Non-small Cell Lung Cancer
Conditions
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
The purpose of this study is to evaluate the safety and anti-tumor effect of rociletinib. The trial is open-ended, which means patients will continue to take rociletinib until the study doctor determines it is no longer beneficial for them.
Detailed description
This is a Phase 2, single arm, open-label, dual cohort, multicenter study evaluating the safety and efficacy of rociletinib administered orally to patients with previously treated mutant EGFR NSCLC. Patients will be enrolled into 2 cohorts. Cohort A will enroll approximately 125 eligible patients who are centrally confirmed T790M-positive. Cohort B will be a continuation of the study and will enroll up to approximately 100 eligible patients who will be either centrally confirmed T790M-positive or T790M-negative. All patients (for Cohort A and B) should have experienced disease progression while on treatment with the first single-agent EGFR-directed TKI (EGFR-TKI) for advanced/metastatic NSCLC. One line of chemotherapy prior to the EGFR-TKI treatment is permissible. The study (Cohorts A and B) will consist of a screening phase to establish study eligibility and document baseline measurements, an open-label treatment phase, in which the patient will receive rociletinib to ascertain safety and efficacy until disease progression as defined by RECIST Version 1.1, clinical tumor progression, or unacceptable toxicity as assessed by the investigator. For patients with clinical progression, radiographic assessment should be performed to document evidence of radiographic progression.
Interventions
DRUGRociletinib
Rociletinib will be administered to patients orally
Sponsors
Clovis Oncology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC * Documented evidence of a tumor with 1 or more EGFR mutations excluding exon 20 insertion * Disease progression confirmed by radiologic assessment while receiving treatment with the first single agent EGFR-TKI * EGFR TKI treatment discontinued less than or equal to 30 days prior to planned initiation of rociletinib * The washout period for an EGFR inhibitor is a minimum of 3 days * No intervening treatment between cessation of single agent EGFR TKI and planned initiation of rociletinib * Previous treatment with less than or equal to 1 prior chemotherapy (excluding prior neo-adjuvant or adjuvant chemotherapy or chemoradiotherapy with curative intent) * Any toxicity related to prior EGFR inhibitor treatment must have resolved to Grade 1 or less * Central laboratory confirmation of the presence of the T790M mutation in tumor tissue in Cohort A and the presence or absence of the T790M mutation in tumor tissue in Cohort B. Centrally indeterminate, unknown or invalid specimens are not acceptable. Biopsy material obtained from either primary or metastatic tumor tissue and sent to the central laboratory must be within 60 prior to dosing study drug but following disease progression on the first EGFR TKI * Measurable disease according to RECIST Version 1.1 * Life expectancy of at least 3 months * ECOG performance status of 0 to 1 * Minimum Age 18 years (in certain territories, the minimum age requirement may be higher eg age 20 years in Japan and Taiwan) * Adequate hematological and biological function, confirmed by defined laboratory values * Written consent on an IRB/IEC-approved Informed Consent Form (ICF) prior to any study specific evaluation
Exclusion criteria
* Documented evidence of an exon 20 insertion activating mutation in the EGFR gene * 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 * Patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enrol in the trial provided all chemotherapy was completed greater than 6 months prior and/or bone marrow transplant greater than 2 years prior * Known pre-existing interstitial lung disease * Cohort A only: Patients with leptomeningeal carcinomatosis are excluded. Other central nervous system (CNS) metastases are only permitted if treated, asymptomatic, and stable (not requiring steroid for at least 4 weeks prior to the start of study treatment). Cohort B only: Patients with CNS metastases or leptomeningeal carcinomatosis are excluded. * Treatment with prohibited medications less than or equal to 14 days prior to treatment with rociletinib * 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 * Prior treatment with rociletinib, or other drugs that target T790M positive mutant EGFR with sparing of wild type EGFR * Any of the following cardiac abnormalities or history * Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTCF) greater than 450 msec * Inability to measure QT interval on ECG * Personal or family history of long QT syndrome * Implantable pacemaker or implantable cardioverter defibrillator * Resting bradycardia less than 55 beats/min * Non-study related surgical procedures less than or equal to 7 days prior to administration of rociletinib. In all cases, the patient must be sufficiently recovered and stable before treatment administration * Females who are pregnant or breastfeeding * Refusal to use adequate contraception for fertile patients (females and males) while on treatment and for 12 weeks after the last dose of rociletinib * Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study * Any other reason the investigator considers the patient should not participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) According to RECIST Version 1.1 as Determined by Investigator Assessment | Cycle 1 Day 1 to End of Treatment, up to approximately 57 months. | ORR is defined as the percentage of patients with a best overall confirmed response of partial response (PR) or complete response (CR) recorded from the start of the treatment until disease progression. For patients who continued treatment post-progression, the first date of progression was used for the analysis. 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) by RECIST v1.1 as Determined by Investigator Assessment | From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 57 months | DCR is defined as the percentage of patients who have achieved CR, PR, and SD lasting at least 12 weeks. 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. Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since the treatment started. |
