Trial Outcomes & Findings for Phase II Safety and Efficacy Study of Crizotinib in East Asian Patients With ROS1 Positive, ALK Negative Advanced NSCLC (NCT NCT01945021)

NCT ID: NCT01945021

Last Updated: 2021-02-21

Results Overview

Overall objective response (ORR) was defined as the number of patients with a best overall response of confirmed Complete Response or confirmed Partial Response according to RECIST v1.1 (as determined by Independent Radiology Review \[IRR\]), relative to the total population of response-evaluable participants. Per RECIST v1.1, CR: disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis); PR: at least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. Confirmed responses were those that persisted on repeat imaging at least 4 weeks after the initial documentation of response.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

129 participants

Primary outcome timeframe

Starting from the first dose study treatment until the first documented CR or PR (every 8 weeks then after 8 cycles at every 12 weeks in duration of 94.0 weeks)

Results posted on

2021-02-21

Participant Flow

129 participants with anaplastic lymphoma kinase (ALK) negative advanced non-small cell lung cancer (NSCLC) harboring a translocation or inversion event involving the c-ros oncogene 1 (ROS1) locus were enrolled of whom 127 were allocated to treatment with crizotinib and 2 participants had screen failures.

Participant milestones

Participant milestones
Measure	Crizotinib 250 mg Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Overall Study STARTED	127
Overall Study Safety Population	127
Overall Study Response Evaluable Population	127
Overall Study Patient Reported Outcome Evaluable	123
Overall Study COMPLETED	44
Overall Study NOT COMPLETED	83

Reasons for withdrawal

Reasons for withdrawal
Measure	Crizotinib 250 mg Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Overall Study Adverse Event	1
Overall Study Withdrawal of consent	12
Overall Study Lost to Follow-up	5
Overall Study Death	65

Baseline Characteristics

Phase II Safety and Efficacy Study of Crizotinib in East Asian Patients With ROS1 Positive, ALK Negative Advanced NSCLC

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Crizotinib 250 mg n=127 Participants Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Age, Continuous	52.48 Years STANDARD_DEVIATION 12.136 • n=5 Participants
Sex: Female, Male Female	73 Participants n=5 Participants
Sex: Female, Male Male	54 Participants n=5 Participants
Race/Ethnicity, Customized Asian	127 Participants n=5 Participants
Region of Enrollment Asia · China	74 Participants n=5 Participants
Region of Enrollment Asia · Japan	26 Participants n=5 Participants
Region of Enrollment Asia · Korea	12 Participants n=5 Participants
Region of Enrollment Asia · Taiwan	15 Participants n=5 Participants

PRIMARY outcome

Timeframe: Starting from the first dose study treatment until the first documented CR or PR (every 8 weeks then after 8 cycles at every 12 weeks in duration of 94.0 weeks)

Population: The response-evaluable population (RES) population included all enrolled participants who received at least 1 dose of study medication and had an adequate baseline tumor assessment.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg n=127 Participants Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Independent Radiology Reviewed Overall Objective Response (ORR)	88 Participants

SECONDARY outcome

Timeframe: From first documentation of objective tumor response to first documentation of objective PD or death due to any cause, whichever occurred first (every 8 weeks then after 8 cycles at every 12 weeks in duration of 151.3 weeks)

Population: The RES population included all enrolled participants who received at least 1 dose of study medication and had an adequate baseline tumor assessment. Here, "Overall Number of Participants Analyzed" signifies number of participants with a confirmed objective response that could have occurred anytime up to 151.3 weeks.

DR: time from first documentation of objective tumor response (CR or PR) to first documentation of objective progressive disease (PD) or to death due to any cause, whichever occurred first. If no progression or death on study was observed, or given antitumor treatment other than study drug, participants were censored on date of last on-study tumor assessment. RECIST v1.1, a) PD: \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is the smallest on study), sum must also demonstrate an absolute increase of \>=5 mm, appearance of 1 or more new lesions, unequivocal progression of existing non-target lesions; b) CR: disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis); c) PR: \>=30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg n=91 Participants Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
IRR-Assessed Duration of Response (DR)	19.7 Months Interval 14.1 to Upper limit cannot be estimated due to less number of participants with event.

