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

A Phase 1/2, Open-Label, Safety, Pharmacokinetic and Preliminary Efficacy Study of Oral Rociletinib in Patients With Previously Treated Mutant EGFR Non-Small Cell Lung Cancer (NSCLC)

Status

Terminated

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01526928

Enrollment

612

Registered

2012-02-06

Start date

2012-03-27

Completion date

2018-08-27

Last updated

2020-08-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Locally Advanced or Metastatic Non Small Cell Lung Cancer

Keywords

cancer, metastatic, locally advanced, lung, non-small cell lung cancer, NSCLC, epidermal growth factor receptor, EGFR, T790M, CO-1686, unresectable, recurrent, EGFR-directed therapy, irreversible EGFR inhibitor, TIGER, Rociletinib

Brief summary

Rociletinib is a novel, potent, small molecule irreversible tyrosine kinase inhibitor (TKI) that selectively targets mutant forms of the epidermal growth factor receptor (EGFR) while sparing wild-type (WT) EGFR. The purpose of the study is to evaluate the pharmacokinetic (PK) and safety profile of oral rociletinib; to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of oral rociletinib; to assess the safety and efficacy of rociletinib in previously treated NSCLC patients known to have the T790M EGFR mutation.

Detailed description

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: Dose-escalation Period with 21-day cycles; optional Treatment Extension Period starting on Day 22 Phase 2: 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 or Cohort C - Patients with discordance between local (T790M positive) and central (T790M negative) T790M results, or had no central test result due to inadequacy of the tissue specimen and known to be T790M positive by local test

Interventions

DRUGRociletinib

Phase 1: Rociletinib \<900 mg BID FB will be administered in escalating dosages in a period of 21-day cycles

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Percentage of T790M Positive Patients With Confirmed Response Per Investigator	Cycle 1 Day 1 to End of Treatment, up to approximately 42 months	Percentage of patients with a T790M mutation (determined by central lab) with a best overall confirmed response of partial response (PR) or complete response (CR) recorded from the start of the treatment until disease progression or recurrence. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR),at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.
Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment	Cycle 1 Day 1 to End of Treatment, up to approximately 36 months	Duration of Response in patients with a T790M mutation (determined by central lab) with confirmed response per investigator. The DOR for complete response (CR) and partial response (PR) was measured from the date that any of these best responses is first recorded until the first date that progressive disease (PD) is objectively documented. For patients who continue treatment post-progression, the first date of progression was used for the analysis.
Dose Limiting Toxicity (DLT) Incidence	Cycle 1 Day 1 to Cycle 1 Day 21	The number of Phase 1 patients who experienced dose limiting toxicities after one cycle (21 days) of study drug.