| Progression-free Survival (PFS) in T790M Positive Patients by RECIST v1.1 as Determined by Investigator Assessment | From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 57 months | PFS was calculated as 1+ the number of days from the first dose of study drug to documented radiographic progression or death due to any cause, whichever occurs first. Patients without a documented event of radiographic 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 were performed. For patients who continued treatment post-progression, the first date of progression was used for the analysis of PFS. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), 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. |
| Overall Survival (OS) Determined by Investigator Assessment | Cycle 1 Day 1 to date of death, assessed up to 57 months | OS 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 will be censored on the date the patient was last known to be alive. |
| Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Quality of Life Scale | Baseline (Day 0), Months 5, 10 and EOT | EORTC QLC-C30 is a 30-item questionnaire to assess the quality of life in cancer patients. EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnoea, appetite loss, insomnia, constipation/diarrhea, financial difficulties). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); two used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better quality of life. |
| Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in Dermatology Life Quality Index (DLQI) | Baseline (Day 0), Months 5, 10 and EOT | Dermatology Life Quality Index (DLQI) score is a participant-reported outcome consisting of a set of 10 questions regarding the degree to which the participant's skin has affected certain behaviors and quality of life over the last week. Responses to each are: very much (score of 3), a lot, a little, or not at all (score of 0). The DLQI score ranges from 0 (best) to 30 (worst); the higher the score, the more quality of life is impaired. |
| Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Alopecia Scale | Baseline (Day 0), Months 5, 10 and EOT | EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms. |
| Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Coughing Scale | Baseline (Day 0), Months 5, 10 and EOT | EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms. |
| Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dysphagia Scale | Baseline (Day 0), Months 5, 10 and EOT | EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms. |
| Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment | From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 54 months | DOR 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. |
| Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Haemoptysis Scale | Baseline (Day 0), Months 5, 10 and EOT | EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms. |
| Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Arm or Shoulder Scale | Baseline (Day 0), Months 5, 10 and EOT | EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms. |
| Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Chest Scale | Baseline (Day 0), Months 5, 10 and EOT | EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms. |
| Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Medicine for Pain Scale | Baseline (Day 0), Months 5, 10 and EOT | EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms. |
| Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Other Parts Scale | Baseline (Day 0), Months 5, 10 and EOT | EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms. |
| Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Peripheral Neuropathy Scale | Baseline (Day 0), Months 5, 10 and EOT | EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms. |
| Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Sore Mouth Scale | Baseline (Day 0), Months 5, 10 and EOT | EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms. |
| Population PK (POPPK) and Exposure-Response (ER) Analysis of Rociletinib | Every 4 weeks for approximately 6 months (Day 1 of Cycles 2 to 7 inclusive) | Sparse blood sampling for POPPK and ER analyses in all patients treated with rociletinib. |
| Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dyspnoea Scale | Baseline (Day 0), Months 5, 10 and EOT | EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms. |
Countries
Australia, Canada, France, Germany, Hong Kong, Netherlands, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
318 patients were enrolled at 67 study sites in North America, Europe, Asia and Australia. One patient was not included in the Safety Population due to failure of the study site to provide any dosing data in electronic data capture (EDC) before the site was closed.
