Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
- Wu-Chou Su Division of Hematology & Oncology
- Wei-Pang Chung Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- Chia-Chi Lin Division of Hematology & Oncology
- 陳冠宇 Division of General Internal Medicine
- 林育麟 醫學研究部
- 楊景堯 Division of General Internal Medicine
- Chong-Jen Yu Division of General Internal Medicine
- 廖唯昱 Division of General Internal Medicine
- 徐偉勛 國家及卓越臨床試驗與研究中心
- JIN-YUAN SHIH Division of General Internal Medicine
- 許嘉林 Division of General Internal Medicine
- 蔡子修 Division of General Internal Medicine
- Jih-Hsiang Lee 醫學研究部
- CHAO-CHI HO CHAO-CHI HO Division of General Internal Medicine
- 廖斌志 Division of Hematology & Oncology
- 吳尚俊 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
EGFR-mutant Non-small Cell Lung Cancer
Objectives
Primary
-To characterize the safety and tolerability of EGF816 in combination with ribociclib, trametinib, or LXH254 in patients with advanced EGFR-mutant NSCLC in 1st line or ≥ 2nd line T790M+, 3rd gen EGFR TKI-naive and identify a recommended dose and regimen.
-To estimate the preliminary anti-tumor activity of the addition of ribociclib, trametinib, LXH254, gefitinib, or INC280 to EGF816 in patients with advanced EGFRmutant NSCLC in 1st line or ≥ 2nd line T790M+, 3rd gen EGFR TKI-naïve.
Secondary
-To assess the preliminary anti-tumor activity of EGF816 single agent given for 5 cycles followed by the addition of ribociclib, trametinib, LXH254, gefitinib, or INC280 to EGF816 in advanced EGFR-mutant NSCLC in 1st line or 2nd line and beyond T790M+,
3rd gen EGFR TKI-naive (endpoints ORR, PFS, DOR, DCR).
-To characterize the PK properties of EGF816 as a single agent and in combination with: ribociclib, trametinib, LXH254, gefitinib, and INC280.
Test Drug
EGF816、LXH254、INC280、Kisqali(LEE011)、Mekinist(TMT212) & IRESSA
Active Ingredient
Gefitinib
INC280
LXH254
Ribociclib (LEE011)
Trametinib (TMT212)
INC280
LXH254
Ribociclib (LEE011)
Trametinib (TMT212)
Dosage Form
EGF816: film-coated tablet
LXH254: tablet
INC280: film-coated tablet
LEE011: hard gelatin capsules
TMT212: film-coated tablets
Gefitinib: film-coated tablets
LXH254: tablet
INC280: film-coated tablet
LEE011: hard gelatin capsules
TMT212: film-coated tablets
Gefitinib: film-coated tablets
Dosage
EGF816 25mg & 50mg/tablet
LXH254 50mg & 100mg/tablet
INC280 150mg & 200mg/tablet
LEE011 50mg & 200mg/capsule
TMT212 0.5mg & 2mg/tablet
Gefitinib 250mg/tablet
LXH254 50mg & 100mg/tablet
INC280 150mg & 200mg/tablet
LEE011 50mg & 200mg/capsule
TMT212 0.5mg & 2mg/tablet
Gefitinib 250mg/tablet
Endpoints
Primary Outcome Measures :
Number of patients with adverse events and serious adverse events [ Time Frame: Every day until study end, approximately 4 years ]
Assess safety and tolerability including incidence of dose limiting toxicities, adverse events, and serious adverse events.
ORR2 [ Time Frame: Every 8-12 weeks until study ends, approximately 4 years ]
Modified objective response rate (ORR2) per RECIST v1.1 (taking as baseline the most recent assessment prior to initiating combination)
Number of patients with adverse events and serious adverse events [ Time Frame: Every day until study end, approximately 4 years ]
Assess safety and tolerability including incidence of dose limiting toxicities, adverse events, and serious adverse events.
