TIGER-3: Open Label, Multicenter Study of Rociletinib (CO-1686) Mono Therapy Versus Single-agent Cytotoxic Chemotherapy in Patients With Mutant EGFR NSCLC Who Have Failed at Least One Previous EGFR-Directed TKI and Platinum-doublet Chemotherapy

Exclusion Criteria

• •Any of the following criteria will exclude patients from study participation:
• •1. Any other malignancy associated with a high mortality risk within the next 5 years and for which the patients 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 enroll in the trial provided all chemotherapy was completed \> 6 months prior and/or bone marrow transplant \> 2 years prior
• •2. Known pre-existing interstitial lung disease
• •3. Tumor small cell transformation by local assessment, irrespective of presence of T790M+ component
• •4. Patients with leptomeningeal carcinomatosis are excluded. Other central nervous system (CNS) metastases are only permitted if treated, asymptomatic, and stable (not requiring steroids for at least 2 weeks prior to randomization and the patient is neurologically stable i.e. free from new symptoms of brain metastases)
• •5. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and that treatment cannot be either discontinued or switched to a different medication (known to have no effect on QT) before starting protocol-specified treatment (see http://crediblemeds.org/ for a list of QT-prolonging medications)
• •6. Prior treatment with rociletinib, or other drugs that target T790M+ mutant EGFR with sparing of WT-EGFR including but not limited to osimertinib, HM61713, and TAS-121
• •7. Any contraindications for therapy with pemetrexed, paclitaxel, gemcitabine or docetaxel unless a contraindication with respect to one of these drugs will not affect the use of any of the others as a comparator to rociletinib
• •8. Any of the following cardiac abnormalities or history:
• •1. Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTCF) \> 450 msec
• •2. Inability to measure QT interval on ECG
• •3. Personal or family history of long QT syndrome
• •4. Implantable pacemaker or implantable cardioverter defibrillator
• •5. Resting bradycardia \< 55 beats/min
• •9. Non-study related surgical procedures ≤ 7 days prior to randomization. In all cases, the patient must be sufficiently recovered and stable before treatment administration
• •10. Females who are pregnant or breastfeeding
• •11. Refusal to use adequate contraception for fertile patients (females and males) while on treatment and for 6 months after the last dose of study treatment (rociletinib and chemotherapy irrespective of single cytotoxic agent used)
• •12. Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, uncontrolled intercurrent illness including uncontrolled diabetes, active infection, arterial thrombosis, and symptomatic pulmonary embolism)
• •13. Any other reason the investigator considers the patient should not participate in the study
• •14. Treatment with live vaccines initiated less than 4 weeks prior to randomization