Participants by arm
| Arm | Count |
|---|---|
| Rociletinib 625 mg BID T790M+ Rociletinib 625 mg BID in patients with T790M-positive tumor status | 154 |
| Rociletinib 500 mg BID T790M+ Rociletinib 500 mg BID in patients with T790M-positive tumor status | 100 |
| Rociletinib 500 mg BID T790M- Rociletinib 500 mg BID in patients with T790M-negative tumor status | 63 |
| Total | 317 |
Baseline characteristics
| Characteristic | Rociletinib 625 mg BID T790M+ | Rociletinib 500 mg BID T790M+ | Rociletinib 500 mg BID T790M- | Total |
|---|---|---|---|---|
| Age, Continuous | 62.8 years STANDARD_DEVIATION 10.67 | 65.3 years STANDARD_DEVIATION 9.93 | 64.1 years STANDARD_DEVIATION 10.01 | 63.8 years STANDARD_DEVIATION 10.34 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 3 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 131 Participants | 93 Participants | 55 Participants | 279 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 21 Participants | 5 Participants | 5 Participants | 31 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 59 Participants | 34 Participants | 32 Participants | 125 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 5 Participants | 2 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 14 Participants | 3 Participants | 6 Participants | 23 Participants |
| Race (NIH/OMB) White | 74 Participants | 58 Participants | 23 Participants | 155 Participants |
| Sex: Female, Male Female | 105 Participants | 69 Participants | 41 Participants | 215 Participants |
| Sex: Female, Male Male | 49 Participants | 31 Participants | 22 Participants | 102 Participants |
| T790M Status Missing | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| T790M Status T790M Negative | 1 Participants | 0 Participants | 62 Participants | 63 Participants |
| T790M Status T790M Positive | 153 Participants | 100 Participants | 0 Participants | 253 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 27 / 154 | 7 / 100 | 9 / 63 |
| other Total, other adverse events | 153 / 154 | 100 / 100 | 63 / 63 |
| serious Total, serious adverse events | 77 / 154 | 48 / 100 | 34 / 63 |
Outcome results
Primary
Objective Response Rate (ORR) According to RECIST Version 1.1 as Determined by Investigator Assessment
ORR is defined as the percentage of patients with a best overall confirmed response of partial response (PR) or complete response (CR) recorded from the start of the treatment until disease progression. For patients who continued treatment post-progression, the first date of progression was used for the analysis. 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 57 months.
Population: Investigator Tumor Evaluable Population - defined as all patients who received at least 1 dose of rociletinib, have at least 1 measureable tumor lesion at baseline, and have at least 1 post-baseline tumor assessment as determined by the investigator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rociletinib 625 mg BID T790M+ | Objective Response Rate (ORR) According to RECIST Version 1.1 as Determined by Investigator Assessment | 34.6 percentage of participants |
| Rociletinib 500 mg BID T790M+ | Objective Response Rate (ORR) According to RECIST Version 1.1 as Determined by Investigator Assessment | 34.0 percentage of participants |
| Rociletinib 500 mg BID T790M- | Objective Response Rate (ORR) According to RECIST Version 1.1 as Determined by Investigator Assessment | 18.0 percentage of participants |
Secondary
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in Dermatology Life Quality Index (DLQI)
Dermatology Life Quality Index (DLQI) score is a participant-reported outcome consisting of a set of 10 questions regarding the degree to which the participant's skin has affected certain behaviors and quality of life over the last week. Responses to each are: very much (score of 3), a lot, a little, or not at all (score of 0). The DLQI score ranges from 0 (best) to 30 (worst); the higher the score, the more quality of life is impaired.
Time frame: Baseline (Day 0), Months 5, 10 and EOT
Population: Safety population - defined as all patients who received at least 1 dose of rociletinib.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in Dermatology Life Quality Index (DLQI) | Baseline (Day 0) | 2.10 units on a scale | Standard Deviation 3.408 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in Dermatology Life Quality Index (DLQI) | Cycle 5 (approximately month 5) | -0.82 units on a scale | Standard Deviation 3.24 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in Dermatology Life Quality Index (DLQI) | Cycle 10 (approximately month 10) | -1.02 units on a scale | Standard Deviation 2.81 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in Dermatology Life Quality Index (DLQI) | End of Treatment | -0.77 units on a scale | Standard Deviation 3.191 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in Dermatology Life Quality Index (DLQI) | End of Treatment | -0.22 units on a scale | Standard Deviation 2.157 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in Dermatology Life Quality Index (DLQI) | Baseline (Day 0) | 2.42 units on a scale | Standard Deviation 4.706 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in Dermatology Life Quality Index (DLQI) | Cycle 10 (approximately month 10) | -1.64 units on a scale | Standard Deviation 3.531 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in Dermatology Life Quality Index (DLQI) | Cycle 5 (approximately month 5) | -1.29 units on a scale | Standard Deviation 3.499 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in Dermatology Life Quality Index (DLQI) | End of Treatment | -1.14 units on a scale | Standard Deviation 4.204 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in Dermatology Life Quality Index (DLQI) | Cycle 5 (approximately month 5) | -1.63 units on a scale | Standard Deviation 3.731 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in Dermatology Life Quality Index (DLQI) | Cycle 10 (approximately month 10) | -0.79 units on a scale | Standard Deviation 2.751 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in Dermatology Life Quality Index (DLQI) | Baseline (Day 0) | 2.74 units on a scale | Standard Deviation 4.763 |
