ALK-positive Advanced NSCLC
Conditions
Keywords
crizotinib, pembrolizumab, ALK-positive NSCLC, Lung Cancer, ALK-translocated NSCLC, Non Small Cell Lung Cancer
Brief summary
The purpose of this study has 2 phases, a Dose Finding Phase will determine the maximum tolerated dose . The Dose Expansion Phase will explore the safety, tolerability, and anti-tumor activity of the combination.
Detailed description
The patients will be screened for up to 28 days before they start treatment to determine if they meet eligibility criteria. The screening procedures will include physical examination, blood work and radiological scans. In the dose finding phase, patients who meet eligibility criteria will receive crizotinib at the dose level assigned that will be taken on daily basis and pembrolizumab 200 mg intravenous infusion every 3 weeks. Once a Crizotinib dose level is decided, the dose expansion cohort will start enrolling patients who meet eligibility criteria. All patients will be followed up every three weeks. Blood samples will be drawn to test for safety and tumor activities and radiological scans will be performed on certain timepoints to determine the antitumor activities. There will be a quality of life questionnaire administered at certain time points during the study. The study will have a quality assurance plan that addresses data validation and registry procedures. There is a plan to visit the investigator site for routine monitoring and auditing. The team will conduct source data verification to assess the accuracy, completeness, or representativeness of registry data by comparing the data to external data sources (e.g., medical records, paper or electronic case report forms, or interactive voice response systems). The study will also include a statistical analysis plan describing the analytical principles and statistical techniques to be employed in order to address the primary and secondary objectives of this study, as specified in the study protocol or statistical plan.
Interventions
DRUGCrizotinib
To test 3 dose levels of crizotinib in combination with pembrolizumab 200 mg iv infusion every 3 weeks
DRUGPembrolizumab
To test pembrolizumab at 200 mg every 3 weeks in combination with crizotinib at 3 dose levels.
Sponsors
Merck Sharp & Dohme LLC
Pfizer
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically proved diagnosis of locally advanced recurrent or metastatic non-squamous NSCLC that is not suitable for local curative treatment. * Alk-positive NSCLC as determined by a test that is approved or validated for use as a companion diagnostic test. * No prior systemic therapy for metastatic disease. * Adjuvant chemotherapy more than 12 months prior to study enrollment. * Measurable disease as per RECIST 1.1 * ECOG PS 0 or 1.
Exclusion criteria
* Prior exposure to ALK receptor tyrosine kinase inhibitor, anti-PD1, anti-PDL1 or any drug targeting T-cell checkpoint pathways. * known diagnosis of immunodeficiency or is receiving systemic steroid therapy or other form of immunosuppressive therapy within 7 days of clinical trial treatment. * Active autoimmune disease that has required systemic treatment in the past 3 months. * History of extensive disseminated interstitial fibrosis or any grade of interstitial lung disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-limiting Toxicity (DLT) | 6 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Baseline, Week 9 and every 6 weeks thereafter, for about 2 years | 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. |
| Duration of Response | Baseline, Week 9 and every 6 weeks thereafter, for about 2 years | 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. |
| Time to Tumor Response | Baseline, Week 9 and every 6 weeks thereafter, for about 2 years | 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. |
| Progression Free Survival | Baseline, Week 9 and every 6 weeks thereafter, for about 2 years | 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. |
| 6-Month, 12-Month and 18-Month Progression Free Survival Probabilities | Month 6, Month 12, and Month 18 | 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. |
| Overall Survival | Day 1 to end of study (for about 2 years) | 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. |
| 12-Month and 18-Month Overall Survival Probabilities | Month 12 and Month 18 | 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. |
| 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 | 2 years | 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. |
| 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 | 2 years | 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. |
| Plasma Concentration Summary of Crizotinib for Crizotinib + Pembrolizumab Group | 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) | — |
| Plasma Concentration Summary of Crizotinib for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | 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) | — |
| Time to Maximum Plasma Concentration (Tmax) of Crizotinib for Crizotinib + Pembrolizumab Group | 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) | — |
| Time to Maximum Plasma Concentration (Tmax) of Crizotinib for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | 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) | — |
| Area Under the Plasma Concentration Time Curve From 0 to 8 Hours (AUC0-8) of Crizotinib for Crizotinib + Pembrolizumab Group | 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) | — |