SECONDARY outcome

Timeframe: From date of first dose of crizotinib to first documentation of objective response was observed (every 8 weeks then after 8 cycles at every 12 weeks in duration of 151.3 weeks)

TTR was defined as the time from the date of first dose to first documentation of objective tumor response (CR or PR), that was subsequently confirmed. For participants proceeding from PR to CR, the onset of PR was taken as the onset of response. RECIST v1.1 (as determined by IRR), a) CR: disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis); b) PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg n=91 Participants Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
IRR-Assessed Time to Tumor Response (TTR)	1.9 Months Interval 1.6 to 15.8

SECONDARY outcome

Timeframe: At 8 weeks after the start of study treatment

Population: The RES population included all enrolled participants who received at least 1 dose of study medication and had an adequate baseline tumor assessment.

DCR at 8 weeks was defined as the percentage of participants with a confirmed CR, confirmed PR, or stable disease (SD) at 8 weeks, respectively, relative to the total population of response evaluable participants. RECIST v1.1 (as determined by IRR), a) CR: disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis); b) PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg n=127 Participants Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
IRR Assessed Disease Control Rate (DCR) at 8 Weeks	88.2 Percentage of participants Interval 81.3 to 93.2

SECONDARY outcome

Timeframe: From the date of first dose of crizotinib until the first documentation of objective PD or death (every 8 weeks then after 8 cycles at every 12 weeks in duration of 151.3 weeks)

Population: The safety analysis population (SAF) included all enrolled participants who received at least 1 dose of study medication.

PFS was defined as the time from the date of the first dose of crizotinib to first documentation of objective PD or to death on study due to any cause, whichever occurred first. If no progression or death on study was observed, or given antitumor treatment other than study drug, participants were censored on date of last on-study tumor assessment. RECIST v1.1, PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes 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 a sign of progression. Unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg n=127 Participants Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
IRR-Assessed Progression Free Survival (PFS)	15.9 Months Interval 12.9 to 24.0

SECONDARY outcome

Timeframe: From date of the first dose of crizotinib until the date of death from any cause (up to 291.9 weeks)

Population: SAF included all enrolled participants who received at least 1 dose of study medication.

OS was defined as the time from the date of the first dose of crizotinib to the date of death due to any cause. For participants still alive at the time of analysis, the OS time was censored on the last date the participants were known to be alive.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg n=127 Participants Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Overall Survival (OS)	44.2 Months Interval 32.0 to Upper limit was not estimable due to high number of participants were censored.

SECONDARY outcome

Timeframe: Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks)

Population: SAF included all enrolled participants who received at least 1 dose of study medication.

Treatment-emergent AEs :between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to crizotinib was assessed by the investigator. Treatment-related AE: any untoward medical occurrence attributed to study drug in a participant who received study drug. Serious adverse event (SAE):an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg n=127 Participants Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs, Treatment Emergent Treatment Related AEs and SAEs, Grade 3 or 4 Treatment Emergent AEs and Grade 3 or 4 Treatment Emergent Treatment Related AEs Incidence of All-Causality Adverse Events	127 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs, Treatment Emergent Treatment Related AEs and SAEs, Grade 3 or 4 Treatment Emergent AEs and Grade 3 or 4 Treatment Emergent Treatment Related AEs Incidence of All-Causality Serious Adverse Events	46 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs, Treatment Emergent Treatment Related AEs and SAEs, Grade 3 or 4 Treatment Emergent AEs and Grade 3 or 4 Treatment Emergent Treatment Related AEs Incidence of Treatment Related Adverse Events	124 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs, Treatment Emergent Treatment Related AEs and SAEs, Grade 3 or 4 Treatment Emergent AEs and Grade 3 or 4 Treatment Emergent Treatment Related AEs Incidence of Treatment Related Serious Adverse Events	11 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs, Treatment Emergent Treatment Related AEs and SAEs, Grade 3 or 4 Treatment Emergent AEs and Grade 3 or 4 Treatment Emergent Treatment Related AEs Incidence of All-Causality Grade 3-4 Adverse Event	68 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs, Treatment Emergent Treatment Related AEs and SAEs, Grade 3 or 4 Treatment Emergent AEs and Grade 3 or 4 Treatment Emergent Treatment Related AEs Incidence of Treatment Related Grade 3-4 Adverse Event	41 Participants

SECONDARY outcome

Timeframe: Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks)

Population: SAF included all enrolled participants who received at least 1 dose of study medication. Here, "number analyzed" signifies participants evaluable at specific rows.

