Trial Outcomes & Findings for A Study Of Combined C- MET Inhibitor And PAN-HER Inhibitor (PF-02341066 And PF-00299804) In Patients With Non- Small Cell Lung Cancer (NCT NCT01121575)

Last Updated: 2015-10-28

Results Overview

AE was any untoward medical occurrence with study drug/ device in a trial participant. Serious adverse event (SAE) was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. AEs were reported from signing of informed consent until 28 days after the last dose of study medication. SAEs were reported after this time frame if considered to be treatment related. The severity of AEs were graded by the investigator using National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) v.4.02 and was assessed as Grade 0: no change from normal or reference range; Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling; Grade 5: death related to AE. However the below table included Grade 3, 4, and 5 AEs.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

70 participants

Primary outcome timeframe

Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)

Results posted on

2015-10-28

Participant Flow

This was a Phase 1, multicenter, open-label, non-randomized study of combined oral crizotinib and oral dacomitinib in participants with advanced non-small cell lung cancer (NSCLC). The study consisted of a dose Escalation Phase and an Expansion Phase. The Expansion Phase consisted of Expansion Cohort 1 and 2 which ran concurrently.

A total of 70 participants were enrolled and received study treatment in the United States (3 centers) and Australia (1 center). 33 participants in Escalation Phase and 37 participants in Expansion Phase (25 participants in Cohort 1 and 12 participants in Cohort 2) received treatment. The last participant completed the study on 11 Feb 2014.

Participant milestones

Participant milestones
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg twice a day (BID) and oral dacomitinib 30 mg once daily (QD). The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Expansion Cohort 1 Participants enrolled in expansion cohort 1 received combined oral crizotinib and oral dacomitinib on a continuous daily schedule of crizotinib 200 mg BID + dacomitinib 30 mg QD. Each cycle was 21 days. If there was unacceptable toxicity or tolerability the dose could be adjusted to a lower combined dose. Expansion Cohort 1 was designed to examine the safety of crizotinib and dacomitinib administered concomitantly in NSCLC participants with acquired resistance to erlotinib or gefitinib.	Expansion Cohort 2 Participants were treated first with single agent dacomitinib at a dose determined by agreement between the investigator and the sponsor, and then, at progression, with combined maximum tolerated dose of crizotinib and dacomitinib (given orally on a continuous schedule in 21-day cycles of crizotinib 200 mg BID + dacomitinib 30 mg QD) as soon as feasible, and no later than 28 days after documentation of progressive disease. Expansion Cohort 2 used the same participant population as Expansion Cohort 1 and was designed to assess the clinical value of adding crizotinib to dacomitinib treatment after disease progression on dacomitinib alone.
Overall Study STARTED	14	6	7	6	25	12
Overall Study Treated	14	6	7	6	25	12
Overall Study COMPLETED	0	0	0	0	0	0
Overall Study NOT COMPLETED	14	6	7	6	25	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg twice a day (BID) and oral dacomitinib 30 mg once daily (QD). The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Expansion Cohort 1 Participants enrolled in expansion cohort 1 received combined oral crizotinib and oral dacomitinib on a continuous daily schedule of crizotinib 200 mg BID + dacomitinib 30 mg QD. Each cycle was 21 days. If there was unacceptable toxicity or tolerability the dose could be adjusted to a lower combined dose. Expansion Cohort 1 was designed to examine the safety of crizotinib and dacomitinib administered concomitantly in NSCLC participants with acquired resistance to erlotinib or gefitinib.	Expansion Cohort 2 Participants were treated first with single agent dacomitinib at a dose determined by agreement between the investigator and the sponsor, and then, at progression, with combined maximum tolerated dose of crizotinib and dacomitinib (given orally on a continuous schedule in 21-day cycles of crizotinib 200 mg BID + dacomitinib 30 mg QD) as soon as feasible, and no later than 28 days after documentation of progressive disease. Expansion Cohort 2 used the same participant population as Expansion Cohort 1 and was designed to assess the clinical value of adding crizotinib to dacomitinib treatment after disease progression on dacomitinib alone.
Overall Study Participant Refused Further Follow-Up	0	0	0	0	5	1
Overall Study Unspecified Reasons	8	6	7	5	13	10
Overall Study Death	6	0	0	1	7	1

Baseline Characteristics

A Study Of Combined C- MET Inhibitor And PAN-HER Inhibitor (PF-02341066 And PF-00299804) In Patients With Non- Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=14 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD n=7 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Expansion Cohort 1 n=25 Participants Participants enrolled in expansion cohort 1 received combined oral crizotinib and oral dacomitinib on a continuous daily schedule of crizotinib 200 mg BID + dacomitinib 30 mg QD. Each cycle was 21 days. If there was unacceptable toxicity or tolerability the dose could be adjusted to a lower combined dose. Expansion Cohort 1 was designed to examine the safety of crizotinib and dacomitinib administered concomitantly in NSCLC participants with acquired resistance to erlotinib or gefitinib.	Expansion Cohort 2 n=12 Participants Participants were treated first with single agent dacomitinib at a dose determined by agreement between the investigator and the sponsor, and then, at progression, with combined maximum tolerated dose of crizotinib and dacomitinib (given orally on a continuous schedule in 21-day cycles of crizotinib 200 mg BID + dacomitinib 30 mg QD) as soon as feasible, and no later than 28 days after documentation of progressive disease. Expansion Cohort 2 used the same participant population as Expansion Cohort 1 and was designed to assess the clinical value of adding crizotinib to dacomitinib treatment after disease progression on dacomitinib alone.	Total n=70 Participants Total of all reporting groups
Age, Continuous	53.6 Years STANDARD_DEVIATION 9.87 • n=5 Participants	61.7 Years STANDARD_DEVIATION 7.53 • n=7 Participants	54.7 Years STANDARD_DEVIATION 11.34 • n=5 Participants	62.2 Years STANDARD_DEVIATION 13.61 • n=4 Participants	61.8 Years STANDARD_DEVIATION 10.83 • n=21 Participants	59.6 Years STANDARD_DEVIATION 11.74 • n=10 Participants	59.1 Years STANDARD_DEVIATION 11.05 • n=115 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	2 Participants n=4 Participants	16 Participants n=21 Participants	9 Participants n=10 Participants	43 Participants n=115 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants	9 Participants n=21 Participants	3 Participants n=10 Participants	27 Participants n=115 Participants