| Area Under the Plasma Concentration Time Curve From 0 to 8 Hours (AUC0-8) of Crizotinib for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | 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) | — |
| Number of Participants With Treatment-Emergent Adverse Events | 2 years | 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. |
| Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of Crizotinib for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | 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) | — |
| Apparent Plasma Clearance (CL/F) of Crizotinib for Crizotinib + Pembrolizumab Group | 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) | — |
| Apparent Plasma Clearance (CL/F) of Crizotinib for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | 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) | — |
| Plasma Concentration Summary of PF-06260182 for Crizotinib + Pembrolizumab Group | 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) | PF-06260182 is a metabolite of crizotinib. |
| Plasma Concentration Summary of PF-06260182 for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | 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) | PF-06260182 is a metabolite of crizotinib. |
| Time to Maximum Plasma Concentration (Tmax) of PF-06260182 for Crizotinib + Pembrolizumab Group | 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) | PF-06260182 is a metabolite of crizotinib. |
| Time to Maximum Plasma Concentration (Tmax) of PF-06260182 for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | 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) | PF-06260182 is a metabolite of crizotinib. |
| Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of PF-06260182 for Crizotinib + Pembrolizumab Group | 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) | PF-06260182 is a metabolite of crizotinib. |
| Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of PF-06260182 for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | 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) | PF-06260182 is a metabolite of crizotinib. |
| Metabolite (PF-06260182) to Parent (Crizotinib) AUCtau Ratio for Crizotinib + Pembrolizumab Group | 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) | PF-06260182 is a metabolite of crizotinib. |
| Metabolite (PF-06260182) to Parent (Crizotinib) AUCtau Ratio for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | 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) | PF-06260182 is a metabolite of crizotinib. |
| Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for Crizotinib + Pembrolizumab Group | 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) | PF-06260182 is a metabolite of crizotinib. |
| Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | 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) | PF-06260182 is a metabolite of crizotinib. |
| Serum Concentration of Pembrolizumab | 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 | — |
| Number of Participants With Programmed Death Receptor-1 Ligand-1 (PD-L1) Expression Level Meeting Pre-defined Criteria | Screening | 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%. |
| Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of Crizotinib for Crizotinib + Pembrolizumab Group | 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) | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 2 |
| 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. | 7 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 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
| Characteristic | Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Total | Crizotinib + Pembrolizumab |
|---|---|---|---|
| Age, Continuous | 56.4 years STANDARD_DEVIATION 13 | 58.2 years STANDARD_DEVIATION 12.6 | 64.5 years STANDARD_DEVIATION 12 |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 5 Participants | 7 Participants | 2 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 2 | 0 / 7 |
| other Total, other adverse events | 2 / 2 | 7 / 7 |
| serious Total, serious adverse events | 2 / 2 | 1 / 7 |
Outcome results
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Crizotinib + Pembrolizumab | Number of Participants With Dose-limiting Toxicity (DLT) | 2 Participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Number of Participants With Dose-limiting Toxicity (DLT) | 2 Participants |
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.
Time frame: Month 12 and Month 18
Population: Data were not collected.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | 12-Month and 18-Month Overall Survival Probabilities | 12-month | — |
| Unknown | 12-Month and 18-Month Overall Survival Probabilities | 18-month | — |
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.
Time frame: Month 6, Month 12, and Month 18
Population: Data were not collected.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | 6-Month, 12-Month and 18-Month Progression Free Survival Probabilities | 6-month | — |
| Unknown | 6-Month, 12-Month and 18-Month Progression Free Survival Probabilities | 12-month | — |
| Unknown | 6-Month, 12-Month and 18-Month Progression Free Survival Probabilities | 18-month | — |
Secondary
Apparent Plasma Clearance (CL/F) of Crizotinib for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group
Time frame: 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: Data were not collected.
Secondary
Apparent Plasma Clearance (CL/F) of Crizotinib for Crizotinib + Pembrolizumab Group
Time frame: 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.
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
Time frame: 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: Data were not collected.