Secondary

Measure	Time frame	Description
PK Profile of Rociletinib - Tmax	Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days	Tmax = time to maximum concentration following administration of rociletinib
PK Profile of Rociletinib - AUC 0-24	Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days	AUC 0-24 = area under the curve from 0 to 24 hours
PK Profile of Rociletinib - T 1/2	Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days	T 1/2 = elimination half-life following administration of rociletinib
Food Effect on PK of Rociletinib - Cmax	Day -7 prior to Cycle 1 Day 1, or approximately 7 days	Cmax = maximum concentration following administration of rociletinib. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
Food Effect on PK of Rociletinib - Tmax	Day -7 prior to Cycle 1 Day 1, or approximately 7 days	Tmax = time to maximum concentration following administration of rociletinib. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
Overall Survival (OS) Determined by Investigator Assessment	Cycle 1 Day 1 to date of death, assessed up to 42 months	Overall survival was calculated as 1+ the number of days from the first dose of study drug to death due to any cause. Patients without a documented date of death were censored on the date the patient was last known to be alive.
Food Effect on PK of Rociletinib - C24	Day -7 prior to Cycle 1 Day 1, or approximately 7 days	C24 = rociletinib plasma concentration at 24 hours post the morning dose. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
Food Effect on PK of Rociletinib - T 1/2	Day -7 prior to Cycle 1 Day 1, or approximately 7 days	T 1/2 = elimination half-life following administration of rociletinib. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
QTcF Values Post Baseline by Daily Dose	Screening to End of Treatment, up to approximately 42 months	Frequency of QT interval prolongation by daily dose (corrected using Fridericia's method, QTcF). To evaluate the effects of rociletinib on the QT (interval from Q wave to T wave)/QTc (interval corrected for heart rate) interval, all patients underwent serial ECG monitoring at Baseline, on Cycle 1 Day 1, Cycle 1 Day 15, on Day 1 of all subsequent cycles, at the EOT Visit, and as clinically indicated. Worst post-baseline QTcF value was used to categorize each patient.
QTcF Value Change From Baseline	Screening to End of Treatment, up to approximately 42 months	QTcF value change from baseline by daily dose (corrected using Fridericia's method, QTcF). To evaluate the effects of rociletinib on the QT (interval from Q wave to T wave)/QTc (interval corrected for heart rate) interval, all patients underwent serial ECG monitoring at Baseline, on Cycle 1 Day 1, Cycle 1 Day 15, on Day 1 of all subsequent cycles, at the EOT Visit, and as clinically indicated. Worst post-baseline QTcF value was used to categorize each patient.
Objective Response Rate (ORR), Duration of Response (DOR) and Progression-Free Survival (PFS) Per RECIST Version 1.1 as Determined by IRR	Cycle 1 Day 1 to End of Treatment / End of Follow-up	Objective response rate (ORR), duration of response (DOR) and progression-free survival (PFS) per RECIST Version 1.1 as determined by independent radiology review (IRR)
Food Effect on PK of Rociletinib - AUC 0-24	Day -7 prior to Cycle 1 Day 1, or approximately 7 days	AUC 0-24 = area under the curve from 0 to 24 hours. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.
Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)	Cycle 1 Day 1 to End of Treatment, up to approximately 42 months	Progression-free survival was calculated as the number of days from the date of the first dose of study drug to the date of disease progression or death due to any cause + 1. Patients without a documented event of disease progression were censored on the date of their last adequate tumor assessment (i.e., radiologic assessment) or date of first dose of study drug if no tumor assessments have been performed. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
PK Profile of Rociletinib - Cmax	Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days	Cmax = maximum concentration following administration of rociletinib

Countries

Australia, France, Poland, United States

Participant flow

Recruitment details

There were 612 patients who received rociletinib-111 enrolled in Phase 1 and 501 enrolled in Phase 2. The Phase 1 component of the study was conducted at 8 study sites in the US, Australia, and France. Phase 2 was conducted at 49 study sites in the US, France, Poland, and Australia.

Participants by arm

Arm	Count
Rociletinib <900 mg BID FB Capsules Rociletinib free base (FB) dose \<900 mg twice a day (BID).	38
Rociletinib 900 mg BID FB Capsules Rociletinib free base (FB) dose 900 mg twice a day (BID).	19
Rociletinib 500 mg BID HBr Tablets Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID).	209
Rociletinib 625 mg BID HBr Tablets Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID).	245
Rociletinib 750 mg BID HBr Tablets Rociletinib hydrobromide (HBr) dose 750 mg twice a day (BID).	95
Rociletinib 1000 mg BID HBr Tablets Rociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID).	6
Total	612

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005
Overall Study	Adverse Event	2	1	29	40	13	2
Overall Study	Death	0	0	3	0	0	0
Overall Study	Lost to Follow-up	0	0	0	1	0	0
Overall Study	Missing	0	0	1	0	2	0
Overall Study	Other Reason	0	1	11	4	1	0
Overall Study	Physician Decision	0	0	2	5	0	0
Overall Study	Progressive Disease	35	17	150	182	76	4
Overall Study	Protocol Deviation	0	0	0	2	0	0
Overall Study	Withdrawal by Subject	1	0	13	11	3	0

