Crizotinib Plus Pembrolizumab In Alk-Positive Advanced No... | NCT02511184

ID	Type	Description	Link
KEYNOTE 050	Other Identifier	Merck Sharp & Dohme Corp
CRIZOTINIB	Other Identifier	Alias Study Number

Name	Class
Merck Sharp & Dohme LLC	INDUSTRY

Label	Type	Description	Intervention Names
Dose finding and dose expansion phases	Experimental	Find and expand the maximum tolerated dose of crizotinib in combination with pembrolizumab 200 mg iv infusion every 3 weeks.	Drug: Crizotinib Drug: Pembrolizumab

Name	Type	Description	Arm Group Labels	Other Names
Crizotinib	Drug	To test 3 dose levels of crizotinib in combination with pembrolizumab 200 mg iv infusion every 3 weeks	Dose finding and dose expansion phases

Measure	Description	Time Frame
Number of Participants With Dose-limiting Toxicity (DLT)	Dose-limiting toxicity (DLT) was defined as any of the following adverse events (AEs) occurring in the first 2 cycles of treatment (6 weeks) which were attributable to crizotinib, pembrolizumab or both: hematologic toxicities including Grade 4 neutropenia, febrile neutropenia, Grade greater than or equal to (>=) 3 neutropenic infection, Grade >=3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; non-hematologic toxicities including Grade >=3 toxicities (non-laboratory), Grade >=3 nausea, vomiting, or diarrhea despite maximal therapy, non-hematologic Grade >=3 laboratory value if medical intervention was required to treat the participant or the abnormality led to hospitalization; inability to complete at least 80 percent of the first 2-cycle doses of crizotinib or both infusions of pembrolizumab within the DLT observation period due to treatment-related toxicity. Grade was based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) version 4.03.	6 weeks

Measure	Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events	AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causal relationship to study treatment. Treatment-emergent AEs (TEAEs) were defined as AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. Severity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35233	United States
University of Alabama at Birmingham, IDS Pharmacy

Label	URL
To obtain contact information for a study center near you, click here.	View source

ID	Title	Description
FG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 22, 2015	Dec 4, 2018

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Dose-limiting Toxicity (DLT)

Dose-limiting toxicity (DLT) was defined as any of the following adverse events (AEs) occurring in the first 2 cycles of treatment (6 weeks) which were attributable to crizotinib, pembrolizumab or both: hematologic toxicities including Grade 4 neutropenia, febrile neutropenia, Grade greater than or equal to (>=) 3 neutropenic infection, Grade >=3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; non-hematologic toxicities including Grade >=3 toxicities (non-laboratory), Grade >=3 nausea, vomiting, or diarrhea despite maximal therapy, non-hematologic Grade >=3 laboratory value if medical intervention was required to treat the participant or the abnormality led to hospitalization; inability to complete at least 80 percent of the first 2-cycle doses of crizotinib or both infusions of pembrolizumab within the DLT observation period due to treatment-related toxicity. Grade was based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) version 4.03.

DLT evaluable population included all participants enrolled in the Dose Finding Phase who received at least 1 dose of crizotinib or pembrolizumab, and either experienced DLT during the first 2 cycles, or completed the observation period for the first 2 cycles of treatment.

Posted

Count of Participants

Participants

6 weeks

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.
OG001	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG0002 OG0017

Title

Denominators

Categories

Title	Measurements
	OG0002 OG0012

Secondary

Number of Participants With Treatment-Emergent Adverse Events

AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causal relationship to study treatment. Treatment-emergent AEs (TEAEs) were defined as AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. Severity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

The safety analysis set included all enrolled participants who received at least 1 dose of crizotinib or pembrolizumab.

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.
OG001

Secondary

Objective Response Rate (ORR)

ORR refers to percentage of participants who achieved complete response (CR) or partial response (PR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. A participant achieved CR if both target and non-target lesions achieved CR, no new lesions; achieved PR if target lesions achieved CR or PR, non-target lesions were assessed as non-CR/non-progressive disease (PD) or not evaluated, and no new lesions. For target lesions, CR: complete disappearance of all target lesions; PR: >= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. For non-target lesions, CR: disappearance of all non-target lesions and normalization of tumor marker levels and all lymph nodes must be non-pathological in size; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits.