Laboratory values included hemoglobin increased, anemia, platelet count decreased, leukocytosis, white blood cell decreased, lymphocyte count increased, lymphocyte count decreased and neutrophil count decreased. Laboratory values were defined as National Cancer Institute Common Toxicity Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) grade 3 or higher.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg n=127 Participants Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hemoglobin Increased: Baseline Grade 1 to Worst Grade 3	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 White Blood Cell Decreased: Baseline Grade 2 to Worst Grade 4	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hemoglobin Increased: Baseline Grade 0 to Worst Grade 3	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hemoglobin Increased: Baseline Grade 2 to Worst Grade 3	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Anemia: Baseline Grade 0 to Worst Grade 3	2 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Anemia: Baseline Grade 1 to Worst Grade 3	1 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Anemia: Baseline Grade 2 to Worst Grade 3	5 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Anemia: Baseline Grade 0 to Worst Grade 4	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Anemia: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Anemia: Baseline Grade 2 to Worst Grade 4	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Platelet Count Decreased: Baseline Grade 0 to Worst Grade 3	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Platelet Count Decreased: Baseline Grade 1 to Worst Grade 3	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Platelet Count Decreased: Baseline Grade 2 to Worst Grade 3	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Platelet Count Decreased: Baseline Grade 0 to Worst Grade 4	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Platelet Count Decreased: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Platelet Count Decreased: Baseline Grade 2 to Worst Grade 4	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Leukocytosis: Baseline Grade 0 to Worst Grade 3	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Leukocytosis: Baseline Grade 0 to Worst Grade 4	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 White Blood Cell Decreased: Baseline Grade 0 to Worst Grade 3	3 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 White Blood Cell Decreased: Baseline Grade 1 to Worst Grade 3	1 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 White Blood Cell Decreased: Baseline Grade 2 to Worst Grade 3	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 White Blood Cell Decreased: Baseline Grade 0 to Worst Grade 4	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 White Blood Cell Decreased: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Lymphocyte Count Increased: Baseline Grade 0 to Worst Grade 3	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Lymphocyte Count Increased: Baseline Grade 2 to Worst Grade 3	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Lymphocyte Count Decreased: Baseline Grade 0 to Worst Grade 3	4 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Lymphocyte Count Decreased: Baseline Grade 1 to Worst Grade 3	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Lymphocyte Count Decreased: Baseline Grade 2 to Worst Grade 3	2 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Lymphocyte Count Decreased: Baseline Grade 0 to Worst Grade 4	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Lymphocyte Count Decreased: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Lymphocyte Count Decreased: Baseline Grade 2 to Worst Grade 4	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Neutrophil Count Decreased: Baseline Grade 0 to Worst Grade 3	7 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Neutrophil Count Decreased: Baseline Grade 1 to Worst Grade 3	1 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Neutrophil Count Decreased: Baseline Grade 2 to Worst Grade 3	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Neutrophil Count Decreased: Baseline Grade 0 to Worst Grade 4	4 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Neutrophil Count Decreased: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift in Hematology Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Neutrophil Count Decreased: Baseline Grade 2 to Worst Grade 4	0 Participants

SECONDARY outcome

Timeframe: Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks)

Population: SAF included all enrolled participants who received at least one dose of study medication. Here, "number analyzed" signifies participants evaluable at specific rows.

