Trial Outcomes & Findings for Crizotinib Plus Pembrolizumab In Alk-Positive Advanced Non Small Cell Lung Cancer Patients (NCT NCT02511184)

Last Updated: 2019-07-01

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

9 participants

Primary outcome timeframe

6 weeks

Results posted on

2019-07-01

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	2	7
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	2	7

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Death	1	0
Overall Study Lost to Follow-up	0	1
Overall Study Study terminated by sponsor	1	5
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Crizotinib Plus Pembrolizumab In Alk-Positive Advanced Non Small Cell Lung Cancer Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Crizotinib + Pembrolizumab n=2 Participants 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.	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab n=7 Participants 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.	Total n=9 Participants Total of all reporting groups
Age, Continuous	64.5 years STANDARD_DEVIATION 12 • n=5 Participants	56.4 years STANDARD_DEVIATION 13 • n=7 Participants	58.2 years STANDARD_DEVIATION 12.6 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized White	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 weeks

Population: 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.

Outcome measures

Outcome measures
Measure	Crizotinib + Pembrolizumab n=2 Participants 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.	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab n=7 Participants 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.
Number of Participants With Dose-limiting Toxicity (DLT)	2 Participants	2 Participants

SECONDARY outcome

Timeframe: 2 years

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

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.

Outcome measures

Outcome measures
Measure	Crizotinib + Pembrolizumab n=2 Participants 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.	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab n=7 Participants 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.
Number of Participants With Treatment-Emergent Adverse Events All-causality AE	2 Participants	7 Participants
Number of Participants With Treatment-Emergent Adverse Events All-causality SAE	2 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events Crizotinib-related AE	2 Participants	7 Participants
Number of Participants With Treatment-Emergent Adverse Events Crizotinib-related SAE	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events Pembrolizumab-related AE	2 Participants	6 Participants
Number of Participants With Treatment-Emergent Adverse Events Pembrolizumab-related SAE	2 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events Grade 1 all-causality AE	0 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events Grade 2 all-causality AE	0 Participants	2 Participants
Number of Participants With Treatment-Emergent Adverse Events Grade 3 all-causality AE	0 Participants	4 Participants
Number of Participants With Treatment-Emergent Adverse Events Grade 4 all-causality AE	1 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events Grade 5 all-causality AE	1 Participants	0 Participants

SECONDARY outcome

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

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

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.

Outcome measures

Outcome measures
Measure	Crizotinib + Pembrolizumab n=2 Participants 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.	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab n=7 Participants 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.
Objective Response Rate (ORR)	50 percentage of participants	57.1 percentage of participants

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Crizotinib + Pembrolizumab n=1 Participants 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.	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab n=4 Participants 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.
Duration of Response	85 days Interval 85.0 to 85.0	242 days Interval 126.0 to 339.0

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Crizotinib + Pembrolizumab n=1 Participants 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.	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab n=4 Participants 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.
Time to Tumor Response	57 days Interval 57.0 to 57.0	83 days Interval 77.0 to 87.0

SECONDARY outcome

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

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

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.

Outcome measures

Outcome measures
Measure	Crizotinib + Pembrolizumab n=2 Participants 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.	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab n=7 Participants 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.
Progression Free Survival	131.5 days Interval 122.0 to 141.0	211 days Interval 1.0 to 418.0

SECONDARY outcome

Timeframe: Month 6, Month 12, and Month 18

Population: Data were not collected.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

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

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.

Outcome measures

Outcome measures
Measure	Crizotinib + Pembrolizumab n=2 Participants 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.	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab n=7 Participants 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.
Overall Survival	452.5 days Interval 122.0 to 783.0	428 days Interval 272.0 to 730.0

SECONDARY outcome

Timeframe: Month 12 and Month 18

Population: Data were not collected.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

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

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.

Outcome measures

Outcome measures
Measure	Crizotinib + Pembrolizumab n=2 Participants 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.	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab n=7 Participants 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.
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 Anemia	0 Participants	0 Participants
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 Hemoglobin increased	0 Participants	0 Participants
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 Lymphocyte count increased	0 Participants	0 Participants
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 Lymphopenia	0 Participants	2 Participants
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 Absolute neutrophils	0 Participants	0 Participants
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 platelets	0 Participants	0 Participants
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 White blood cells	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 2 years

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

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.