Baseline characteristics

Characteristic	Total	Rociletinib 1000 mg BID HBr Tablets	Rociletinib 750 mg BID HBr Tablets	Rociletinib 625 mg BID HBr Tablets	Rociletinib 500 mg BID HBr Tablets	Rociletinib 900 mg BID FB Capsules	Rociletinib <900 mg BID FB Capsules
Age, Continuous	62.5 years STANDARD_DEVIATION 11.29	65.2 years STANDARD_DEVIATION 5.53	61.5 years STANDARD_DEVIATION 11.82	62.5 years STANDARD_DEVIATION 11.14	63.6 years STANDARD_DEVIATION 11.45	58.9 years STANDARD_DEVIATION 8.37	60.1 years STANDARD_DEVIATION 11.54
Ethnicity (NIH/OMB) Hispanic or Latino	25 Participants	0 Participants	2 Participants	14 Participants	5 Participants	2 Participants	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	495 Participants	6 Participants	90 Participants	184 Participants	170 Participants	15 Participants	30 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	92 Participants	0 Participants	3 Participants	47 Participants	34 Participants	2 Participants	6 Participants
History of CNS Metastases	267 Participants	3 Participants	44 Participants	107 Participants	86 Participants	7 Participants	20 Participants
Number of Previous Therapies	2.9 Therapies STANDARD_DEVIATION 1.88	3.8 Therapies STANDARD_DEVIATION 2.04	2.9 Therapies STANDARD_DEVIATION 2.11	2.8 Therapies STANDARD_DEVIATION 1.91	2.6 Therapies STANDARD_DEVIATION 1.74	3.7 Therapies STANDARD_DEVIATION 1.66	3.8 Therapies STANDARD_DEVIATION 1.65
Number of Previous TKI Therapies	1.6 Therapies STANDARD_DEVIATION 0.86	1.8 Therapies STANDARD_DEVIATION 0.75	1.6 Therapies STANDARD_DEVIATION 0.86	1.6 Therapies STANDARD_DEVIATION 0.77	1.5 Therapies STANDARD_DEVIATION 0.87	2.3 Therapies STANDARD_DEVIATION 1.48	1.7 Therapies STANDARD_DEVIATION 0.77
Race/Ethnicity, Customized Asian	124 Participants	1 Participants	24 Participants	49 Participants	41 Participants	4 Participants	5 Participants
Race/Ethnicity, Customized Black or African American	17 Participants	0 Participants	2 Participants	8 Participants	7 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Other	103 Participants	0 Participants	5 Participants	51 Participants	39 Participants	2 Participants	6 Participants
Race/Ethnicity, Customized White	368 Participants	5 Participants	64 Participants	137 Participants	122 Participants	13 Participants	27 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	124 Participants	1 Participants	24 Participants	49 Participants	41 Participants	4 Participants	5 Participants
Race (NIH/OMB) Black or African American	17 Participants	0 Participants	2 Participants	8 Participants	7 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	7 Participants	0 Participants	0 Participants	3 Participants	4 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	94 Participants	0 Participants	5 Participants	46 Participants	35 Participants	2 Participants	6 Participants
Race (NIH/OMB) White	368 Participants	5 Participants	64 Participants	137 Participants	122 Participants	13 Participants	27 Participants
Sex: Female, Male Female	424 Participants	5 Participants	63 Participants	155 Participants	155 Participants	15 Participants	31 Participants
Sex: Female, Male Male	188 Participants	1 Participants	32 Participants	90 Participants	54 Participants	4 Participants	7 Participants
T790M Status ( Determined by Central Lab) Missing	59 Participants	0 Participants	5 Participants	43 Participants	11 Participants	0 Participants	0 Participants
T790M Status ( Determined by Central Lab) Negative	49 Participants	0 Participants	9 Participants	25 Participants	6 Participants	4 Participants	5 Participants
T790M Status ( Determined by Central Lab) Positive	480 Participants	4 Participants	80 Participants	176 Participants	188 Participants	9 Participants	23 Participants
T790M Status ( Determined by Central Lab) Unknown	24 Participants	2 Participants	1 Participants	1 Participants	4 Participants	6 Participants	10 Participants
Time Since Diagnosis of NSCLC (months)	37.4 Months STANDARD_DEVIATION 29.17	47.4 Months STANDARD_DEVIATION 27.03	37.6 Months STANDARD_DEVIATION 29.97	36.7 Months STANDARD_DEVIATION 31.41	36.7 Months STANDARD_DEVIATION 25.81	45.4 Months STANDARD_DEVIATION 31.94	40.4 Months STANDARD_DEVIATION 29.2

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	4 / 38	4 / 19	31 / 209	40 / 245	19 / 95	3 / 6
other Total, other adverse events	37 / 38	19 / 19	208 / 209	244 / 245	95 / 95	6 / 6
serious Total, serious adverse events	14 / 38	8 / 19	106 / 209	138 / 245	54 / 95	5 / 6

Outcome results

Primary

Dose Limiting Toxicity (DLT) Incidence

The number of Phase 1 patients who experienced dose limiting toxicities after one cycle (21 days) of study drug.