Laboratory values included blood bilirubin increased, alanine aminotransferase increased, aspartate aminotransferase increased, alkaline phosphatase increased, hypoalbuminemia, hypernatremia, hyponatremia, hyperkalemia, hypokalemia, hypercalcemia, hypocalcemia, hypophosphatemia, Creatinine increased, hyperuricemia, hypermagnesemia, hypomagnesemia, hyperglycemia and hypoglycemia. Laboratory values were defined as National Cancer Institute Common Toxicity Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) grade 3 or higher.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg n=127 Participants Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Blood Bilirubin Increased: Baseline Grade 2 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Blood Bilirubin Increased: Baseline Grade 0 to Worst Grade 3	1 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Blood Bilirubin Increased: Baseline Grade 1 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Blood Bilirubin Increased: Baseline Grade 2 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Blood Bilirubin Increased: Baseline Grade 0 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Blood Bilirubin Increased: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Alanine Aminotransferase Increased: Baseline Grade 0 to Worst Grade 3	4 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Alanine Aminotransferase Increased: Baseline Grade 1 to Worst Grade 3	1 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Alanine Aminotransferase Increased: Baseline Grade 2 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Alanine Aminotransferase Increased: Baseline Grade 0 to Worst Grade 4	4 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Alanine Aminotransferase Increased: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Alanine Aminotransferase Increased: Baseline Grade 2 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Aspartate Aminotransferase Increased : Baseline Grade 0 to Worst Grade 3	2 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Aspartate Aminotransferase Increased : Baseline Grade 1 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Aspartate Aminotransferase Increased : Baseline Grade 2 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Aspartate Aminotransferase Increased : Baseline Grade 0 to Worst Grade 4	4 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Aspartate Aminotransferase Increased : Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Aspartate Aminotransferase Increased : Baseline Grade 2 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Alkaline Phosphatase Increased : Baseline Grade 0 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Alkaline Phosphatase Increased : Baseline Grade 1 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Alkaline Phosphatase Increased : Baseline Grade 2 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Alkaline Phosphatase Increased : Baseline Grade 0 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Alkaline Phosphatase Increased : Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Alkaline Phosphatase Increased : Baseline Grade 2 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypoalbuminemia: Baseline Grade 0 to Worst Grade 3	1 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypoalbuminemia: Baseline Grade 1 to Worst Grade 3	1 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypoalbuminemia: Baseline Grade 2 to Worst Grade 3	1 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypoalbuminemia: Baseline Grade 0 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypoalbuminemia: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypoalbuminemia: Baseline Grade 2 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypernatremia: Baseline Grade 0 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypernatremia: Baseline Grade 1 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypernatremia: Baseline Grade 2 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypernatremia: Baseline Grade 0 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypernatremia: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypernatremia: Baseline Grade 2 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyponatremia: Baseline Grade 0 to Worst Grade 3	8 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyponatremia: Baseline Grade 1 to Worst Grade 3	4 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyponatremia: Baseline Grade 0 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyponatremia: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyperkalemia: Baseline Grade 0 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyperkalemia: Baseline Grade 1 to Worst Grade 3	1 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyperkalemia: Baseline Grade 2 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyperkalemia: Baseline Grade 0 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyperkalemia: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyperkalemia: Baseline Grade 2 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypokalemia: Baseline Grade 0 to Worst Grade 3	5 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypokalemia: Baseline Grade 1 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypokalemia: Baseline Grade 2 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypokalemia: Baseline Grade 0 to Worst Grade 4	1 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypokalemia: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypokalemia: Baseline Grade 2 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypercalcemia: Baseline Grade 0 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypercalcemia: Baseline Grade 1 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypercalcemia: Baseline Grade 2 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypercalcemia: Baseline Grade 0 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypercalcemia: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypercalcemia: Baseline Grade 2 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypocalcemia: Baseline Grade 0 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypocalcemia: Baseline Grade 1 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypocalcemia: Baseline Grade 2 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypocalcemia: Baseline Grade 0 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypocalcemia: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypocalcemia: Baseline Grade 2 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypophosphatemia: Baseline Grade 0 to Worst Grade 3	11 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypophosphatemia: Baseline Grade 1 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypophosphatemia: Baseline Grade 2 to Worst Grade 3	1 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypophosphatemia: Baseline Grade 0 to Worst Grade 4	1 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypophosphatemia: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypophosphatemia: Baseline Grade 2 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Creatinine Increased: Baseline Grade 0 to Worst Grade 3	1 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Creatinine Increased: Baseline Grade 1 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Creatinine Increased: Baseline Grade 2 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Creatinine Increased: Baseline Grade 0 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Creatinine Increased: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Creatinine Increased: Baseline Grade 2 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyperuricemia: Baseline Grade 0 to Worst Grade 3	33 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyperuricemia: Baseline Grade 1 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyperuricemia: Baseline Grade 0 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyperuricemia: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypermagnesemia: Baseline Grade 0 to Worst Grade 3	2 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypermagnesemia: Baseline Grade 1 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypermagnesemia: Baseline Grade 0 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypermagnesemia: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypomagnesemia: Baseline Grade 0 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypomagnesemia: Baseline Grade 1 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypomagnesemia: Baseline Grade 2 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypomagnesemia: Baseline Grade 0 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypomagnesemia: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypomagnesemia: Baseline Grade 2 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyperglycemia: Baseline Grade 0 to Worst Grade 3	1 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyperglycemia: Baseline Grade 1 to Worst Grade 3	1 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyperglycemia: Baseline Grade 2 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyperglycemia: Baseline Grade 0 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyperglycemia: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hyperglycemia: Baseline Grade 2 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypoglycemia: Baseline Grade 0 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypoglycemia: Baseline Grade 1 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypoglycemia: Baseline Grade 2 to Worst Grade 3	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypoglycemia: Baseline Grade 0 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypoglycemia: Baseline Grade 1 to Worst Grade 4	0 Participants
Number of Participants With a Shift of Chemistry Laboratory Results From Baseline Grade </=2 to Worst Grade 3 or Grade 4 Hypoglycemia: Baseline Grade 2 to Worst Grade 4	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Cycle 60