ORR2 [ Time Frame: Every 8-12 weeks until study ends, approximately 4 years ]
Modified objective response rate (ORR2) per RECIST v1.1 (taking as baseline the most recent assessment prior to initiating combination)
Inclution Criteria
Inclusion criteria
Patients eligible for inclusion in this study must meet all of the following criteria:
1. Able to understand and voluntarily sign the ICF and to comply with the study visit
schedule and the other protocol requirements. Written informed consent must be obtained
prior to any study specific procedures that are not part of standard of care. If consent
cannot be expressed in writing, it must be formally documented and witnessed, ideally via
an independent trusted witness.
For Japan only: written consent is necessary both from the patient and his/her legal
representative if he/she is under the age of 20 years.
2. Patient (male or female) ≥ 18 years of age.
3. Patients must have histologically or cytologically confirmed locally advanced (defined as
stage IIIB that is not amenable to definitive treatment with chemoradiation) or metastatic
(stage IV) EGFR mutant (ex19del, L858R) NSCLC.
4. Requirements of EGFR mutation status and prior lines of treatment:
Treatment-naive patients, who have locally advanced or metastatic NSCLC with
EGFR sensitizing mutation (e.g., L858R and/or ex19del), have not received any
systemic antineoplastic therapy for advanced NSCLC and are eligible to receive
EGFR TKI treatment. Patients with EGFR exon 20 insertion/duplication are not
eligible. Note: patients who have received only one cycle of chemotherapy in the
advanced setting are allowed.
Patients who have locally advanced or metastatic NSCLC with EGFR sensitizing
mutation AND an acquired T790M mutation (e.g., L858R and/or ex19del, T790M+)
following progression on prior treatment with a 1st-generation EGFR TKI (e.g.
erlotinib, gefitinib or icotinib) or 2nd-generation EGFR TKI (e.g., afatinib or
dacomitinib). These patients may not have received more than 4 prior lines of
antineoplastic therapy in the advanced setting, including EGFR TKI, and may not
have received any agent targeting EGFR T790M mutation (i.e. 3rd-generation EGFR
TKI). EGFR mutation testing must be performed after progression on EGFR TKI.
Patients who have locally advanced or metastatic NSCLC with EGFR sensitizing
mutation and a “de novo” T790M mutation (i.e. no prior treatment with any agent
known to inhibit EGFR including EGFR TKI). These patients may not have received
more than 3 prior lines of antineoplastic therapy in the advanced setting, and may not
have received any prior 3rd generation EGFR TKI.
5. ECOG performance status: 0-1
6. Presence of at least one measurable lesion according to RECIST v1.1 per Investigator
assessment. A previously irradiated site lesion may be counted as a target lesion only if
there is clear sign of progression since the irradiation (see Appendix 1)
7. 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
EGF816 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.
8. Patients must be screened for HCV. 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.
9. Patients must be willing and able to comply with scheduled visits, treatment plans,
laboratory tests and other study procedures.
10. Patients must have a site of disease amenable to biopsy, and be a candidate for tumor
biopsy according to the treating institution’s guidelines. Patients must be willing to
undergo a new tumor biopsy during therapy on this study, and at screening if an archival
tumor sample obtained since the diagnosis of advanced disease (first-line (1L) patients) or
since last treatment failure (≥ second line (2L+) patients) is not available.
Patients eligible for inclusion in this study must meet all of the following criteria:
1. Able to understand and voluntarily sign the ICF and to comply with the study visit
schedule and the other protocol requirements. Written informed consent must be obtained
prior to any study specific procedures that are not part of standard of care. If consent
cannot be expressed in writing, it must be formally documented and witnessed, ideally via
an independent trusted witness.
For Japan only: written consent is necessary both from the patient and his/her legal
representative if he/she is under the age of 20 years.
2. Patient (male or female) ≥ 18 years of age.
3. Patients must have histologically or cytologically confirmed locally advanced (defined as
stage IIIB that is not amenable to definitive treatment with chemoradiation) or metastatic
(stage IV) EGFR mutant (ex19del, L858R) NSCLC.
4. Requirements of EGFR mutation status and prior lines of treatment:
Treatment-naive patients, who have locally advanced or metastatic NSCLC with
EGFR sensitizing mutation (e.g., L858R and/or ex19del), have not received any
systemic antineoplastic therapy for advanced NSCLC and are eligible to receive
EGFR TKI treatment. Patients with EGFR exon 20 insertion/duplication are not
eligible. Note: patients who have received only one cycle of chemotherapy in the
advanced setting are allowed.
