Study to Evaluate Safety, Pharmacokinetics, and Efficacy of Rociletinib (CO-1686) in Previously Treated Mutant Epidermal Growth Factor Receptor (EGFR) in Non-Small Cell Lung Cancer (NSCLC) Patients

Lung cancer remains the most common cancer worldwide with non-small cell lung cancer
accounting for 85% of cases. Cytotoxic chemotherapy has been the mainstay of patients with
NSCLC; however, survival rates remain low and toxicity is significant. Molecularly targeted
therapies have proven to be superior to chemotherapy for NSCLC patients whose tumors have
mutations in EGFR. Recent studies have established tyrosine kinase inhibitors (TKIs) as the
gold standard for treating EGFR-mutation-positive NCSLC. However, patients on TKIs eventually
progress, and in approximately 50% of cases, progression is due to development of an
additional mutation called T790M. There are currently no approved therapies for patients who
progress on TKIs. Rociletinib may provide an effective therapy for a patient population with
few alternative treatment options. Nonclinical data demonstrate that rociletinib inhibits
T790M. It is anticipated that rociletinib may promote cell death in tumor cells with the
T790M mutation, thus providing possible therapeutic benefit in patients who have developed
T790M-mediated resistance to first generation TKIs.

This is a two-part, open-label study of oral rociletinib administered daily in previously
treated NSCLC patients who have documented evidence of an activating mutation in the EGFR
gene and have failed treatment with an EGFR inhibitor such as erlotinib, gefitinib or
afatinib.

This study will include 2 parts:

Phase 1 (completed enrolment): Dose-escalation Period with 21-day cycles; optional Treatment
Extension Period starting on Day 22

Phase 2 (currently enrolling): Evaluation of activity and safety in patients with the T790M
EGFR mutation who have:

Cohort A - Progressed on EGFR directed therapy (irrespective of the number and order of
previous lines of NSCLC therapy) or Cohort B - Progression on the first single agent EGFR
directed therapy received and also had no more than one previous line of chemotherapy

Inclusion Criteria -

All patients must meet the following inclusion criteria:

1. Metastatic or unresectable locally advanced NSCLC

2. Evidence of a tumor with one or more EGFR mutations excluding exon 20 insertion

3. Biopsy of either primary or metastatic tumor tissue within 60 days of dosing

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

5. Minimum age of 18 years

6. Adequate hematological and biological function

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

Phase 2 Cohorts must also meet the following inclusion criteria:

- Disease progression confirmed by radiologic assessment while on treatment with EGFR-
TKI Or

- Disease progression confirmed by radiologic assessment while on treatment with the
first single agent EGFR TKI and

- Documented evidence of T790M mutation in EGFR following disease progression on the
first single agent EGFR TKI.

- Measureable disease according to RECIST Version 1.1

Exclusion Criteria -

Any of the following criteria will exclude patients from study participation:

1. Documented evidence of an Exon 20 insertion activating mutation in the EGFR gene

2. Active second malignancy

3. Known pre-existing interstitial lung disease

4. Patients with Leptomeningeal carcinomatosis are excluded. Other CNS metastases are
only permitted if treated, asymptomatic and stable (not requiring steroids for at
least 4 weeks prior to start of study treatment).

5. Treatment with prohibited medications less than or equal to 14 days prior to treatment
with rociletinib

6. 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

7. Prior treatment with rociletinib or other drugs that target T790M positive mutant EGFR
with sparing of wild type EGFR

8. Certain cardiac abnormalities or history

9. Non-study related surgical procedures less than or equal to 7 days prior to
administration of rociletinib

10. Females who are pregnant or breastfeeding

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

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

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