Secondary
Area Under the Plasma Concentration Time Curve From 0 to 8 Hours (AUC0-8) of Crizotinib for Crizotinib + Pembrolizumab Group
Time frame: 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.
Secondary
Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of Crizotinib for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group
Time frame: 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: Data were not collected.
Secondary
Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of Crizotinib for Crizotinib + Pembrolizumab Group
Time frame: 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.
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.
Time frame: 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: Data were not collected.
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.
Time frame: 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.
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Crizotinib + Pembrolizumab | Duration of Response | 85 days |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Duration of Response | 242 days |
Secondary
Metabolite (PF-06260182) to Parent (Crizotinib) AUCtau Ratio for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group
PF-06260182 is a metabolite of crizotinib.
Time frame: 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: Data were not collected.
Secondary
Metabolite (PF-06260182) to Parent (Crizotinib) AUCtau Ratio for Crizotinib + Pembrolizumab Group
PF-06260182 is a metabolite of crizotinib.
Time frame: 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.
Secondary
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group
PF-06260182 is a metabolite of crizotinib.
Time frame: 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 participants who had at least 1 PF-06260182 concentration measurement and at least 1 crizotinib concentration measurement.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | End of treatment | 0.105 ratio |
Secondary
Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for Crizotinib + Pembrolizumab Group
PF-06260182 is a metabolite of crizotinib.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Crizotinib + Pembrolizumab | Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for Crizotinib + Pembrolizumab Group | Day 1 of Cycle 2: pre-dose | 0.480 ratio |
| Crizotinib + Pembrolizumab | Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for Crizotinib + Pembrolizumab Group | Day 1 of Cycle 4: pre-dose | 0.316 ratio |
| Crizotinib + Pembrolizumab | Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for Crizotinib + Pembrolizumab Group | Day 1 of Cycle 6: pre-dose | 0.422 ratio |
| Crizotinib + Pembrolizumab | Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for Crizotinib + Pembrolizumab Group | Day 1 of Cycle 8: pre-dose | 0.261 ratio |
| Crizotinib + Pembrolizumab | Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for Crizotinib + Pembrolizumab Group | End of treatment | 0.305 ratio |
| Unknown | Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for Crizotinib + Pembrolizumab Group | Day 1 of Cycle 1: pre-dose | — ratio |
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.
Time frame: 2 years
Population: The safety analysis set included all enrolled participants who received at least 1 dose of crizotinib or pembrolizumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 | 1 Participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 | 1 Participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 | 3 Participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
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.
Time frame: 2 years
Population: The safety analysis set included all enrolled participants who received at least 1 dose of crizotinib or pembrolizumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 | 2 Participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | 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 |
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%.
Time frame: Screening
Population: The analysis population included all participants who had evaluable PD-L1 measurements.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Crizotinib + Pembrolizumab | Number of Participants With Programmed Death Receptor-1 Ligand-1 (PD-L1) Expression Level Meeting Pre-defined Criteria | Negative | 1 Participants |
| Crizotinib + Pembrolizumab | Number of Participants With Programmed Death Receptor-1 Ligand-1 (PD-L1) Expression Level Meeting Pre-defined Criteria | Positive | 1 Participants |
| Crizotinib + Pembrolizumab | Number of Participants With Programmed Death Receptor-1 Ligand-1 (PD-L1) Expression Level Meeting Pre-defined Criteria | Strong positive | 0 Participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Number of Participants With Programmed Death Receptor-1 Ligand-1 (PD-L1) Expression Level Meeting Pre-defined Criteria | Negative | 1 Participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Number of Participants With Programmed Death Receptor-1 Ligand-1 (PD-L1) Expression Level Meeting Pre-defined Criteria | Positive | 3 Participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Number of Participants With Programmed Death Receptor-1 Ligand-1 (PD-L1) Expression Level Meeting Pre-defined Criteria | Strong positive | 2 Participants |
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.