Secondary
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Alopecia Scale
EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Time frame: Baseline (Day 0), Months 5, 10 and EOT
Population: Safety population - defined as all patients who received at least 1 dose of rociletinib.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Alopecia Scale | Baseline (Day 0) | 9.96 units on a scale | Standard Deviation 21.264 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Alopecia Scale | Cycle 5 (approximately month 5) | -4.62 units on a scale | Standard Deviation 27.499 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Alopecia Scale | Cycle 10 (approximately month 10) | -2.00 units on a scale | Standard Deviation 21.728 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Alopecia Scale | End of Treatment | 4.50 units on a scale | Standard Deviation 33.483 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Alopecia Scale | End of Treatment | 3.51 units on a scale | Standard Deviation 44.298 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Alopecia Scale | Baseline (Day 0) | 9.43 units on a scale | Standard Deviation 20.779 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Alopecia Scale | Cycle 10 (approximately month 10) | -6.67 units on a scale | Standard Deviation 25.309 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Alopecia Scale | Cycle 5 (approximately month 5) | -2.69 units on a scale | Standard Deviation 27.855 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Alopecia Scale | End of Treatment | 0.00 units on a scale | Standard Deviation 39.841 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Alopecia Scale | Cycle 5 (approximately month 5) | -10.10 units on a scale | Standard Deviation 19.516 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Alopecia Scale | Cycle 10 (approximately month 10) | -2.56 units on a scale | Standard Deviation 21.35 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Alopecia Scale | Baseline (Day 0) | 19.05 units on a scale | Standard Deviation 29.154 |
Secondary
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Coughing Scale
EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Time frame: Baseline (Day 0), Months 5, 10 and EOT
Population: Safety population - defined as all patients who received at least 1 dose of rociletinib.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Coughing Scale | Cycle 10 (approximately month 10) | -6.67 units on a scale | Standard Deviation 23.328 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Coughing Scale | End of Treatment | -5.41 units on a scale | Standard Deviation 27.793 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Coughing Scale | Baseline (Day 0) | 33.12 units on a scale | Standard Deviation 26.54 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Coughing Scale | Cycle 5 (approximately month 5) | -7.92 units on a scale | Standard Deviation 26.728 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Coughing Scale | Cycle 10 (approximately month 10) | -17.14 units on a scale | Standard Deviation 30.648 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Coughing Scale | Cycle 5 (approximately month 5) | -9.29 units on a scale | Standard Deviation 26.619 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Coughing Scale | End of Treatment | 0.00 units on a scale | Standard Deviation 36.851 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Coughing Scale | Baseline (Day 0) | 29.97 units on a scale | Standard Deviation 25.862 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Coughing Scale | End of Treatment | 6.67 units on a scale | Standard Deviation 25.82 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Coughing Scale | Baseline (Day 0) | 38.62 units on a scale | Standard Deviation 23.346 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Coughing Scale | Cycle 5 (approximately month 5) | -12.12 units on a scale | Standard Deviation 27.409 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Coughing Scale | Cycle 10 (approximately month 10) | 2.56 units on a scale | Standard Deviation 21.35 |
Secondary
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dysphagia Scale
EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Time frame: Baseline (Day 0), Months 5, 10 and EOT
Population: Safety population - defined as all patients who received at least 1 dose of rociletinib.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dysphagia Scale | Cycle 5 (approximately month 5) | 1.65 units on a scale | Standard Deviation 12.803 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dysphagia Scale | Baseline (Day 0) | 5.19 units on a scale | Standard Deviation 15.306 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dysphagia Scale | Cycle 10 (approximately month 10) | -3.27 units on a scale | Standard Deviation 13.752 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dysphagia Scale | End of Treatment | 3.60 units on a scale | Standard Deviation 17.184 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dysphagia Scale | End of Treatment | 7.41 units on a scale | Standard Deviation 31.427 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dysphagia Scale | Cycle 10 (approximately month 10) | -3.81 units on a scale | Standard Deviation 15.7 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dysphagia Scale | Baseline (Day 0) | 7.41 units on a scale | Standard Deviation 17.532 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dysphagia Scale | Cycle 5 (approximately month 5) | -0.54 units on a scale | Standard Deviation 17.589 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dysphagia Scale | Baseline (Day 0) | 5.82 units on a scale | Standard Deviation 17.495 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dysphagia Scale | Cycle 5 (approximately month 5) | 7.07 units on a scale | Standard Deviation 21.663 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dysphagia Scale | Cycle 10 (approximately month 10) | 2.56 units on a scale | Standard Deviation 9.245 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dysphagia Scale | End of Treatment | 6.67 units on a scale | Standard Deviation 28.73 |