Population: Patient reported outcome (PRO)-evaluable population (PRO) included enrolled participants who received at least 1 dose of study medication and completed the assessments at baseline and with at least 1 post-baseline time point. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

The EORTC QLQ-C30 consists of 30 questions which are incorporated into 5 functional domains (physical, role, cognitive, emotional, and social); a global health status/global QOL scale; 3 symptom scales (fatigue, pain, nausea and vomiting scales); and 6 single items that assess the additional symptoms (dyspnea, appetite loss, sleep disturbance/insomnia, constipation, and diarrhea) and the perceived financial burden of treatment. All the scales and single-item scores ranged from 0 to 100, higher score is indicative of a higher response level (high score for a functional scale represents a high / healthy level of functioning; high score for the global health status / QoL represents a high QoL; a high score for a symptom scale / item represents a high level of symptomatology / problems).

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg n=26 Participants Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Scores Global Health Status	11.85 Units on a scale Standard Deviation 20.844
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Scores Physical Functioning	3.08 Units on a scale Standard Deviation 11.964
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Scores Role Functioning	-0.65 Units on a scale Standard Deviation 17.945
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Scores Emotional Functioning	10.77 Units on a scale Standard Deviation 18.146
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Scores Cognitive Functioning	3.20 Units on a scale Standard Deviation 14.159
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Scores Social Functioning	5.13 Units on a scale Standard Deviation 20.961
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Scores Fatigue	-12.30 Units on a scale Standard Deviation 20.156
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Scores Nausea and Vomiting	0.64 Units on a scale Standard Deviation 14.517
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Scores Pain	-12.18 Units on a scale Standard Deviation 16.027
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Scores Dyspnea	-6.41 Units on a scale Standard Deviation 21.124
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Scores Insomnia	-11.53 Units on a scale Standard Deviation 16.161
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Scores Appetite loss	-14.10 Units on a scale Standard Deviation 23.428
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Scores Constipation	10.26 Units on a scale Standard Deviation 27.920
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Scores Diarrhoea	1.28 Units on a scale Standard Deviation 19.937
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) Questionnaire Core 30 (QLQ-C30) Scores Financial difficulties	-21.80 Units on a scale Standard Deviation 28.199

SECONDARY outcome

Timeframe: Baseline up to Cycle 60

Population: PRO evaluable population included participants from the safety analysis population who completed the assessments at baseline and at least one post-baseline time point. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

The EORTC QLQ-LC13 consisted of 1 multi-item scale and 9 single items that assessed specific symptoms (dyspnea, cough, hemoptysis, and site-specific pain), side effects (sore mouth, dysphagia, neuropathy, and alopecia). Scores on each scale and item ranged from 0 to 100, higher score is indicative of a higher response level (a high score for a symptom scale / item represents a high level of symptomatology / problems).

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg n=26 Participants Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 Scores Dyspnea	-4.74 Units on a scale Standard Deviation 14.791
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 Scores Coughing	-12.82 Units on a scale Standard Deviation 29.936
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 Scores Hemoptysis	-5.12 Units on a scale Standard Deviation 12.253
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 Scores Sore mouth	-1.28 Units on a scale Standard Deviation 14.844
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 Scores Dysphagia	0.00 Units on a scale Standard Deviation 16.314
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 Scores Peripheral neuropathy	3.85 Units on a scale Standard Deviation 19.611
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 Scores Alopecia	-2.57 Units on a scale Standard Deviation 20.910
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 Scores Pain in chest	-12.82 Units on a scale Standard Deviation 21.236
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 Scores Pain in arm or shoulder	-15.37 Units on a scale Standard Deviation 23.536
Change From Baseline to Cycle 60 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 Scores Pain in other parts	-7.68 Units on a scale Standard Deviation 21.718