The analysis population included all treated participants who had an adequate baseline tumor assessment.

Posted

Number

percentage of participants

Baseline, Week 9 and every 6 weeks thereafter, for about 2 years

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.
OG001	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab

Secondary

Duration of Response

Duration of Response (DR) was defined as the time from first documentation of objective tumor response (CR or PR) that was subsequently confirmed, to the first documentation of objective tumor progression or to death on study due to any cause, whichever occurred first.

The analysis population included all participants who achieved complete response or partial response.

Posted

Median

Full Range

days

Baseline, Week 9 and every 6 weeks thereafter, for about 2 years

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.
OG001	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Secondary

Time to Tumor Response

Time to Tumor Response (TTR) was defined as the time from the first dose of crizotinib or pembrolizumab to the first documentation of objective tumor response (CR or PR) that was subsequently confirmed.

The analysis population included all participants who achieved complete response or partial response.

Posted

Median

Full Range

days

Baseline, Week 9 and every 6 weeks thereafter, for about 2 years

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.
OG001	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Secondary

Progression Free Survival

Progression Free Survival (PFS) was defined as the time from the first dose of crizotinib or pembrolizumab to the first documentation of objective tumor progression or death on-study due to any cause, whichever occurred first. For participants who did not have documented objective progression during the study or were alive at last contact, the date of last contact was used.

The analysis population included all treated participants who had an adequate baseline tumor assessment.

Posted

Median

Full Range

days

Baseline, Week 9 and every 6 weeks thereafter, for about 2 years

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.
OG001	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Secondary

6-Month, 12-Month and 18-Month Progression Free Survival Probabilities

PFS probabilities were defined as the probability of being alive and progression free at 6, 12 and 18 months after the date of first dose based on the Kaplan Meier estimate.

Data were not collected.

Posted

Month 6, Month 12, and Month 18

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.
OG001	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts

Secondary

Overall Survival

Overall Survival (OS) was defined as the time from the first dose of crizotinib or pembrolizumab to the date of death due to any cause. For participants who were alive at last contact, the date of last contact was used.

The analysis population included all treated participants who had an adequate baseline tumor assessment.

Posted

Median

Full Range

days

Day 1 to end of study (for about 2 years)

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.
OG001	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Secondary

12-Month and 18-Month Overall Survival Probabilities

OS probabilities were defined as the probability of being alive at 12 and 18 months after the date of first dose based on the Kaplan Meier estimate.

Data were not collected.

Posted

Month 12 and Month 18

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.
OG001	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants

Secondary

Number of Participants With Maximum Grade in Laboratory Hematology Test Shifting From Grade 0, 1 or 2 at Baseline to Grade 3 or 4 During Treatment

Hematology evaluation included hemoglobin, platelets, white blood cell, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, and absolute basophils. Hematology test results were graded by NCI CTCAE version 4.03.

The safety analysis set included all enrolled participants who received at least 1 dose of crizotinib or pembrolizumab.

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.
OG001	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Secondary

Number of Participants With Maximum Grade in Laboratory Chemistry Test Shifting From Grade 0, 1 or 2 at Baseline to Grade 3 or 4 During Treatment

Chemistry evaluation included alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen or urea, creatinine, uric acid, glucose, albumin, phosphorous or phosphate, thyroid function tests including thyroid-stimulating hormone, T3 and free T4. Chemistry test results were graded by NCI CTCAE version 4.03.

The safety analysis set included all enrolled participants who received at least 1 dose of crizotinib or pembrolizumab.

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.
OG001	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Secondary

Plasma Concentration Summary of Crizotinib for "Crizotinib + Pembrolizumab" Group

The analysis population included all treated participants who had at least 1 crizotinib concentration measurement.

Posted

Median

Full Range

nanograms/milliliter (ng/mL)

Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

The analysis population included all treated participants who had at least 1 crizotinib concentration measurement.

Posted

Median

Full Range

ng/mL

Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment)

ID	Title	Description
OG000	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Time to Maximum Plasma Concentration (Tmax) of Crizotinib for "Crizotinib + Pembrolizumab" Group

Data were not collected.

