The purpose of this study is to evaluate the safety and anti-tumor effect of rociletinib when administered in combination with trametinib.
Name: Rociletinib
Type: DrugRociletinib and Trametinib
Name: Trametinib
Type: DrugRociletinib and Trametinib
Description: Treatment emergent adverse events (AEs), laboratory abnormalities and ECG abnormalities in EGFR-mutant NSCLC patients given oral rociletinib in combination with oral trametinib; defining in Phase 1 the recommended combination dose for further evaluation in Phase 2
Measure: Incidence of treatment-emergent adverse events Time: Continuously, up to approximately 24 monthsDescription: ORR according to RECIST Version 1.1 as determined by Investigator assessment
Measure: Objective Response Rate (ORR) Time: Every 6 weeks until disease progression, up to approximately 24 monthsDescription: DR according to RECIST Version 1.1 as determined by Investigator assessment
Measure: Duration of Response (DR) According to RECIST Version 1.1 Time: Every 6 weeks until disease progression, up to approximately 24 monthsDescription: DCR according to RECIST Version 1.1 as determined by Investigator assessment
Measure: Disease Control Rate (DCR) According to RECIST Version 1.1 Time: Every 6 weeks until disease progression, up to approximately 24 monthsDescription: PFS according to RECIST Version 1.1 as determined by Investigator assessment
Measure: Progression Free Survival (PFS) According to RECIST Version 1.1 Time: Every 6 weeks until disease progression, up to approximately 24 monthsSingle Group Assignment
There is one SNP
Inclusion Criteria: - Written informed consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF before any study-specific evaluation - Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with EGFR activating mutation (excluding exon 20 insertion); measurable disease per RECIST 1.1 - Prior treatment with an EGFR TKI; in Phase 2, prior treatment with a T790M-directed EGFR TKI for patients in Group B. Previous chemotherapy is allowed; in Phase 2, immediate prior therapy must be EGFR TKI - Patient willingness to undergo tumor biopsy at baseline and on treatment (optional for Phase 1; mandatory for Phase 2) - Eastern Cooperative Oncology Group (ECOG) performance status 0-1; life expectancy at least 3 months - Adequate hematological and biological function; LVEF ≥50% Exclusion Criteria: - Documented evidence in tumor of exon 20 insertion, small cell transformation, or MET amplification - Leptomeningeal carcinomatosis or other untreated or symptomatic CNS metastases (asymptomatic CNS metastases allowed if clinically stable without requirement for steroids within 2 weeks) - Known preexisting interstitial lung disease or pneumonitis - Concurrent use of QT-prolonging medication - Uncontrolled diabetes (HA1C > 10%) despite optional therapy - Cardiac abnormalities: - Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTcF) >450 ms - Inability to measure QT interval on ECG - Personal or family history of long QT syndrome - Implantable pacemaker or implantable cardioverter defibrillator - Resting bradycardia < 55 beats/min - Inability to swallow oral study treatment or any gastrointestinal disease or condition that would preclude adequate absorption of study treatment - Presence of serious or unstable concomitant systemic disorder incompatible with the clinical study (eg, substance abuse; uncontrolled intercurrent illness including active infection; arterial thrombosis; unstable respiratory, hepatic, renal or cardiac disease; and other active malignancy) - Pregnant or breastfeeding females and male or female patients who refuse to use adequate contraception during the study and for 16 weeks after the last dose of study treatment - Any contraindication, allergy, or hypersensitivity to rociletinib, trametinib, or excipients Inclusion Criteria: - Written informed consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF before any study-specific evaluation - Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with EGFR activating mutation (excluding exon 20 insertion); measurable disease per RECIST 1.1 - Prior treatment with an EGFR TKI; in Phase 2, prior treatment with a T790M-directed EGFR TKI for patients in Group B. Previous chemotherapy is allowed; in Phase 2, immediate prior therapy must be EGFR TKI - Patient willingness to undergo tumor biopsy at baseline and on treatment (optional for Phase 1; mandatory for Phase 2) - Eastern Cooperative Oncology Group (ECOG) performance status 0-1; life expectancy at least 3 months - Adequate hematological and biological function; LVEF ≥50% Exclusion Criteria: - Documented evidence in tumor of exon 20 insertion, small cell transformation, or MET amplification - Leptomeningeal carcinomatosis or other untreated or symptomatic CNS metastases (asymptomatic CNS metastases allowed if clinically stable without requirement for steroids within 2 weeks) - Known preexisting interstitial lung disease or pneumonitis - Concurrent use of QT-prolonging medication - Uncontrolled diabetes (HA1C > 10%) despite optional therapy - Cardiac abnormalities: - Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTcF) >450 ms - Inability to measure QT interval on ECG - Personal or family history of long QT syndrome - Implantable pacemaker or implantable cardioverter defibrillator - Resting bradycardia < 55 beats/min - Inability to swallow oral study treatment or any gastrointestinal disease or condition that would preclude adequate absorption of study treatment - Presence of serious or unstable concomitant systemic disorder incompatible with the clinical study (eg, substance abuse; uncontrolled intercurrent illness including active infection; arterial thrombosis; unstable respiratory, hepatic, renal or cardiac disease; and other active malignancy) - Pregnant or breastfeeding females and male or female patients who refuse to use adequate contraception during the study and for 16 weeks after the last dose of study treatment - Any contraindication, allergy, or hypersensitivity to rociletinib, trametinib, or excipients Non-small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung This is a Phase 1/2, open-label, non randomized, multicenter study evaluating the safety and efficacy of rociletinib administered in combination with trametinib. --- T790M ---