Time frame: 2 years
Population: The safety analysis set included all enrolled participants who received at least 1 dose of crizotinib or pembrolizumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | Grade 1 all-causality AE | 0 Participants |
| Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | Grade 2 all-causality AE | 0 Participants |
| Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | Grade 3 all-causality AE | 0 Participants |
| Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | Grade 4 all-causality AE | 1 Participants |
| Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | Grade 5 all-causality AE | 1 Participants |
| Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | All-causality SAE | 2 Participants |
| Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | Crizotinib-related AE | 2 Participants |
| Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | Crizotinib-related SAE | 0 Participants |
| Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | Pembrolizumab-related AE | 2 Participants |
| Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | Pembrolizumab-related SAE | 2 Participants |
| Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | All-causality AE | 2 Participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | Crizotinib-related SAE | 0 Participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | Grade 1 all-causality AE | 1 Participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | All-causality SAE | 1 Participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | Grade 3 all-causality AE | 4 Participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | Grade 2 all-causality AE | 2 Participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | Pembrolizumab-related SAE | 1 Participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | Crizotinib-related AE | 7 Participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | Grade 4 all-causality AE | 0 Participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | Pembrolizumab-related AE | 6 Participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | Grade 5 all-causality AE | 0 Participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Number of Participants With Treatment-Emergent Adverse Events | All-causality AE | 7 Participants |
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Crizotinib + Pembrolizumab | Objective Response Rate (ORR) | 50 percentage of participants |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Objective Response Rate (ORR) | 57.1 percentage of participants |
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Crizotinib + Pembrolizumab | Overall Survival | 452.5 days |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Overall Survival | 428 days |
Secondary
Plasma Concentration Summary of Crizotinib for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of Crizotinib for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | Day 15 of monotherapy: pre-dose | 273 ng/mL |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of Crizotinib for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | Day 15 of monotherapy: 2 hours post-dose | 345 ng/mL |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of Crizotinib for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | Day 15 of monotherapy: 4 hours post-dose | 331 ng/mL |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of Crizotinib for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | Day 1 of Cycle 1: pre-dose | 272.5 ng/mL |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of Crizotinib for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | Day 1 of Cycle 2: pre-dose | 131 ng/mL |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of Crizotinib for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | Day 1 of Cycle 4: pre-dose | 194.5 ng/mL |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of Crizotinib for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | Day 15 of monotherapy: 6 hours post-dose | 278 ng/mL |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of Crizotinib for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | Day 1 of Cycle 6: pre-dose | 249 ng/mL |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of Crizotinib for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | Day 1 of Cycle 8: pre-dose | 244.5 ng/mL |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of Crizotinib for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | End of treatment | 24.65 ng/mL |
Secondary
Plasma Concentration Summary of Crizotinib for Crizotinib + Pembrolizumab Group
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of Crizotinib for Crizotinib + Pembrolizumab Group | Day 1 of Cycle 8: pre-dose | 257 nanograms/milliliter (ng/mL) |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of Crizotinib for Crizotinib + Pembrolizumab Group | End of treatment | 166.04 nanograms/milliliter (ng/mL) |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of Crizotinib for Crizotinib + Pembrolizumab Group | Day 1 of Cycle 1: pre-dose | 0 nanograms/milliliter (ng/mL) |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of Crizotinib for Crizotinib + Pembrolizumab Group | Day 1 of Cycle 2: pre-dose | 379 nanograms/milliliter (ng/mL) |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of Crizotinib for Crizotinib + Pembrolizumab Group | Day 1 of Cycle 4: pre-dose | 147 nanograms/milliliter (ng/mL) |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of Crizotinib for Crizotinib + Pembrolizumab Group | Day 1 of Cycle 6: pre-dose | 235 nanograms/milliliter (ng/mL) |
Secondary
Plasma Concentration Summary of PF-06260182 for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group
PF-06260182 is a metabolite of crizotinib.