Posted

Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Time to Maximum Plasma Concentration (Tmax) of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

Data were not collected.

Posted

ID	Title	Description
OG000	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Area Under the Plasma Concentration Time Curve From 0 to 8 Hours (AUC0-8) of Crizotinib for "Crizotinib + Pembrolizumab" Group

Data were not collected.

Posted

Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Area Under the Plasma Concentration Time Curve From 0 to 8 Hours (AUC0-8) of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

Data were not collected.

Posted

ID	Title	Description
OG000	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of Crizotinib for "Crizotinib + Pembrolizumab" Group

Data were not collected.

Posted

Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

Data were not collected.

Posted

ID	Title	Description
OG000	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Apparent Plasma Clearance (CL/F) of Crizotinib for "Crizotinib + Pembrolizumab" Group

Data were not collected.

Posted

Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Apparent Plasma Clearance (CL/F) of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

Data were not collected.

Posted

ID	Title	Description
OG000	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Plasma Concentration Summary of PF-06260182 for "Crizotinib + Pembrolizumab" Group

PF-06260182 is a metabolite of crizotinib.

The analysis population included all treated participants who had at least 1 PF-06260182 concentration measurement.

Posted

Median

Full Range

ng/mL

Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

PF-06260182 is a metabolite of crizotinib.

The analysis population included all treated participants who had at least 1 PF-06260182 concentration measurement.

Posted

Median

Full Range

ng/mL

ID	Title	Description
OG000	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Time to Maximum Plasma Concentration (Tmax) of PF-06260182 for "Crizotinib + Pembrolizumab" Group

PF-06260182 is a metabolite of crizotinib.

Data were not collected.

Posted

Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Time to Maximum Plasma Concentration (Tmax) of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

PF-06260182 is a metabolite of crizotinib.

Data were not collected.

Posted

ID	Title	Description
OG000	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of PF-06260182 for "Crizotinib + Pembrolizumab" Group

PF-06260182 is a metabolite of crizotinib.

Data were not collected.

Posted

Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

PF-06260182 is a metabolite of crizotinib.

Data were not collected.

Posted

ID	Title	Description
OG000	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Metabolite (PF-06260182) to Parent (Crizotinib) AUCtau Ratio for "Crizotinib + Pembrolizumab" Group

PF-06260182 is a metabolite of crizotinib.

Data were not collected.

Posted

Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Metabolite (PF-06260182) to Parent (Crizotinib) AUCtau Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

PF-06260182 is a metabolite of crizotinib.

Data were not collected.

Posted

ID	Title	Description
OG000	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib + Pembrolizumab" Group

PF-06260182 is a metabolite of crizotinib.

The analysis population included all treated participants who had at least 1 PF-06260182 concentration measurement and at least 1 crizotinib concentration measurement.

Posted

Median

Full Range

ratio

Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment)

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group

PF-06260182 is a metabolite of crizotinib.

The analysis population included all participants who had at least 1 PF-06260182 concentration measurement and at least 1 crizotinib concentration measurement.

Posted

Median

Full Range

ratio

ID	Title	Description
OG000	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units	Counts
Participants	OG000

Secondary

Serum Concentration of Pembrolizumab

The analysis population included all treated participants who had at least 1 pembrolizumab concentration measurement.

Posted

Median

Full Range

ng/mL

Prior to and at end of pembrolizumab infusion, 120 hours and 336 hours post Day 1 dosing of Cycle 1; pre-dose on Day 1 of Cycles 2, 4,6, 8, 12 and 16; end of Day 1 dosing of Cycle 8; End of Treatment visit

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.
OG001	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Units

Secondary

Number of Participants With Programmed Death Receptor-1 Ligand-1 (PD-L1) Expression Level Meeting Pre-defined Criteria

Archived formalin-fixed, paraffin-embedded tumor issue block was collected at screening. PD-L1 assessment was performed using immunohistochemistry. A sample was considered negative if tumor proportion score was less than 1%; positive if tumor proportion score was greater than or equal to 1%; strong positive if tumor proportion score was greater than or equal to 50%.

The analysis population included all participants who had evaluable PD-L1 measurements.