Secondary
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dyspnoea Scale
EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Time frame: Baseline (Day 0), Months 5, 10 and EOT
Population: Safety population - defined as all patients who received at least 1 dose of rociletinib.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dyspnoea Scale | Baseline (Day 0) | 21.79 units on a scale | Standard Deviation 21.554 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dyspnoea Scale | Cycle 5 (approximately month 5) | 6.11 units on a scale | Standard Deviation 21.681 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dyspnoea Scale | Cycle 10 (approximately month 10) | 2.83 units on a scale | Standard Deviation 19.606 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dyspnoea Scale | End of Treatment | 8.41 units on a scale | Standard Deviation 22.892 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dyspnoea Scale | End of Treatment | 8.77 units on a scale | Standard Deviation 18.362 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dyspnoea Scale | Baseline (Day 0) | 22.56 units on a scale | Standard Deviation 21.441 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dyspnoea Scale | Cycle 10 (approximately month 10) | 1.90 units on a scale | Standard Deviation 14.879 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dyspnoea Scale | Cycle 5 (approximately month 5) | -1.25 units on a scale | Standard Deviation 18.777 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dyspnoea Scale | End of Treatment | 0.00 units on a scale | Standard Deviation 28.172 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dyspnoea Scale | Cycle 5 (approximately month 5) | -3.70 units on a scale | Standard Deviation 23.516 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dyspnoea Scale | Cycle 10 (approximately month 10) | 6.84 units on a scale | Standard Deviation 22.923 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dyspnoea Scale | Baseline (Day 0) | 30.34 units on a scale | Standard Deviation 26.415 |
Secondary
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Haemoptysis Scale
EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Time frame: Baseline (Day 0), Months 5, 10 and EOT
Population: Safety population - defined as all patients who received at least 1 dose of rociletinib.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Haemoptysis Scale | Baseline (Day 0) | 2.38 units on a scale | Standard Deviation 8.613 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Haemoptysis Scale | Cycle 5 (approximately month 5) | -1.98 units on a scale | Standard Deviation 7.919 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Haemoptysis Scale | Cycle 10 (approximately month 10) | -0.65 units on a scale | Standard Deviation 8.138 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Haemoptysis Scale | End of Treatment | -0.90 units on a scale | Standard Deviation 12.389 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Haemoptysis Scale | End of Treatment | 0.00 units on a scale | Standard Deviation 0 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Haemoptysis Scale | Baseline (Day 0) | 1.68 units on a scale | Standard Deviation 11.039 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Haemoptysis Scale | Cycle 10 (approximately month 10) | -0.95 units on a scale | Standard Deviation 5.634 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Haemoptysis Scale | Cycle 5 (approximately month 5) | -1.61 units on a scale | Standard Deviation 9.404 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Haemoptysis Scale | End of Treatment | -2.22 units on a scale | Standard Deviation 8.607 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Haemoptysis Scale | Cycle 5 (approximately month 5) | -5.21 units on a scale | Standard Deviation 14.93 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Haemoptysis Scale | Cycle 10 (approximately month 10) | -5.13 units on a scale | Standard Deviation 18.49 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Haemoptysis Scale | Baseline (Day 0) | 4.76 units on a scale | Standard Deviation 13.194 |
Secondary
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Medicine for Pain Scale
EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Time frame: Baseline (Day 0), Months 5, 10 and EOT
Population: Safety population - defined as all patients who received at least 1 dose of rociletinib.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Medicine for Pain Scale | Baseline (Day 0) | 60.47 units on a scale | Standard Deviation 27.302 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Medicine for Pain Scale | Cycle 5 (approximately month 5) | 6.67 units on a scale | Standard Deviation 35.45 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Medicine for Pain Scale | Cycle 10 (approximately month 10) | 4.76 units on a scale | Standard Deviation 12.105 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Medicine for Pain Scale | End of Treatment | 3.92 units on a scale | Standard Deviation 20.008 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Medicine for Pain Scale | End of Treatment | 0.00 units on a scale | Standard Deviation 30.861 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Medicine for Pain Scale | Baseline (Day 0) | 66.67 units on a scale | Standard Deviation 27.766 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Medicine for Pain Scale | Cycle 10 (approximately month 10) | -4.17 units on a scale | Standard Deviation 27.817 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Medicine for Pain Scale | Cycle 5 (approximately month 5) | 8.89 units on a scale | Standard Deviation 23.458 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Medicine for Pain Scale | End of Treatment | -5.56 units on a scale | Standard Deviation 38.968 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Medicine for Pain Scale | Cycle 5 (approximately month 5) | -4.76 units on a scale | Standard Deviation 36.648 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Medicine for Pain Scale | Cycle 10 (approximately month 10) | 22.22 units on a scale | Standard Deviation 19.245 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Medicine for Pain Scale | Baseline (Day 0) | 53.17 units on a scale | Standard Deviation 23.35 |
