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

Inclusion Criteria: All patients must meet all of the following inclusion criteria: 1. Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with radiological progression on the most recent therapy received 2. Documented evidence of a tumor with 1 or more EGFR activating mutations excluding exon 20 insertion 3. Disease progression confirmed by radiological assessment while receiving treatment with single agent EGFR-TKI (e.g., erlotinib, gefitinib, afatinib, or dacomitinib) or EGFR-TKI in combination with other targeted therapy (e.g. bevacizumab, immunotherapy) 4. Multiple lines of prior treatment are permitted and there is no specified order of treatment, but in the course of their treatment history, patients must have received and have radiologically documented disease progression following: At least 1 line of prior treatment with a single-agent EGFR-TKI (e.g., erlotinib, gefitinib, afatinib, or dacomitinib) If EGFR-TKI is a component of the most recent treatment line, the washout period for the EGFR-TKI is a minimum of 3 days before the start of study drug treatment AND A platinum-containing doublet chemotherapy (either progressed during therapy or completed at least 4 cycles without progression with subsequent progression after a treatment-free interval or after a maintenance treatment). If cytotoxic chemotherapy is a component of the most recent treatment line, treatment with chemotherapy should have been completed at least 14 days prior to start of study treatment. When an EGFR-TKI is given in combination with platinum-containing doublet chemotherapy, treatment with the EGFR-TKI may continue until at least 3 days before start of treatment. 5. Have undergone a biopsy of either primary or metastatic tumor tissue within 60 days prior to start of treatment and have tissue sent to the central laboratory prior to randomization 6. Measureable disease according to RECIST Version 1.1 7. Life expectancy of at least 3 months 8. ECOG performance status of 0 to 1 9. Age ≥ 18 years (in certain territories, the minimum age requirement may be higher e.g., age ≥ 20 years in Japan and Taiwan, age ≥ 21 years in Singapore) 10. Patients should have recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade ≤ 1 from any significant chemotherapy-related toxicities 11. Adequate hematological and biological function 12. Written consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF before any study specific evaluation 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