Posted

Count of Participants

Participants

Screening

ID	Title	Description
OG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.
OG001	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0012 events1 affected7 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk
Tachycardia	Cardiac disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk
Diplopia	Eye disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Dry eye	Eye disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Visual impairment	Eye disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0013 events3 affected7 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Constipation	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0014 events3 affected7 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0004 events1 affected2 at risk EG0018 events5 affected7 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0012 events1 affected7 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Flatulence	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Nausea	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0003 events1 affected2 at risk EG0017 events5 affected7 at risk
Vomiting	Gastrointestinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected7 at risk
Chest discomfort	General disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Chills	General disorders	MedDRA 20.1	Non-systematic Assessment	EG0002 events1 affected2 at risk EG0012 events2 affected7 at risk
Fatigue	General disorders	MedDRA 20.1	Non-systematic Assessment	EG0005 events1 affected2 at risk EG0012 events2 affected7 at risk
Influenza like illness	General disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected7 at risk
Oedema peripheral	General disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected7 at risk
Peripheral swelling	General disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Pyrexia	General disorders	MedDRA 20.1	Non-systematic Assessment	EG0005 events2 affected2 at risk EG0010 events0 affected7 at risk
Biliary dilatation	Hepatobiliary disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Oral candidiasis	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk
Sinusitis	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Skin infection	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Urinary tract infection	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0013 events2 affected7 at risk
Alanine aminotransferase increased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0007 events2 affected2 at risk EG00112 events6 affected7 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0006 events2 affected2 at risk EG0018 events5 affected7 at risk
Blood albumin decreased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0013 events3 affected7 at risk
Blood creatinine increased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Blood phosphorus decreased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Blood potassium increased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Blood sodium decreased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk
Lymphocyte count decreased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0014 events2 affected7 at risk
Weight decreased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Weight increased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0002 events1 affected2 at risk EG0010 events0 affected7 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 20.1	Non-systematic Assessment	EG0002 events1 affected2 at risk EG0011 events1 affected7 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk
Fluid retention	Metabolism and nutrition disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0012 events2 affected7 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0017 events2 affected7 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected7 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0012 events1 affected7 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0011 events1 affected7 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0016 events2 affected7 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Arthropathy	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected7 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected7 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected7 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Amnesia	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Dizziness	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Dysgeusia	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG0002 events2 affected2 at risk EG0011 events1 affected7 at risk
Headache	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0013 events3 affected7 at risk
Paraesthesia	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Tremor	Nervous system disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Insomnia	Psychiatric disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0013 events3 affected7 at risk
Irritability	Psychiatric disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk
Mood swings	Psychiatric disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Dysuria	Renal and urinary disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0011 events1 affected7 at risk
Laryngeal inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0012 events2 affected7 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk
Pulmonary pain	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0012 events1 affected7 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0011 events1 affected7 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 20.1	Non-systematic Assessment	EG0000 events0 affected2 at risk EG0015 events2 affected7 at risk
Flushing	Vascular disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk
Hypertension	Vascular disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0012 events1 affected7 at risk
Hypotension	Vascular disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk

ID	Term
D008175	Lung Neoplasms
D002289	Carcinoma, Non-Small-Cell Lung

ID	Term
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms

ID	Term
D010880	Piperidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D000631	Aminopyridines
D011725	Pyridines

ID	Title	Description
BG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.
BG001	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Crizotinib + Pembrolizumab	Participants were administered combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.	1	2	2	2	2	2
EG001	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab	Participants were administered monotherapy of crizotinib (250 mg capsule orally, twice daily) for 3 weeks, and if tolerated, followed by combination therapy of crizotinib (250 mg capsule orally, twice daily) and pembrolizumab (200 mg via 30-minute intravenous infusion, every 3 weeks) until disease progression and no clinical benefit, or unacceptable toxicity, death, or consent withdrawal, whichever occurred first.	0	7	1	7	7	7

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pneumonia	Infections and infestations	MedDRA 20.1	Non-systematic Assessment	EG0002 events1 affected2 at risk EG0010 events0 affected7 at risk
Alanine aminotransferase increased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0011 events1 affected7 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0011 events1 affected7 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Non-systematic Assessment	EG0001 events1 affected2 at risk EG0010 events0 affected7 at risk