Outcome measures

Outcome measures
Measure	Crizotinib + Pembrolizumab n=2 Participants 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.	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab n=7 Participants 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.
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 Alanine aminotransferase	1 Participants	3 Participants
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 Alkaline phosphatase	0 Participants	0 Participants
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 Aspartate aminotransferase	1 Participants	1 Participants
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 Total bilirubin	0 Participants	0 Participants
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 Creatine kinase	0 Participants	0 Participants
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 Creatinine	0 Participants	0 Participants
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 Gamma-glutamyl transferase	0 Participants	0 Participants
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 Hypercalcemia	0 Participants	0 Participants
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 Hyperglycemia	0 Participants	1 Participants
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 Hyperkalemia	0 Participants	0 Participants
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 Hypermagnesemia	0 Participants	0 Participants
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 Hypernatremia	0 Participants	0 Participants
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 Hypoalbuminemia	0 Participants	0 Participants
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 Hypocalcemia	0 Participants	0 Participants
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 Hypoglycemia	0 Participants	0 Participants
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 Hypokalemia	0 Participants	0 Participants
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 Hypomagnesemia	0 Participants	0 Participants
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 Hyponatremia	1 Participants	1 Participants
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 Hypophosphatemia	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 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)

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

Outcome measures

Outcome measures
Measure	Crizotinib + Pembrolizumab n=2 Participants 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.	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.
Plasma Concentration Summary of Crizotinib for "Crizotinib + Pembrolizumab" Group Day 1 of Cycle 1: pre-dose	0 nanograms/milliliter (ng/mL) Interval 0.0 to 0.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib + Pembrolizumab" Group Day 1 of Cycle 2: pre-dose	379 nanograms/milliliter (ng/mL) Interval 379.0 to 379.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib + Pembrolizumab" Group Day 1 of Cycle 4: pre-dose	147 nanograms/milliliter (ng/mL) Interval 147.0 to 147.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: pre-dose	235 nanograms/milliliter (ng/mL) Interval 235.0 to 235.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib + Pembrolizumab" Group Day 1 of Cycle 8: pre-dose	257 nanograms/milliliter (ng/mL) Interval 257.0 to 257.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib + Pembrolizumab" Group End of treatment	166.04 nanograms/milliliter (ng/mL) Interval 8.08 to 324.0	—

SECONDARY outcome

Timeframe: 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)

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

Outcome measures

Outcome measures
Measure	Crizotinib + Pembrolizumab n=7 Participants 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.	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.
Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 15 of monotherapy: pre-dose	273 ng/mL Interval 79.9 to 531.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 15 of monotherapy: 1 hour post-dose	262.5 ng/mL Interval 191.0 to 300.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 15 of monotherapy: 2 hours post-dose	345 ng/mL Interval 159.0 to 455.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 15 of monotherapy: 4 hours post-dose	331 ng/mL Interval 133.0 to 375.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 15 of monotherapy: 6 hours post-dose	278 ng/mL Interval 115.0 to 373.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 15 of monotherapy: 8 hours post-dose	294.5 ng/mL Interval 129.0 to 382.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 1: pre-dose	272.5 ng/mL Interval 176.0 to 337.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 2: pre-dose	131 ng/mL Interval 0.842 to 249.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 4: pre-dose	194.5 ng/mL Interval 37.5 to 352.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: pre-dose	249 ng/mL Interval 175.0 to 311.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: 1 hour post-dose	272 ng/mL Interval 184.0 to 281.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: 2 hours post-dose	274 ng/mL Interval 194.0 to 497.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: 4 hours post-dose	317 ng/mL Interval 198.0 to 450.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: 6 hours post-dose	301 ng/mL Interval 172.0 to 369.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: 8 hours post-dose	229.5 ng/mL Interval 173.0 to 367.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 8: pre-dose	244.5 ng/mL Interval 159.0 to 285.0	—
Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group End of treatment	24.65 ng/mL Interval 0.65 to 489.0	—

SECONDARY outcome

Timeframe: 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)

Population: Data were not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: Data were not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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)

Population: Data were not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: Data were not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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)

Population: Data were not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: Data were not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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)

Population: Data were not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: Data were not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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)

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

PF-06260182 is a metabolite of crizotinib.

Outcome measures

Outcome measures
Measure	Crizotinib + Pembrolizumab n=2 Participants 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.	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.
Plasma Concentration Summary of PF-06260182 for "Crizotinib + Pembrolizumab" Group Day 1 of Cycle 1: pre-dose	0 ng/mL Interval 0.0 to 0.0	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib + Pembrolizumab" Group Day 1 of Cycle 2: pre-dose	182 ng/mL Interval 182.0 to 182.0	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib + Pembrolizumab" Group Day 1 of Cycle 4: pre-dose	46.4 ng/mL Interval 46.4 to 46.4	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: pre-dose	99.1 ng/mL Interval 99.1 to 99.1	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib + Pembrolizumab" Group Day 1 of Cycle 8: pre-dose	67 ng/mL Interval 67.0 to 67.0	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib + Pembrolizumab" Group End of treatment	56.58 ng/mL Interval 2.16 to 111.0	—

SECONDARY outcome

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

PF-06260182 is a metabolite of crizotinib.