Secondary
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Arm or Shoulder Scale
EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Time frame: Baseline (Day 0), Months 5, 10 and EOT
Population: Safety population - defined as all patients who received at least 1 dose of rociletinib.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Arm or Shoulder Scale | Baseline (Day 0) | 19.91 units on a scale | Standard Deviation 26.271 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Arm or Shoulder Scale | Cycle 5 (approximately month 5) | -5.94 units on a scale | Standard Deviation 32.11 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Arm or Shoulder Scale | Cycle 10 (approximately month 10) | -1.31 units on a scale | Standard Deviation 31.242 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Arm or Shoulder Scale | End of Treatment | 5.41 units on a scale | Standard Deviation 29.932 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Arm or Shoulder Scale | End of Treatment | 0.00 units on a scale | Standard Deviation 35.136 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Arm or Shoulder Scale | Baseline (Day 0) | 16.67 units on a scale | Standard Deviation 26.325 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Arm or Shoulder Scale | Cycle 10 (approximately month 10) | -2.86 units on a scale | Standard Deviation 27.262 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Arm or Shoulder Scale | Cycle 5 (approximately month 5) | -2.69 units on a scale | Standard Deviation 25.819 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Arm or Shoulder Scale | End of Treatment | 4.44 units on a scale | Standard Deviation 33.014 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Arm or Shoulder Scale | Cycle 5 (approximately month 5) | -7.29 units on a scale | Standard Deviation 35.655 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Arm or Shoulder Scale | Cycle 10 (approximately month 10) | 8.33 units on a scale | Standard Deviation 28.868 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Arm or Shoulder Scale | Baseline (Day 0) | 28.42 units on a scale | Standard Deviation 34.338 |
Secondary
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Chest Scale
EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Time frame: Baseline (Day 0), Months 5, 10 and EOT
Population: Safety population - defined as all patients who received at least 1 dose of rociletinib.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Chest Scale | Baseline (Day 0) | 19.91 units on a scale | Standard Deviation 25.429 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Chest Scale | Cycle 5 (approximately month 5) | -4.62 units on a scale | Standard Deviation 25.399 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Chest Scale | Cycle 10 (approximately month 10) | -3.27 units on a scale | Standard Deviation 24.272 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Chest Scale | End of Treatment | 1.80 units on a scale | Standard Deviation 34.198 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Chest Scale | End of Treatment | 7.02 units on a scale | Standard Deviation 13.962 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Chest Scale | Baseline (Day 0) | 12.79 units on a scale | Standard Deviation 22.691 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Chest Scale | Cycle 10 (approximately month 10) | -6.86 units on a scale | Standard Deviation 19.728 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Chest Scale | Cycle 5 (approximately month 5) | -5.38 units on a scale | Standard Deviation 20.194 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Chest Scale | End of Treatment | -4.44 units on a scale | Standard Deviation 30.516 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Chest Scale | Cycle 5 (approximately month 5) | -8.08 units on a scale | Standard Deviation 28.904 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Chest Scale | Cycle 10 (approximately month 10) | 2.56 units on a scale | Standard Deviation 39.585 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Chest Scale | Baseline (Day 0) | 25.40 units on a scale | Standard Deviation 32.635 |
Secondary
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Other Parts Scale
EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Time frame: Baseline (Day 0), Months 5, 10 and EOT
Population: Safety population - defined as all patients who received at least 1 dose of rociletinib.