Patients who have locally advanced or metastatic NSCLC with EGFR sensitizing
mutation AND an acquired T790M mutation (e.g., L858R and/or ex19del, T790M+)
following progression on prior treatment with a 1st-generation EGFR TKI (e.g.
erlotinib, gefitinib or icotinib) or 2nd-generation EGFR TKI (e.g., afatinib or
dacomitinib). These patients may not have received more than 4 prior lines of
antineoplastic therapy in the advanced setting, including EGFR TKI, and may not
have received any agent targeting EGFR T790M mutation (i.e. 3rd-generation EGFR
TKI). EGFR mutation testing must be performed after progression on EGFR TKI.
Patients who have locally advanced or metastatic NSCLC with EGFR sensitizing
mutation and a “de novo” T790M mutation (i.e. no prior treatment with any agent
known to inhibit EGFR including EGFR TKI). These patients may not have received
more than 3 prior lines of antineoplastic therapy in the advanced setting, and may not
have received any prior 3rd generation EGFR TKI.
5. ECOG performance status: 0-1
6. Presence of at least one measurable lesion according to RECIST v1.1 per Investigator
assessment. A previously irradiated site lesion may be counted as a target lesion only if
there is clear sign of progression since the irradiation (see Appendix 1)
7. 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
EGF816 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.
8. Patients must be screened for HCV. 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.
9. Patients must be willing and able to comply with scheduled visits, treatment plans,
laboratory tests and other study procedures.
10. Patients must have a site of disease amenable to biopsy, and be a candidate for tumor
biopsy according to the treating institution’s guidelines. Patients must be willing to
undergo a new tumor biopsy during therapy on this study, and at screening if an archival
tumor sample obtained since the diagnosis of advanced disease (first-line (1L) patients) or
since last treatment failure (≥ second line (2L+) patients) is not available.
Exclusion Criteria
Exclusion criteria
Patients eligible for this study must not meet any of the following criteria:
For All patients (unless otherwise specified):
1. Patients with a history or presence of interstitial lung disease or interstitial pneumonitis,
including clinically significant radiation pneumonitis (i.e. affecting activities of daily
living or requiring therapeutic intervention).
2. Patients with unstable brain metastases. Patients with controlled brain metastases may
participate in the trial. They must complete any planned radiation therapy and/or
surgery >2 weeks prior to the first dose of study treatment and remain asymptomatic.
Patients on steroids must have been on a stable or decreasing low dose for 2 weeks prior to
initiating study treatment.
3. Patients with a history of another malignancy. Exception: patients who have been diseasefree for 3 years, or patients with a history of completely resected in-situ carcinoma of any
type, basal or squamous cell skin carcinoma, or stage IA melanoma that has been cured,
are eligible.
4. Patients who have undergone a bone marrow or solid organ transplant.
5. Patients with a known history of human immunodeficiency virus (HIV) seropositivity
(HIV testing is not mandatory).
6. Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use
at the time of study entry except for control of brain metastases, or in form of topical
applications, inhaled sprays, eye drops or local injections.
7. Patients with clinically significant, uncontrolled heart 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
Left ventricular ejection fraction (LVEF) < 50% or below the institutional standard
lower limit, whichever is higher, as determined by multiple gated acquisition (MUGA)
scan or Trans-thoracic echocardiography (TTE).
Patients with uncontrolled hypertension defined as a Systolic Blood Pressure (SBP) >
140 mm Hg and/or Diastolic Blood Pressure (DBP) > 90 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 a history of congenital long QT syndrome, history of Torsade de Pointes
or patients with corrected QT (QTc) > 450 ms using Fridericia correction (QTcF) on
the screening ECG (as mean of triplicate ECGs).
8. Patients who have received thoracic radiotherapy to lung fields ≤ 4 weeks prior to starting
the study treatment or patients who have not recovered from radiotherapy-related
toxicities. For all other anatomic sites (including radiotherapy to thoracic vertebrae and
ribs), patients who have received radiotherapy ≤ 2 weeks prior to starting the study
treatment or patients who have not recovered from radiotherapy-related toxicities.