Outcome measures

Outcome measures
Measure	Crizotinib + Pembrolizumab n=7 Participants 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.	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.
Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 15 of monotherapy: pre-dose	91.35 ng/mL Interval 28.4 to 148.0	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 15 of monotherapy: 1 hour post-dose	74.15 ng/mL Interval 46.8 to 93.9	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 15 of monotherapy: 2 hours post-dose	84.3 ng/mL Interval 52.3 to 141.0	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 15 of monotherapy: 4 hours post-dose	107 ng/mL Interval 53.3 to 117.0	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 15 of monotherapy: 6 hours post-dose	91.85 ng/mL Interval 45.8 to 105.0	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 15 of monotherapy: 8 hours post-dose	84.5 ng/mL Interval 42.5 to 129.0	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 1: pre-dose	83.2 ng/mL Interval 40.3 to 107.0	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 2: pre-dose	21.6 ng/mL Interval 0.0 to 65.1	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 4: pre-dose	61.3 ng/mL Interval 8.55 to 98.3	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: pre-dose	74.5 ng/mL Interval 30.1 to 94.1	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: 1 hour post-dose	69.8 ng/mL Interval 30.8 to 80.6	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: 2 hours post-dose	65.8 ng/mL Interval 40.8 to 144.0	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: 4 hours post-dose	73.3 ng/mL Interval 31.4 to 158.0	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: 6 hours post-dose	77.7 ng/mL Interval 38.2 to 139.0	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: 8 hours post-dose	60.6 ng/mL Interval 38.4 to 111.0	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 8: pre-dose	62.75 ng/mL Interval 32.1 to 83.9	—
Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group End of treatment	2.75 ng/mL Interval 0.0 to 112.0	—

SECONDARY outcome

Timeframe: 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)

Population: Data were not collected.

PF-06260182 is a metabolite of crizotinib.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: Data were not collected.

PF-06260182 is a metabolite of crizotinib.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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)

Population: Data were not collected.

PF-06260182 is a metabolite of crizotinib.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: Data were not collected.

PF-06260182 is a metabolite of crizotinib.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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)

Population: Data were not collected.

PF-06260182 is a metabolite of crizotinib.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: Data were not collected.

PF-06260182 is a metabolite of crizotinib.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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)

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

PF-06260182 is a metabolite of crizotinib.

Outcome measures

Outcome measures
Measure	Crizotinib + Pembrolizumab n=2 Participants 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.	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.
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib + Pembrolizumab" Group Day 1 of Cycle 2: pre-dose	0.480 ratio Interval 0.48 to 0.48	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib + Pembrolizumab" Group Day 1 of Cycle 4: pre-dose	0.316 ratio Interval 0.316 to 0.316	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: pre-dose	0.422 ratio Interval 0.422 to 0.422	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib + Pembrolizumab" Group Day 1 of Cycle 8: pre-dose	0.261 ratio Interval 0.261 to 0.261	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib + Pembrolizumab" Group End of treatment	0.305 ratio Interval 0.267 to 0.343	—

SECONDARY outcome

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

PF-06260182 is a metabolite of crizotinib.

Outcome measures

Outcome measures
Measure	Crizotinib + Pembrolizumab n=7 Participants 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.	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.
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 15 of monotherapy: pre-dose	0.334 ratio Interval 0.274 to 0.401	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 15 of monotherapy: 1 hour post dose	0.275 ratio Interval 0.226 to 0.367	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 15 of monotherapy: 2 hours post dose	0.307 ratio Interval 0.185 to 0.365	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 15 of monotherapy: 4 hours post dose	0.321 ratio Interval 0.275 to 0.401	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 15 of monotherapy: 6 hours post dose	0.330 ratio Interval 0.268 to 0.398	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 15 of monotherapy: 8 hours post dose	0.311 ratio Interval 0.263 to 0.338	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 1: pre-dose	0.311 ratio Interval 0.229 to 0.376	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 2: pre-dose	0.217 ratio Interval 0.0 to 0.303	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 4: pre-dose	0.293 ratio Interval 0.228 to 0.355	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: pre-dose	0.258 ratio Interval 0.172 to 0.361	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: 1 hour post dose	0.249 ratio Interval 0.145 to 0.287	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: 2 hours post dose	0.239 ratio Interval 0.21 to 0.29	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: 4 hours post dose	0.231 ratio Interval 0.159 to 0.351	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: 6 hours post dose	0.258 ratio Interval 0.219 to 0.406	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 6: 8 hours post dose	0.264 ratio Interval 0.212 to 0.302	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group Day 1 of Cycle 8: pre-dose	0.244 ratio Interval 0.202 to 0.323	—
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group End of treatment	0.105 ratio Interval 0.0 to 0.229	—