Adverse Events

Crizotinib 250 mg

Serious events: 46 serious events

Other events: 127 other events

Deaths: 65 deaths

Serious adverse events

Serious adverse events
Measure	Crizotinib 250 mg n=127 participants at risk Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Cardiac disorders Acute myocardial infarction	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Abdominal pain	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Disease Progression	5.5% 7/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Hepatobiliary disorders Hepatic cyst	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Hepatobiliary disorders Hepatic function abnormal	1.6% 2/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Pneumonia	7.9% 10/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Appendicitis	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Bronchiolitis	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Bronchopulmonary aspergillosis	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Cellulitis	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Empyema	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Oesophageal infection	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Urinary tract infection	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Alanine aminotransferase increased	1.6% 2/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Aspartate aminotransferase increased	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Hepatic enzyme increased	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Decreased appetite	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Malnutrition	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Headache	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Ruptured cerebral aneurysm	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Seizure	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Renal and urinary disorders Renal cyst	1.6% 2/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.4% 3/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.9% 5/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Vascular disorders Deep vein thrombosis	1.6% 2/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Vascular disorders Embolism	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Anaemia	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Bradycardia	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Eye disorders Retinal detachment	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Chronic gastritis	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Hernia	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Peripheral swelling	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Hepatobiliary disorders Drug-induced liver injury	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Hepatobiliary disorders Liver injury	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Postoperative wound infection	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Renal tuberculosis	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Tuberculosis	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Injury, poisoning and procedural complications Road traffic accident	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Hypoproteinaemia	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Arthropathy	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mediastinum neoplasm	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Dysarthria	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Epilepsy	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Renal and urinary disorders Chronic kidney disease	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.79% 1/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.

Other adverse events

Other adverse events
Measure	Crizotinib 250 mg n=127 participants at risk Participants received crizotinib 250 mg orally twice a day in a cycle of 28 days. Dose was modified by investigator if there was treatment-related toxicity. Maximum treatment exposure time was of 291.9 weeks up to final analysis date.
Blood and lymphatic system disorders Neutropenia	11.0% 14/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Anaemia	11.8% 15/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Blood and lymphatic system disorders Leukopenia	6.3% 8/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Cardiac disorders Sinus bradycardia	8.7% 11/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Eye disorders Vision blurred	19.7% 25/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Eye disorders Visual impairment	17.3% 22/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Eye disorders Diplopia	5.5% 7/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Eye disorders Photopsia	5.5% 7/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Diarrhoea	48.8% 62/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Nausea	45.7% 58/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Vomiting	39.4% 50/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Constipation	38.6% 49/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Abdominal pain upper	9.4% 12/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Abdominal pain	9.4% 12/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Stomatitis	7.9% 10/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Oedema peripheral	30.7% 39/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Fatigue	17.3% 22/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Pyrexia	18.1% 23/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Chest pain	8.7% 11/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Nasopharyngitis	22.0% 28/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Upper respiratory tract infection	17.3% 22/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Pneumonia	8.7% 11/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Infections and infestations Urinary tract infection	8.7% 11/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Alanine aminotransferase increased	56.7% 72/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Aspartate aminotransferase increased	52.8% 67/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Neutrophil count decreased	29.1% 37/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations White blood cell count decreased	23.6% 30/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood creatinine increased	22.8% 29/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Gamma-glutamyltransferase increased	14.2% 18/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood alkaline phosphate increased	11.0% 14/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Decreased appetite	21.3% 27/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Hypoproteinaemia	11.0% 14/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Hypoalbuminaemia	14.2% 18/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Back pain	16.5% 21/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Pain in extremity	12.6% 16/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Dysgeusia	13.4% 17/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Dizziness	18.1% 23/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Headache	15.7% 20/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Psychiatric disorders Insomnia	7.9% 10/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Cough	27.6% 35/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.4% 12/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Rash	13.4% 17/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Skin and subcutaneous tissue disorders Pruritis	8.7% 11/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Abdominal distension	6.3% 8/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Gastrointestinal disorders Toothache	7.9% 10/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Asthenia	7.1% 9/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Pain	7.1% 9/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
General disorders Peripheral swelling	7.1% 9/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Hepatobiliary disorders Hepatic function abnormal	7.9% 10/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood albumin decreased	13.4% 17/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Blood creatine phosphokinase increased	7.1% 9/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Protein total decreased	5.5% 7/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Investigations Weight decreased	6.3% 8/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Hypocalcaemia	7.9% 10/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Hypokalaemia	7.9% 10/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Metabolism and nutrition disorders Hyponatraemia	9.4% 12/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Arthralgia	7.9% 10/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	7.9% 10/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Hypoaesthesia	5.5% 7/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Nervous system disorders Taste disorder	6.3% 8/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
Respiratory, thoracic and mediastinal disorders Haemoptysis	5.5% 7/127 • Baseline up to 28 days after the last dose of study treatment (maximum up to 295.9 weeks) Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
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