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Other Parts Scale | Baseline (Day 0) | 28.41 units on a scale | Standard Deviation 30.848 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Other Parts Scale | Cycle 5 (approximately month 5) | 2.46 units on a scale | Standard Deviation 34.464 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Other Parts Scale | Cycle 10 (approximately month 10) | -3.47 units on a scale | Standard Deviation 28.55 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Other Parts Scale | End of Treatment | 20.59 units on a scale | Standard Deviation 31.798 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Other Parts Scale | End of Treatment | 0.00 units on a scale | Standard Deviation 26.352 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Other Parts Scale | Baseline (Day 0) | 30.58 units on a scale | Standard Deviation 33.219 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Other Parts Scale | Cycle 10 (approximately month 10) | -6.67 units on a scale | Standard Deviation 31.102 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Other Parts Scale | Cycle 5 (approximately month 5) | -1.13 units on a scale | Standard Deviation 29.664 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Other Parts Scale | End of Treatment | 6.67 units on a scale | Standard Deviation 44.006 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Other Parts Scale | Cycle 5 (approximately month 5) | -7.78 units on a scale | Standard Deviation 33.543 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Other Parts Scale | Cycle 10 (approximately month 10) | -2.78 units on a scale | Standard Deviation 22.285 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Other Parts Scale | Baseline (Day 0) | 31.69 units on a scale | Standard Deviation 29.456 |
Secondary
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Peripheral Neuropathy Scale
EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Time frame: Baseline (Day 0), Months 5, 10 and EOT
Population: Safety population - defined as all patients who received at least 1 dose of rociletinib.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Peripheral Neuropathy Scale | Cycle 10 (approximately month 10) | 4.58 units on a scale | Standard Deviation 25.837 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Peripheral Neuropathy Scale | Cycle 5 (approximately month 5) | 0.00 units on a scale | Standard Deviation 25.386 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Peripheral Neuropathy Scale | Baseline (Day 0) | 11.90 units on a scale | Standard Deviation 22.117 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Peripheral Neuropathy Scale | End of Treatment | 2.70 units on a scale | Standard Deviation 21.341 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Peripheral Neuropathy Scale | Cycle 10 (approximately month 10) | 2.86 units on a scale | Standard Deviation 18.737 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Peripheral Neuropathy Scale | Baseline (Day 0) | 6.40 units on a scale | Standard Deviation 17.611 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Peripheral Neuropathy Scale | Cycle 5 (approximately month 5) | 3.76 units on a scale | Standard Deviation 23.458 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Peripheral Neuropathy Scale | End of Treatment | 7.02 units on a scale | Standard Deviation 26.244 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Peripheral Neuropathy Scale | Baseline (Day 0) | 17.20 units on a scale | Standard Deviation 29.409 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Peripheral Neuropathy Scale | Cycle 10 (approximately month 10) | 0.00 units on a scale | Standard Deviation 20.101 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Peripheral Neuropathy Scale | End of Treatment | 2.22 units on a scale | Standard Deviation 15.258 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Peripheral Neuropathy Scale | Cycle 5 (approximately month 5) | 4.17 units on a scale | Standard Deviation 31.395 |
Secondary
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Sore Mouth Scale
EORTC QLQ-LC13 is the lung cancer module of EORTC QLQ-C30 and includes questions specific to the disease associated symptoms (dyspnea, cough, hemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy and alopecia), and analgesic use of lung cancer patients. The scale was transformed to a range of 0 to 100 using standard EORTC algorithm. Higher score indicates worse symptoms.
Time frame: Baseline (Day 0), Months 5, 10 and EOT
Population: Safety population - defined as all patients who received at least 1 dose of rociletinib.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Sore Mouth Scale | Cycle 10 (approximately month 10) | 0.65 units on a scale | Standard Deviation 19.425 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Sore Mouth Scale | End of Treatment | 4.50 units on a scale | Standard Deviation 21.026 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Sore Mouth Scale | Cycle 5 (approximately month 5) | 1.98 units on a scale | Standard Deviation 18.149 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Sore Mouth Scale | Baseline (Day 0) | 5.19 units on a scale | Standard Deviation 13.273 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Sore Mouth Scale | Baseline (Day 0) | 7.41 units on a scale | Standard Deviation 17.532 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Sore Mouth Scale | Cycle 5 (approximately month 5) | -2.19 units on a scale | Standard Deviation 21.832 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Sore Mouth Scale | End of Treatment | 12.28 units on a scale | Standard Deviation 29.836 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Sore Mouth Scale | Cycle 10 (approximately month 10) | -1.90 units on a scale | Standard Deviation 24.176 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Sore Mouth Scale | End of Treatment | 2.22 units on a scale | Standard Deviation 36.659 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Sore Mouth Scale | Baseline (Day 0) | 10.58 units on a scale | Standard Deviation 21.44 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Sore Mouth Scale | Cycle 5 (approximately month 5) | -2.02 units on a scale | Standard Deviation 27.562 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Sore Mouth Scale | Cycle 10 (approximately month 10) | 2.56 units on a scale | Standard Deviation 21.35 |
Secondary
Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Quality of Life Scale
EORTC QLC-C30 is a 30-item questionnaire to assess the quality of life in cancer patients. EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnoea, appetite loss, insomnia, constipation/diarrhea, financial difficulties). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); two used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better quality of life.