SECONDARY outcome

Timeframe: 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

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

Outcome measures

Outcome measures
Measure	Crizotinib + Pembrolizumab n=2 Participants 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.	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab n=7 Participants 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.
Serum Concentration of Pembrolizumab Day 1 of Cycle 1: pre-dose	0 ng/mL Interval 0.0 to 0.0	0 ng/mL Interval 0.0 to 0.0
Serum Concentration of Pembrolizumab Day 1 of Cycle 1: end of infusion	63150 ng/mL Interval 38300.0 to 88000.0	61400 ng/mL Interval 34600.0 to 102000.0
Serum Concentration of Pembrolizumab Day 8 of Cycle 1: 120 hours post Day 1 dosing	25550 ng/mL Interval 20600.0 to 30500.0	26800 ng/mL Interval 19100.0 to 31900.0
Serum Concentration of Pembrolizumab Day 15 of Cycle 1: 336 hours post Day 1 dosing	19600 ng/mL Interval 14800.0 to 24400.0	20100 ng/mL Interval 11000.0 to 23700.0
Serum Concentration of Pembrolizumab Day 1 of Cycle 2: pre-dose	9840 ng/mL Interval 8680.0 to 11000.0	15750 ng/mL Interval 8020.0 to 19600.0
Serum Concentration of Pembrolizumab Day 1 of Cycle 4: pre-dose	—	31600 ng/mL Interval 18200.0 to 37300.0
Serum Concentration of Pembrolizumab Day 1 of Cycle 8: end of infusion	—	14300 ng/mL Interval 11700.0 to 14500.0
Serum Concentration of Pembrolizumab Day 1 of Cycle 12: pre-dose	—	99350 ng/mL Interval 85700.0 to 113000.0
Serum Concentration of Pembrolizumab Day 1 of Cycle 16: pre-dose	—	29300 ng/mL Interval 29300.0 to 29300.0
Serum Concentration of Pembrolizumab End of treatment	10800 ng/mL Interval 10800.0 to 10800.0	27500 ng/mL Interval 3370.0 to 45800.0
Serum Concentration of Pembrolizumab Day 1 of Cycle 6: pre-dose	—	37000 ng/mL Interval 28500.0 to 64000.0
Serum Concentration of Pembrolizumab Day 1 of Cycle 8: pre-dose	—	38800 ng/mL Interval 26600.0 to 64500.0

SECONDARY outcome

Timeframe: Screening

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

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%.

Outcome measures

Outcome measures
Measure	Crizotinib + Pembrolizumab n=2 Participants 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.	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab n=6 Participants 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.
Number of Participants With Programmed Death Receptor-1 Ligand-1 (PD-L1) Expression Level Meeting Pre-defined Criteria Negative	1 Participants	1 Participants
Number of Participants With Programmed Death Receptor-1 Ligand-1 (PD-L1) Expression Level Meeting Pre-defined Criteria Positive	1 Participants	3 Participants
Number of Participants With Programmed Death Receptor-1 Ligand-1 (PD-L1) Expression Level Meeting Pre-defined Criteria Strong positive	0 Participants	2 Participants

Adverse Events

Crizotinib + Pembrolizumab

Serious events: 2 serious events

Other events: 2 other events

Deaths: 1 deaths

Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Crizotinib + Pembrolizumab n=2 participants at risk 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.	Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab n=7 participants at risk 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.
Infections and infestations Pneumonia	50.0% 1/2 • Number of events 2 • 2 years 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 one participant and nonserious in another participant, or one participant may have experienced both serious and nonserious event during study.	0.00% 0/7 • 2 years 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 one participant and nonserious in another participant, or one participant may have experienced both serious and nonserious event during study.
Investigations Alanine aminotransferase increased	50.0% 1/2 • Number of events 1 • 2 years 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 one participant and nonserious in another participant, or one participant may have experienced both serious and nonserious event during study.	14.3% 1/7 • Number of events 1 • 2 years 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 one participant and nonserious in another participant, or one participant may have experienced both serious and nonserious event during study.
Investigations Aspartate aminotransferase increased	50.0% 1/2 • Number of events 1 • 2 years 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 one participant and nonserious in another participant, or one participant may have experienced both serious and nonserious event during study.	14.3% 1/7 • Number of events 1 • 2 years 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 one participant and nonserious in another participant, or one participant may have experienced both serious and nonserious event during study.
Respiratory, thoracic and mediastinal disorders Pneumonitis	50.0% 1/2 • Number of events 1 • 2 years 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 one participant and nonserious in another participant, or one participant may have experienced both serious and nonserious event during study.	0.00% 0/7 • 2 years 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 one participant and nonserious in another participant, or one participant may have experienced both serious and nonserious event during study.

Other adverse events

Additional Information

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Phone: 1-800-718-1021

Email: [email protected]

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.
Publication restrictions are in place

Restriction type: OTHER