9. Patients who have had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic)
within 4 weeks (2 weeks for resection of brain metastases) prior to starting study treatment
or who have not recovered from side effects of such procedures. 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.
10. Patients participating in additional parallel investigational drug or medical device studies.
11. History or current evidence of retinal vein occlusion (RVO) or current risk factors for
RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or
hypercoagulability syndromes).
12. Patients with Gilbert’s syndrome or other heritable diseases of bile processing.
13. Any medical condition that would, in the investigator’s judgment, prevent the patient’s
participation in the clinical study due to safety concerns or compliance with clinical study
procedures. Any severe, acute, or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or study
treatment administration or that may interfere with the interpretation of study results and,
in the judgment of the investigator, would make the patient inappropriate for the study.
14. Prior therapies
Patients who have been treated with EGFR TKI in the adjuvant setting within 6
months, unless acquired EGFR T790M is present in a tumor or blood sample obtained
since the discontinuation of the EGFR TKI
Patients who have been treated with prior EGFR TKI targeting T790M (3rd
generation, e.g., osimertinib, CO-1686/rociletinib, ASP8273, HM61713/BI
1482694/olmutinib)
Patients who have been treated with systemic anti-neoplastic therapy within:
≤ 2 weeks for fluoropyrimidine monotherapy
≤6 weeks for nitrosoureas and mitomycin
≤4 weeks or ≤ 5 half-lives (whichever is shorter) for biological therapy (including
monoclonal antibodies) and continuous or intermittent small molecule
therapeutics or any other investigational agent
NOTE: Exceptions to the above may be made on a case by case basis, following
discussion and mutual agreement between investigator and Novartis.
Patients with unresolved toxicity greater than CTCAE grade 1 from prior anticancer
therapy or radiotherapy (excluding alopecia).
NOTE: Exceptions to this may be made on a case by case basis, following discussion
and mutual agreement between investigator and Novartis.
15. Patients who have out of range laboratory values defined as:
Absolute Neutrophil Count (ANC) <1.5 x 109
/L
Hemoglobin (Hgb) <9 g/dL
Platelets <100 x 109
/L
Total bilirubin > upper limit of normal (ULN) or >1.5 x ULN if liver metastases are
present at baseline.
Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.5 x
ULN for patients without hepatic metastasis.
AST and/or ALT >5 x ULN for patients with hepatic metastasis.
Alkaline phosphatase (ALP) >5 x ULN.
Fasting plasma glucose >175 mg/dL (>8.9 mmol/L).
Serum creatinine > 1.5 x ULN
Asymptomatic serum amylase > grade 2. Patients with grade 1 or grade 2 serum
amylase at the beginning of the study must be confirmed to have no signs and/or
symptoms suggesting pancreatitis or pancreatic injury (e.g., elevated P-amylase,
abnormal imaging findings of pancreas, etc.)
Serum lipase > ULN
16. Patients who have the following laboratory values outside of the laboratory normal limits
(treatment may be given during screening to correct values):
Potassium
Magnesium
Phosphorus
Total calcium (corrected for serum albumin)
17. Patients who are receiving treatment with the prohibited medications listed in Section
6.4.3 and Appendix 2, and which cannot be discontinued 7 days prior to the start of study
treatment and for the duration of the study.
18. Patients who have impairment of GI function or GI disease that may significantly alter the
absorption of study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting,
diarrhea, or malabsorption syndrome).
19. Patients who are unable or unwilling to swallow the oral drugs as per dosing schedule.
20. Patients who are receiving treatment with any enzyme-inducing anticonvulsant that cannot
be discontinued at least 1 week before first dose of study treatment, and for the duration of
the study. Patients on non-enzyme-inducing anticonvulsants are eligible.
21. Pregnant or nursing (lactating) women.
22. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during the study and for:
4 days after stopping EGF816 as a single agent
21 days after stopping EGF816 in combination with ribociclib, per prescribing
information for Kisqali®.
7 days after stopping EGF816 in combination with LXH254
7 days after stopping EGF816 in combination with INC280
2 weeks after stopping EGF816 in combination with gefitinib, per prescribing
information for IRESSA®.
