TIGER-1: Safety and Efficacy Study of Rociletinib (CO-1686) or Erlotinib in Patients With EGFR-mutant/Metastatic NSCLC Who Have Not Had Any Previous EGFR Directed Therapy

This is a randomized, Phase 2/3 study of rociletinib versus erlotinib as a first-line
treatment for patients with EGFR-mutant advanced/metastatic NSCLC whose tumors have
EGFR-activating mutations. The study will consist of Phase 2 and Phase 3 parts which will
use the same enrollment criteria and treatment assignment principles. Patients will be
randomized 1:1 to erlotinib or rociletinib. The Phase 2 part is an open-label study. In the
Phase 3 part, the sponsor will be blinded to the efficacy and safety results. The study will
consist of a screening phase to establish study eligibility (including tumor genotype) and
document baseline measurements, a treatment phase, in which patients will receive either
rociletinib BID or erlotinib QD to ascertain safety and efficacy until protocol-defined
disease progression, and a follow-up phase, to monitor survival status and subsequent NCSLC
cancer therapy. In the Phase 2 part only, patients initially randomized to erlotinib may be
eligible to participate in an optional crossover phase to receive rociletinib if they
demonstrate the T790M resistance mutation after radiographic progression on erlotinib
treatment among other eligibility requirements. Patients eligible for this study must have
EGFR-mutated NSCLC who have not been treated with an EGFR-directed therapy.Treatment with
rociletinib or erlotinib is continuous. Each 28 day period of treatment will represent one
cycle, with dosing initiated on Cycle 1 Day 1 (C1 D1).

Inclusion Criteria:

1. Histologically or cytologically confirmed metastatic or unresectable locally
advanced/metastatic NSCLC

2. Documented evidence of a tumor with activating EGFR mutations by local testing.
Patients with exon 20 insertions are not eligible with the exception of patients with
documented evidence of the exon 20 insertion A763_Y764insFQEA in the EGFR gene

3. Have undergone a biopsy or surgical resection of either primary or metastatic tumor
tissue within 60 days of the first day of study treatment, C1D1, and have tissue
available to send to sponsor laboratories or are able to undergo a biopsy during
screening and provide tissue to sponsor laboratories

4. Measureable disease according to RECIST Version 1.1

5. Life expectancy of at least 3 months

6. ECOG performance status of 0 to 1

7. Minimum age 18 years (in certain territories, the minimum age requirement may be
higher (e.g. 20 years in Japan and Taiwan)

8. Adequate hematological and biological function, confirmed by defined laboratory
values

9. Written consent on an IRB/IEC-approved Informed Consent Form (ICF) prior to any
study-specific evaluation

Exclusion Criteria:

1. Documented evidence of an exon 20 insertion activating mutation other than
A763_Y764insFQEA in the EGFR gene

2. Prior treatment with cytotoxic chemotherapy for advanced NSCLC; neoadjuvant/adjuvant
chemotherapy is permitted if at least 6 months has elapsed between the end of
chemotherapy and randomization

3. 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

4. Patients with a history of malignancy that has been completely treated, and currently
with no evidence of that cancer, are permitted to enroll in the trial provided all
chemotherapy was completed > 6 months prior and/or bone marrow transplant > 2 years
prior to first day of study treatment

5. Known pre-existing interstitial lung disease

6. Brain metastases

7. Treatment with prohibited medications less than or equal to 14 days prior to first
day of study treatment

8. Patients who are currently receiving treatment with any medications that have the
potential to prolong the QT interval if that treatment cannot be either discontinued
or switched to a different medication prior to administration of study drug

9. Prior treatment with EGFR TKIs (e.g. erlotinib, gefitinib, neratinib, afatinib,
AZD9291, or dacomitinib), rociletinib or other drugs that target mutant EGFR

10. Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's
method (QTCF) > 450 ms

11. Inability to measure QT interval on ECG

12. Personal or family history of long QT syndrome

13. Implantable pacemaker or implantable cardioverter defibrillator

14. Resting bradycardia < 55 beats/min

15. Non-study related surgical procedures less than or equal to 7 days prior to
administration of study drug. In all cases, the patient must be sufficiently
recovered and stable before treatment administration.

16. Females who are pregnant or breastfeeding

17. Refusal to use adequate contraception for fertile patients (females and males) for 12
weeks after the last dose of rociletinib and 2 weeks after the last dose of erlotinib

18. Presence of any serious or unstable concomitant systemic disorder incompatible with
the clinical study

19. Any other reason the investigator considers the patient should not participate in the
study