Time frame: 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 PF-06260182 concentration measurement.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of PF-06260182 for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | End of treatment | 2.75 ng/mL |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of PF-06260182 for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group | Day 15 of monotherapy: pre-dose | 91.35 ng/mL |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
| Crizotinib + Pembrolizumab | 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 |
Secondary
Plasma Concentration Summary of PF-06260182 for Crizotinib + Pembrolizumab Group
PF-06260182 is a metabolite of crizotinib.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of PF-06260182 for Crizotinib + Pembrolizumab Group | Day 1 of Cycle 1: pre-dose | 0 ng/mL |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of PF-06260182 for Crizotinib + Pembrolizumab Group | Day 1 of Cycle 2: pre-dose | 182 ng/mL |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of PF-06260182 for Crizotinib + Pembrolizumab Group | Day 1 of Cycle 4: pre-dose | 46.4 ng/mL |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of PF-06260182 for Crizotinib + Pembrolizumab Group | Day 1 of Cycle 6: pre-dose | 99.1 ng/mL |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of PF-06260182 for Crizotinib + Pembrolizumab Group | Day 1 of Cycle 8: pre-dose | 67 ng/mL |
| Crizotinib + Pembrolizumab | Plasma Concentration Summary of PF-06260182 for Crizotinib + Pembrolizumab Group | End of treatment | 56.58 ng/mL |
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Crizotinib + Pembrolizumab | Progression Free Survival | 131.5 days |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Progression Free Survival | 211 days |
Secondary
Serum Concentration of Pembrolizumab
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Crizotinib + Pembrolizumab | Serum Concentration of Pembrolizumab | Day 15 of Cycle 1: 336 hours post Day 1 dosing | 19600 ng/mL |
| Crizotinib + Pembrolizumab | Serum Concentration of Pembrolizumab | Day 1 of Cycle 1: pre-dose | 0 ng/mL |
| Crizotinib + Pembrolizumab | Serum Concentration of Pembrolizumab | Day 1 of Cycle 2: pre-dose | 9840 ng/mL |
| Crizotinib + Pembrolizumab | Serum Concentration of Pembrolizumab | Day 8 of Cycle 1: 120 hours post Day 1 dosing | 25550 ng/mL |
| Crizotinib + Pembrolizumab | Serum Concentration of Pembrolizumab | End of treatment | 10800 ng/mL |
| Crizotinib + Pembrolizumab | Serum Concentration of Pembrolizumab | Day 1 of Cycle 1: end of infusion | 63150 ng/mL |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Serum Concentration of Pembrolizumab | Day 1 of Cycle 4: pre-dose | 31600 ng/mL |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Serum Concentration of Pembrolizumab | Day 1 of Cycle 6: pre-dose | 37000 ng/mL |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Serum Concentration of Pembrolizumab | Day 1 of Cycle 8: pre-dose | 38800 ng/mL |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Serum Concentration of Pembrolizumab | Day 1 of Cycle 8: end of infusion | 14300 ng/mL |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Serum Concentration of Pembrolizumab | Day 1 of Cycle 16: pre-dose | 29300 ng/mL |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Serum Concentration of Pembrolizumab | Day 1 of Cycle 12: pre-dose | 99350 ng/mL |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Serum Concentration of Pembrolizumab | End of treatment | 27500 ng/mL |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Serum Concentration of Pembrolizumab | Day 1 of Cycle 1: pre-dose | 0 ng/mL |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Serum Concentration of Pembrolizumab | Day 1 of Cycle 1: end of infusion | 61400 ng/mL |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Serum Concentration of Pembrolizumab | Day 8 of Cycle 1: 120 hours post Day 1 dosing | 26800 ng/mL |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Serum Concentration of Pembrolizumab | Day 15 of Cycle 1: 336 hours post Day 1 dosing | 20100 ng/mL |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Serum Concentration of Pembrolizumab | Day 1 of Cycle 2: pre-dose | 15750 ng/mL |
Secondary
Time to Maximum Plasma Concentration (Tmax) of Crizotinib for Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab Group
Time frame: 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: Data were not collected.
Secondary
Time to Maximum Plasma Concentration (Tmax) of Crizotinib for Crizotinib + Pembrolizumab Group
Time frame: 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.
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.
Time frame: 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: Data were not collected.
Secondary
Time to Maximum Plasma Concentration (Tmax) of PF-06260182 for Crizotinib + Pembrolizumab Group
PF-06260182 is a metabolite of crizotinib.
Time frame: 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.
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Crizotinib + Pembrolizumab | Time to Tumor Response | 57 days |
| Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab | Time to Tumor Response | 83 days |