Time frame: Baseline (Day 0), Months 5, 10 and EOT
Population: Safety population - defined as all patients who received at least 1 dose of rociletinib.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Quality of Life Scale | Baseline (Day 0) | 62.18 units on a scale | Standard Deviation 22.245 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Quality of Life Scale | Cycle 5 (approximately month 5) | -2.48 units on a scale | Standard Deviation 22.47 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Quality of Life Scale | Cycle 10 (approximately month 10) | -2.21 units on a scale | Standard Deviation 22.294 |
| Rociletinib 625 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Quality of Life Scale | End of Treatment | -4.82 units on a scale | Standard Deviation 23.381 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Quality of Life Scale | End of Treatment | -9.65 units on a scale | Standard Deviation 18.481 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Quality of Life Scale | Baseline (Day 0) | 59.76 units on a scale | Standard Deviation 22.495 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Quality of Life Scale | Cycle 10 (approximately month 10) | -3.81 units on a scale | Standard Deviation 21.422 |
| Rociletinib 500 mg BID T790M+ | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Quality of Life Scale | Cycle 5 (approximately month 5) | -0.56 units on a scale | Standard Deviation 23.763 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Quality of Life Scale | End of Treatment | -10.42 units on a scale | Standard Deviation 35.158 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Quality of Life Scale | Cycle 5 (approximately month 5) | 5.56 units on a scale | Standard Deviation 28.842 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Quality of Life Scale | Cycle 10 (approximately month 10) | 3.57 units on a scale | Standard Deviation 23.956 |
| Rociletinib 500 mg BID T790M- | Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Quality of Life Scale | Baseline (Day 0) | 54.63 units on a scale | Standard Deviation 24.629 |
Secondary
Disease Control Rate (DCR) by RECIST v1.1 as Determined by Investigator Assessment
DCR is defined as the percentage of patients who have achieved CR, PR, and SD lasting at least 12 weeks. 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. Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since the treatment started.
Time frame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 57 months
Population: Investigator Tumor Evaluable Population - defined as all patients who received at least 1 dose of rociletinib, have at least 1 measureable tumor lesion at baseline, and have at least 1 post-baseline tumor assessment as determined by the investigator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rociletinib 625 mg BID T790M+ | Disease Control Rate (DCR) by RECIST v1.1 as Determined by Investigator Assessment | 67.3 percentage of patients |
| Rociletinib 500 mg BID T790M+ | Disease Control Rate (DCR) by RECIST v1.1 as Determined by Investigator Assessment | 76.3 percentage of patients |
| Rociletinib 500 mg BID T790M- | Disease Control Rate (DCR) by RECIST v1.1 as Determined by Investigator Assessment | 59.0 percentage of patients |
Secondary
Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment
DOR 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: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 54 months
Population: Centrally-confirmed T790M-positive subset of the Investigator Tumor Evaluable Population - defined as all patients who received at least 1 dose of rociletinib, have at least 1 measureable tumor lesion at baseline, and have at least 1 post-baseline tumor assessment as determined by the investigator.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rociletinib 625 mg BID T790M+ | Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment | 7.4 months |
| Rociletinib 500 mg BID T790M+ | Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment | 9.1 months |
| Rociletinib 500 mg BID T790M- | Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment | 7.6 months |
Secondary
Overall Survival (OS) Determined by Investigator Assessment
OS 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 will be censored on the date the patient was last known to be alive.
Time frame: Cycle 1 Day 1 to date of death, assessed up to 57 months
Population: Centrally-confirmed T790M-positive subset of the Intent-to-treat (ITT) population defined as all patients who received at least 1 dose of rociletinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rociletinib 625 mg BID T790M+ | Overall Survival (OS) Determined by Investigator Assessment | 18.8 months |
| Rociletinib 500 mg BID T790M+ | Overall Survival (OS) Determined by Investigator Assessment | 29.8 months |
| Rociletinib 500 mg BID T790M- | Overall Survival (OS) Determined by Investigator Assessment | 23.7 months |
Secondary
Population PK (POPPK) and Exposure-Response (ER) Analysis of Rociletinib
Sparse blood sampling for POPPK and ER analyses in all patients treated with rociletinib.
Time frame: Every 4 weeks for approximately 6 months (Day 1 of Cycles 2 to 7 inclusive)
Population: Population PK (PPK) and exposure-response (ER) analysis were listed as a secondary objective. These analyses were conducted based on pooled data from multiple rociletinib trials (including TIGER2), thus no PPK or ER report was generated specifically for this study.
Secondary
Progression-free Survival (PFS) in T790M Positive Patients by RECIST v1.1 as Determined by Investigator Assessment
PFS was calculated as 1+ the number of days from the first dose of study drug to documented radiographic progression or death due to any cause, whichever occurs first. Patients without a documented event of radiographic 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 were performed. For patients who continued treatment post-progression, the first date of progression was used for the analysis of PFS. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), 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.
Time frame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 57 months
Population: Centrally-confirmed T790M-positive subset of the Intent-to-treat (ITT) population defined as all patients who received at least 1 dose of rociletinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rociletinib 625 mg BID T790M+ | Progression-free Survival (PFS) in T790M Positive Patients by RECIST v1.1 as Determined by Investigator Assessment | 5.5 months |
| Rociletinib 500 mg BID T790M+ | Progression-free Survival (PFS) in T790M Positive Patients by RECIST v1.1 as Determined by Investigator Assessment | 5.9 months |
| Rociletinib 500 mg BID T790M- | Progression-free Survival (PFS) in T790M Positive Patients by RECIST v1.1 as Determined by Investigator Assessment | 5.5 months |