Multicenter Study of Rociletinib Administered to Patients With Previously Treated Mutant EGFR Non-small Cell Lung Cancer

TIGER-2: A Phase 2, Open-label, Multicenter, Safety and Efficacy Study of Oral CO-1686 as 2nd Line EGFR-directed TKI in Patients With Mutant EGFR Non-small Cell Lung Cancer (NSCLC)

The purpose of this study is to evaluate the safety and anti-tumor effect of rociletinib. The trial is open-ended, which means patients will continue to take rociletinib until the study doctor determines it is no longer beneficial for them.

This is a Phase 2, single arm, open-label, dual cohort, multicenter study evaluating the safety and efficacy of rociletinib administered orally to patients with previously treated mutant EGFR NSCLC.

Patients will be enrolled into 2 cohorts. Cohort A will enroll approximately 125 eligible patients who are centrally confirmed T790M-positive. Cohort B will be a continuation of the study and will enroll up to approximately 100 eligible patients who will be either centrally confirmed T790M-positive or T790M-negative.

All patients (for Cohort A and B) should have experienced disease progression while on treatment with the first single-agent EGFR-directed TKI (EGFR-TKI) for advanced/metastatic NSCLC. One line of chemotherapy prior to the EGFR-TKI treatment is permissible.

The study (Cohorts A and B) will consist of a screening phase to establish study eligibility and document baseline measurements, an open-label treatment phase, in which the patient will receive rociletinib to ascertain safety and efficacy until disease progression as defined by RECIST Version 1.1, clinical tumor progression, or unacceptable toxicity as assessed by the investigator. For patients with clinical progression, radiographic assessment should be performed to document evidence of radiographic progression.

Inclusion Criteria

• Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC
• Documented evidence of a tumor with 1 or more EGFR mutations excluding exon 20 insertion
• Disease progression confirmed by radiologic assessment while receiving treatment with the first single agent EGFR-TKI
• EGFR TKI treatment discontinued less than or equal to 30 days prior to planned initiation of rociletinib
• The washout period for an EGFR inhibitor is a minimum of 3 days
• No intervening treatment between cessation of single agent EGFR TKI and planned initiation of rociletinib
• Previous treatment with less than or equal to 1 prior chemotherapy (excluding prior neo-adjuvant or adjuvant chemotherapy or chemoradiotherapy with curative intent)
• Any toxicity related to prior EGFR inhibitor treatment must have resolved to Grade 1 or less
• Central laboratory confirmation of the presence of the T790M mutation in tumor tissue in Cohort A and the presence or absence of the T790M mutation in tumor tissue in Cohort B. Centrally indeterminate, unknown or invalid specimens are not acceptable. Biopsy material obtained from either primary or metastatic tumor tissue and sent to the central laboratory must be within 60 prior to dosing study drug but following disease progression on the first EGFR TKI
• Measurable disease according to RECIST Version 1.1
• Life expectancy of at least 3 months
• ECOG performance status of 0 to 1
• Minimum Age 18 years (in certain territories, the minimum age requirement may be higher eg age 20 years in Japan and Taiwan)
• Adequate hematological and biological function, confirmed by defined laboratory values
• Written consent on an IRB/IEC-approved Informed Consent Form (ICF) prior to any study specific evaluation

Exclusion Criteria

• Documented evidence of an exon 20 insertion activating mutation in the EGFR gene
• Active second malignancy i.e. patient known to have potentially fatal cancer present for which he/she may be (but not necessarily) currently receiving treatment
• Patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enrol in the trial provided all chemotherapy was completed greater than 6 months prior and/or bone marrow transplant greater than 2 years prior
• Known pre-existing interstitial lung disease
• Cohort A only: Patients with leptomeningeal carcinomatosis are excluded. Other central nervous system (CNS) metastases are only permitted if treated, asymptomatic, and stable (not requiring steroid for at least 4 weeks prior to the start of study treatment). Cohort B only: Patients with CNS metastases or leptomeningeal carcinomatosis are excluded.
• Treatment with prohibited medications less than or equal to 14 days prior to treatment with rociletinib
• Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication before starting rociletinib
• Prior treatment with rociletinib, or other drugs that target T790M positive mutant EGFR with sparing of wild type EGFR
• Any of the following cardiac abnormalities or history
• Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTCF) greater than 450 msec
• Inability to measure QT interval on ECG
• Personal or family history of long QT syndrome
• Implantable pacemaker or implantable cardioverter defibrillator
• Resting bradycardia less than 55 beats/min
• Non-study related surgical procedures less than or equal to 7 days prior to administration of rociletinib. In all cases, the patient must be sufficiently recovered and stable before treatment administration
• Females who are pregnant or breastfeeding
• Refusal to use adequate contraception for fertile patients (females and males) while on treatment and for 12 weeks after the last dose of rociletinib
• Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study
• Any other reason the investigator considers the patient should not participate in the study