Inclusion Criteria: - Written informed consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF before any study-specific evaluation - Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with EGFR activating mutation (excluding exon 20 insertion); measurable disease per RECIST 1.1 - Prior treatment with an EGFR TKI; in Phase 2, prior treatment with a T790M-directed EGFR TKI for patients in Group B. Previous chemotherapy is allowed; in Phase 2, immediate prior therapy must be EGFR TKI - Patient willingness to undergo tumor biopsy at baseline and on treatment (optional for Phase 1; mandatory for Phase 2) - Eastern Cooperative Oncology Group (ECOG) performance status 0-1; life expectancy at least 3 months - Adequate hematological and biological function; LVEF ≥50% Exclusion Criteria: - Documented evidence in tumor of exon 20 insertion, small cell transformation, or MET amplification - Leptomeningeal carcinomatosis or other untreated or symptomatic CNS metastases (asymptomatic CNS metastases allowed if clinically stable without requirement for steroids within 2 weeks) - Known preexisting interstitial lung disease or pneumonitis - Concurrent use of QT-prolonging medication - Uncontrolled diabetes (HA1C > 10%) despite optional therapy - Cardiac abnormalities: - Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTcF) >450 ms - Inability to measure QT interval on ECG - Personal or family history of long QT syndrome - Implantable pacemaker or implantable cardioverter defibrillator - Resting bradycardia < 55 beats/min - Inability to swallow oral study treatment or any gastrointestinal disease or condition that would preclude adequate absorption of study treatment - Presence of serious or unstable concomitant systemic disorder incompatible with the clinical study (eg, substance abuse; uncontrolled intercurrent illness including active infection; arterial thrombosis; unstable respiratory, hepatic, renal or cardiac disease; and other active malignancy) - Pregnant or breastfeeding females and male or female patients who refuse to use adequate contraception during the study and for 16 weeks after the last dose of study treatment - Any contraindication, allergy, or hypersensitivity to rociletinib, trametinib, or excipients Inclusion Criteria: - Written informed consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF before any study-specific evaluation - Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with EGFR activating mutation (excluding exon 20 insertion); measurable disease per RECIST 1.1 - Prior treatment with an EGFR TKI; in Phase 2, prior treatment with a T790M-directed EGFR TKI for patients in Group B. Previous chemotherapy is allowed; in Phase 2, immediate prior therapy must be EGFR TKI - Patient willingness to undergo tumor biopsy at baseline and on treatment (optional for Phase 1; mandatory for Phase 2) - Eastern Cooperative Oncology Group (ECOG) performance status 0-1; life expectancy at least 3 months - Adequate hematological and biological function; LVEF ≥50% Exclusion Criteria: - Documented evidence in tumor of exon 20 insertion, small cell transformation, or MET amplification - Leptomeningeal carcinomatosis or other untreated or symptomatic CNS metastases (asymptomatic CNS metastases allowed if clinically stable without requirement for steroids within 2 weeks) - Known preexisting interstitial lung disease or pneumonitis - Concurrent use of QT-prolonging medication - Uncontrolled diabetes (HA1C > 10%) despite optional therapy - Cardiac abnormalities: - Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTcF) >450 ms - Inability to measure QT interval on ECG - Personal or family history of long QT syndrome - Implantable pacemaker or implantable cardioverter defibrillator - Resting bradycardia < 55 beats/min - Inability to swallow oral study treatment or any gastrointestinal disease or condition that would preclude adequate absorption of study treatment - Presence of serious or unstable concomitant systemic disorder incompatible with the clinical study (eg, substance abuse; uncontrolled intercurrent illness including active infection; arterial thrombosis; unstable respiratory, hepatic, renal or cardiac disease; and other active malignancy) - Pregnant or breastfeeding females and male or female patients who refuse to use adequate contraception during the study and for 16 weeks after the last dose of study treatment - Any contraindication, allergy, or hypersensitivity to rociletinib, trametinib, or excipients Non-small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung This is a Phase 1/2, open-label, non randomized, multicenter study evaluating the safety and efficacy of rociletinib administered in combination with trametinib. --- T790M --- --- T790M ---