4 months after stopping EGF816 in combination with trametinib, per prescribing
information for Mekinist®.
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, symptomthermal, postovulation methods)
and withdrawal are not acceptable methods of contraception.
Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total 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.
Use of oral, injected or implanted hormonal methods of contraception or placement of an
intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal
contraception that have comparable efficacy (failure rate <1%), for example hormone
vaginal ring or transdermal hormone contraception.
23. Sexually active males unless they use a condom during intercourse while taking the drug
during treatment, and for:
4 days after stopping EGF816 as a single agent
21 days after stopping EGF816 in combination with ribociclib
7 days after stopping EGF816 in combination with LXH254 or INC280
2 weeks after stopping EGF816 in combination with gefitinib
4 months after stopping EGF816 in combination with trametinib
Men should not father a child in these periods. A condom is required to be used by
vasectomized men as well as during intercourse with a male partner in order to prevent
delivery of the drug via semen.
Patients eligible for this study must not meet any of the following criteria:
For All patients (unless otherwise specified):
1. Patients with a history or presence of interstitial lung disease or interstitial pneumonitis,
including clinically significant radiation pneumonitis (i.e. affecting activities of daily
living or requiring therapeutic intervention).
2. Patients with unstable brain metastases. Patients with controlled brain metastases may
participate in the trial. They must complete any planned radiation therapy and/or
surgery >2 weeks prior to the first dose of study treatment and remain asymptomatic.
Patients on steroids must have been on a stable or decreasing low dose for 2 weeks prior to
initiating study treatment.
3. Patients with a history of another malignancy. Exception: patients who have been diseasefree for 3 years, or patients with a history of completely resected in-situ carcinoma of any
type, basal or squamous cell skin carcinoma, or stage IA melanoma that has been cured,
are eligible.
4. Patients who have undergone a bone marrow or solid organ transplant.
5. Patients with a known history of human immunodeficiency virus (HIV) seropositivity
(HIV testing is not mandatory).
6. Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use
at the time of study entry except for control of brain metastases, or in form of topical
applications, inhaled sprays, eye drops or local injections.
7. Patients with clinically significant, uncontrolled heart 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
Left ventricular ejection fraction (LVEF) < 50% or below the institutional standard
lower limit, whichever is higher, as determined by multiple gated acquisition (MUGA)
scan or Trans-thoracic echocardiography (TTE).
Patients with uncontrolled hypertension defined as a Systolic Blood Pressure (SBP) >
140 mm Hg and/or Diastolic Blood Pressure (DBP) > 90 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 a history of congenital long QT syndrome, history of Torsade de Pointes
or patients with corrected QT (QTc) > 450 ms using Fridericia correction (QTcF) on
the screening ECG (as mean of triplicate ECGs).
8. Patients who have received thoracic radiotherapy to lung fields ≤ 4 weeks prior to starting
the study treatment or patients who have not recovered from radiotherapy-related
toxicities. For all other anatomic sites (including radiotherapy to thoracic vertebrae and
ribs), patients who have received radiotherapy ≤ 2 weeks prior to starting the study
treatment or patients who have not recovered from radiotherapy-related toxicities.
9. Patients who have had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic)
within 4 weeks (2 weeks for resection of brain metastases) prior to starting study treatment
or who have not recovered from side effects of such procedures. 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.
10. Patients participating in additional parallel investigational drug or medical device studies.
11. History or current evidence of retinal vein occlusion (RVO) or current risk factors for
RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or
hypercoagulability syndromes).
12. Patients with Gilbert’s syndrome or other heritable diseases of bile processing.
13. Any medical condition that would, in the investigator’s judgment, prevent the patient’s
participation in the clinical study due to safety concerns or compliance with clinical study
procedures. Any severe, acute, or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or study
treatment administration or that may interfere with the interpretation of study results and,
in the judgment of the investigator, would make the patient inappropriate for the study.
