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Report for Clinical Trial NCT02580708

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase 1/2 Study of the Safety and Efficacy of Rociletinib When Administered in Combination With Trametinib in Patients With Activating EGFR Mutation-positive Advanced or Metastatic Non-small Lung Cancer (NSCLC)

The purpose of this study is to evaluate the safety and anti-tumor effect of rociletinib when administered in combination with trametinib.

NCT02580708 Non-small Cell Lung Cancer
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma

2 Interventions

Name: Rociletinib

Type: Drug
Group Labels: 1

Rociletinib and Trametinib

Name: Trametinib

Type: Drug
Group Labels: 1

Rociletinib and Trametinib


Primary Outcomes

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 months

Description: 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 months

Measure: Cmax of rociletinib and trametinib at steady state

Time: Cycle 2 Day 1 to Day 2

Measure: Tmax of rociletinib and trametinib at steady state

Time: Cycle 2 Day 1 to Day 2

Measure: AUC of rociletinib and trametinib at steady state

Time: Cycle 2 Day 1 to Day 2

Measure: Cmin of rociletinib and trametinib at steady state

Time: Cycle 2 Day 1 to Day 2

Measure: t1/2 of rociletinib at steady state

Time: Cycle 2 Day 1 to Day 2

Secondary Outcomes

Description: 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 months

Description: 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 months

Description: 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 months

Measure: Overall Survival (OS)

Time: Every 12 weeks until date of death, up to approximately 60 months

Measure: Longitudinal changes in blood based biomarkers (i.e. mutations in EGFR) in ctDNA

Time: Biomarker samples will be collected from each subject approximately every 3 weeks, up to approximately 24 months

Measure: Cmax of rociletinib metabolites at steady state

Time: Cycle 2 Day 1 to Day 2

Measure: Tmax of rociletinib metabolites at steady state

Time: Cycle 2 Day 1 to Day 2

Measure: AUC of rociletinib metabolites at steady state

Time: Cycle 2 Day 1 to Day 2

Measure: Cmin of rociletinib metabolites at steady state

Time: Cycle 2 Day 1 to Day 2

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There is one SNP

SNPs


1 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 ---

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 ---



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