Phase 1/2 Study of the Safety and Efficacy of Rociletinib in Combination With Trametinib in Patients With mEGFR-positive Advanced or Metastatic Non-small Cell Lung Cancer

This is a Phase 1/2, open-label, non randomized, multicenter study evaluating the safety and
efficacy of rociletinib administered in combination with trametinib.

This study will be conducted in 2 phases:

Phase 1: This will be the dose escalation phase of the study. Phase 1 will determine the MAD
or MTD and RP2D of the combination of rociletinib and trametinib, and evaluate its safety and
tolerability and PK profile in EGFRm NSCLC patients who have failed at least one prior EGFR
TKI.

Phase 2: This will be the dose expansion phase. Phase 2 will evaluate the preliminary
efficacy and pharmacodynamics of the combination of rociletinib and trametinib at the RP2D in
two subsets of EGFRm NSCLC patients.

Inclusion Criteria:

- Written informed consent on an Institutional Review Board (IRB)/Independent Ethics
Committee (IEC)-approved ICF before any study-specific evaluation

- Histologically or cytologically confirmed metastatic or unresectable locally advanced
NSCLC with EGFR activating mutation (excluding exon 20 insertion); measurable disease
per RECIST 1.1

- Prior treatment with an EGFR TKI; in Phase 2, prior treatment with a T790M-directed
EGFR TKI for patients in Group B. Previous chemotherapy is allowed; in Phase 2,
immediate prior therapy must be EGFR TKI

- Patient willingness to undergo tumor biopsy at baseline and on treatment (optional for
Phase 1; mandatory for Phase 2)

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1; life expectancy at
least 3 months

- Adequate hematological and biological function; LVEF ≥50%

Exclusion Criteria:

- Documented evidence in tumor of exon 20 insertion, small cell transformation, or MET
amplification

- Leptomeningeal carcinomatosis or other untreated or symptomatic CNS metastases
(asymptomatic CNS metastases allowed if clinically stable without requirement for
steroids within 2 weeks)

- Known preexisting interstitial lung disease or pneumonitis

- Concurrent use of QT-prolonging medication

- Uncontrolled diabetes (HA1C > 10%) despite optional therapy

- Cardiac abnormalities:

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

- Inability to measure QT interval on ECG

- Personal or family history of long QT syndrome

- Implantable pacemaker or implantable cardioverter defibrillator

- Resting bradycardia < 55 beats/min

- Inability to swallow oral study treatment or any gastrointestinal disease or condition
that would preclude adequate absorption of study treatment

- Presence of serious or unstable concomitant systemic disorder incompatible with the
clinical study (eg, substance abuse; uncontrolled intercurrent illness including
active infection; arterial thrombosis; unstable respiratory, hepatic, renal or cardiac
disease; and other active malignancy)

- Pregnant or breastfeeding females and male or female patients who refuse to use
adequate contraception during the study and for 16 weeks after the last dose of study
treatment

- Any contraindication, allergy, or hypersensitivity to rociletinib, trametinib, or
excipients