14. Prior therapies
Patients who have been treated with EGFR TKI in the adjuvant setting within 6
months, unless acquired EGFR T790M is present in a tumor or blood sample obtained
since the discontinuation of the EGFR TKI
Patients who have been treated with prior EGFR TKI targeting T790M (3rd
generation, e.g., osimertinib, CO-1686/rociletinib, ASP8273, HM61713/BI
1482694/olmutinib)
Patients who have been treated with systemic anti-neoplastic therapy within:
≤ 2 weeks for fluoropyrimidine monotherapy
≤6 weeks for nitrosoureas and mitomycin
≤4 weeks or ≤ 5 half-lives (whichever is shorter) for biological therapy (including
monoclonal antibodies) and continuous or intermittent small molecule
therapeutics or any other investigational agent
NOTE: Exceptions to the above may be made on a case by case basis, following
discussion and mutual agreement between investigator and Novartis.
Patients with unresolved toxicity greater than CTCAE grade 1 from prior anticancer
therapy or radiotherapy (excluding alopecia).
NOTE: Exceptions to this may be made on a case by case basis, following discussion
and mutual agreement between investigator and Novartis.
15. Patients who have out of range laboratory values defined as:
Absolute Neutrophil Count (ANC) <1.5 x 109
/L
Hemoglobin (Hgb) <9 g/dL
Platelets <100 x 109
/L
Total bilirubin > upper limit of normal (ULN) or >1.5 x ULN if liver metastases are
present at baseline.
Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.5 x
ULN for patients without hepatic metastasis.
AST and/or ALT >5 x ULN for patients with hepatic metastasis.
Alkaline phosphatase (ALP) >5 x ULN.
Fasting plasma glucose >175 mg/dL (>8.9 mmol/L).
Serum creatinine > 1.5 x ULN
Asymptomatic serum amylase > grade 2. Patients with grade 1 or grade 2 serum
amylase at the beginning of the study must be confirmed to have no signs and/or
symptoms suggesting pancreatitis or pancreatic injury (e.g., elevated P-amylase,
abnormal imaging findings of pancreas, etc.)
Serum lipase > ULN
16. Patients who have the following laboratory values outside of the laboratory normal limits
(treatment may be given during screening to correct values):
Potassium
Magnesium
Phosphorus
Total calcium (corrected for serum albumin)
17. Patients who are receiving treatment with the prohibited medications listed in Section
6.4.3 and Appendix 2, and which cannot be discontinued 7 days prior to the start of study
treatment and for the duration of the study.
18. Patients who have impairment of GI function or GI disease that may significantly alter the
absorption of study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting,
diarrhea, or malabsorption syndrome).
19. Patients who are unable or unwilling to swallow the oral drugs as per dosing schedule.
20. Patients who are receiving treatment with any enzyme-inducing anticonvulsant that cannot
be discontinued at least 1 week before first dose of study treatment, and for the duration of
the study. Patients on non-enzyme-inducing anticonvulsants are eligible.
21. Pregnant or nursing (lactating) women.
22. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during the study and for:
4 days after stopping EGF816 as a single agent
21 days after stopping EGF816 in combination with ribociclib, per prescribing
information for Kisqali®.
7 days after stopping EGF816 in combination with LXH254
7 days after stopping EGF816 in combination with INC280
2 weeks after stopping EGF816 in combination with gefitinib, per prescribing
information for IRESSA®.
4 months after stopping EGF816 in combination with trametinib, per prescribing
information for Mekinist®.
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, symptomthermal, postovulation methods)
and withdrawal are not acceptable methods of contraception.
Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total 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.
Use of oral, injected or implanted hormonal methods of contraception or placement of an
intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal
contraception that have comparable efficacy (failure rate <1%), for example hormone
vaginal ring or transdermal hormone contraception.
23. Sexually active males unless they use a condom during intercourse while taking the drug
during treatment, and for:
4 days after stopping EGF816 as a single agent
21 days after stopping EGF816 in combination with ribociclib
7 days after stopping EGF816 in combination with LXH254 or INC280
2 weeks after stopping EGF816 in combination with gefitinib
4 months after stopping EGF816 in combination with trametinib
Men should not father a child in these periods. A condom is required to be used by
vasectomized men as well as during intercourse with a male partner in order to prevent
delivery of the drug via semen.
The Estimated Number of Participants
-
Taiwan
38 participants
-
Global
158 participants