Time frame: Cycle 1 Day 1 to Cycle 1 Day 21

Population: The dose limiting toxicity (DLT) evaluable population includes all patients who have completed Cycle 1, and who were enrolled while the dose escalation (Phase 1) part of the study was ongoing.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Rociletinib <900 mg BID FB Capsules	Dose Limiting Toxicity (DLT) Incidence	1 Participants
Rociletinib 900 mg BID FB Capsules	Dose Limiting Toxicity (DLT) Incidence	1 Participants
Rociletinib 500 mg BID HBr Tablets	Dose Limiting Toxicity (DLT) Incidence	1 Participants
Rociletinib 625 mg BID HBr Tablets	Dose Limiting Toxicity (DLT) Incidence	2 Participants
Rociletinib 750 mg BID HBr Tablets	Dose Limiting Toxicity (DLT) Incidence	1 Participants
Rociletinib 1000 mg BID HBr Tablets	Dose Limiting Toxicity (DLT) Incidence	1 Participants

Primary

Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment

Duration of Response in patients with a T790M mutation (determined by central lab) with confirmed response per investigator. The DOR for complete response (CR) and partial response (PR) was measured from the date that any of these best responses is first recorded until the first date that progressive disease (PD) is objectively documented. For patients who continue treatment post-progression, the first date of progression was used for the analysis.

Time frame: Cycle 1 Day 1 to End of Treatment, up to approximately 36 months

Population: The DOR was measured only in T790M positive patients with a Complete Response (CR) or Partial Response (PR). There were no responders in the Rociletinib \<900 mg BID treatment group so DOR is not applicable and thus not reported.

Arm	Measure	Value (MEDIAN)
Rociletinib <900 mg BID FB Capsules	Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment	329.0 Days
Rociletinib 900 mg BID FB Capsules	Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment	275.0 Days
Rociletinib 500 mg BID HBr Tablets	Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment	274.0 Days
Rociletinib 625 mg BID HBr Tablets	Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment	217.0 Days
Rociletinib 750 mg BID HBr Tablets	Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment	428 Days

Primary

Percentage of T790M Positive Patients With Confirmed Response Per Investigator

Percentage of patients with a T790M mutation (determined by central lab) with a best overall confirmed response of partial response (PR) or complete response (CR) recorded from the start of the treatment until disease progression or recurrence. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR),at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

Time frame: Cycle 1 Day 1 to End of Treatment, up to approximately 42 months

Population: Intent-to-treat: All randomized patients who are confirmed by central lab to be T790M positive

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Rociletinib <900 mg BID FB Capsules	Percentage of T790M Positive Patients With Confirmed Response Per Investigator	0 Participants
Rociletinib 900 mg BID FB Capsules	Percentage of T790M Positive Patients With Confirmed Response Per Investigator	3 Participants
Rociletinib 500 mg BID HBr Tablets	Percentage of T790M Positive Patients With Confirmed Response Per Investigator	54 Participants
Rociletinib 625 mg BID HBr Tablets	Percentage of T790M Positive Patients With Confirmed Response Per Investigator	72 Participants
Rociletinib 750 mg BID HBr Tablets	Percentage of T790M Positive Patients With Confirmed Response Per Investigator	23 Participants
Rociletinib 1000 mg BID HBr Tablets	Percentage of T790M Positive Patients With Confirmed Response Per Investigator	3 Participants

Secondary

Food Effect on PK of Rociletinib - AUC 0-24

AUC 0-24 = area under the curve from 0 to 24 hours. The effect of food on rociletinib PK parameters was assessed over a 24-hour period in blood samples from a subset of 3 patients. These patients were given a single dose of rociletinib 150mg FB 1 week prior (Day -7) to the start of continuous daily dosing after fasting. On Day 1 of Cycle 1, patients consumed a high-fat, high-calorie breakfast at the study site prior to receiving rociletinib. On each day, patients underwent blood sampling for PK at the specified time points.