PRIMARY outcome

Timeframe: Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)

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

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=14 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD n=7 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Overview of Treatment-emergent All Causalities Adverse Events (AEs) in Escalation Phase Participants with AEs	14 participants	6 participants	7 participants	6 participants
Overview of Treatment-emergent All Causalities Adverse Events (AEs) in Escalation Phase Participants with Grade 3 or 4 AEs	9 participants	4 participants	5 participants	5 participants
Overview of Treatment-emergent All Causalities Adverse Events (AEs) in Escalation Phase Participants with Grade 5 AEs	3 participants	0 participants	0 participants	1 participants
Overview of Treatment-emergent All Causalities Adverse Events (AEs) in Escalation Phase Participants with SAEs	6 participants	2 participants	1 participants	4 participants

PRIMARY outcome

Timeframe: Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)

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

AE was any untoward medical occurrence with study drug/ device in a trial participant. SAE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. AEs were reported from signing of informed consent until 28 days after the last dose of study medication. SAEs were reported after this time frame if considered to be treatment related. The severity of AEs were graded by the investigator using NCI CTCAE v.4.02 and was assessed as Grade 0: no change from normal or reference range; Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling; Grade 5: death related to AE. However the below table included Grade 3, 4, and 5 AEs.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=25 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=12 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Overview of Treatment-emergent All Causalities AEs in Expansion Phase Participants with AEs	22 Participants	11 Participants	—	—
Overview of Treatment-emergent All Causalities AEs in Expansion Phase Participants with Grade 3 or 4 AEs	12 Participants	8 Participants	—	—
Overview of Treatment-emergent All Causalities AEs in Expansion Phase Participants with Grade 5 AEs	3 Participants	2 Participants	—	—
Overview of Treatment-emergent All Causalities AEs in Expansion Phase Participants with SAEs	8 Participants	8 Participants	—	—

PRIMARY outcome

Timeframe: Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)

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

An AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. SAE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. AEs were reported from signing of informed consent until 28 days after the last dose of study medication. SAEs were reported after this time frame if considered to be treatment related. The severity of AEs were graded by the investigator using NCI CTCAE v.4.02 and was assessed as Grade 0: no change from normal or reference range; Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling; Grade 5: death related to AE. However the below table included Grade 3, 4, and 5 AEs.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=14 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD n=7 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Overview of Treatment-emergent, Treatment-related AEs in Escalation Phase Participants with treatment-related AEs	14 participants	6 participants	7 participants	6 participants
Overview of Treatment-emergent, Treatment-related AEs in Escalation Phase Participants with treatment-related Grade 3/ 4 AEs	8 participants	3 participants	3 participants	3 participants
Overview of Treatment-emergent, Treatment-related AEs in Escalation Phase Participants with treatment-related Grade 5 AEs	0 participants	0 participants	0 participants	0 participants
Overview of Treatment-emergent, Treatment-related AEs in Escalation Phase Participants with treatment-related SAEs	1 participants	2 participants	0 participants	1 participants

PRIMARY outcome

Timeframe: Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)

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

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=25 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=12 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Overview of Treatment-emergent, Treatment-related AEs in Expansion Phase Participants with treatment-related AEs	22 Participants	11 Participants	—	—
Overview of Treatment-emergent, Treatment-related AEs in Expansion Phase Participants with treatment-related Grade 3/ 4 AEs	7 Participants	6 Participants	—	—
Overview of Treatment-emergent, Treatment-related AEs in Expansion Phase Participants with treatment-related Grade 5 AEs	0 Participants	0 Participants	—	—
Overview of Treatment-emergent, Treatment-related AEs in Expansion Phase Participants with treatment-related SAEs	3 Participants	3 Participants	—	—

PRIMARY outcome

Timeframe: Cycle 1 (4 weeks)

Population: The DLT evaluable population was defined as safety analysis (SA) participants in the Dose Escalation phase who did not have a major treatment deviation during the first cycle.

DLTs were those AEs which occurred in Cycle 1 of treatment in Dose Escalation Phase which may be attributed to study drug \[combined Crizotinib (PF-02341066) plus Dacomitinib (PF-00299804)\] without a clear alternative explanation and despite the use of adequate/maximal medical intervention as dictated by local institutional clinical practices or the judgment of the investigator. The following events were considered DLTs (using CTCAE version 4.02);1. Grade ≥4 hematologic events. 2. Grade ≥3 non-hematological events (except Grade 3/4 asymptomatic hypophosphatemia and Grade 3/4 hyperuricemia without signs and symptoms of gout). Nausea, vomiting or diarrhea had to have persisted at Grade 3 or 4 despite maximal medical therapy. Grade 3 hypertension will be considered a DLT only if the event is unmanageable by standard approved pharmacologic agents or if the symptomatic sequelae are identified despite appropriate medical intervention.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=14 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD n=7 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Number of Participants With Dose Limiting Toxicities (DLTs) in Escalation Phase Grade 3 Alanine aminotransferase increased	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Dose Limiting Toxicities (DLTs) in Escalation Phase Grade 3 Diarrhoea	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Dose Limiting Toxicities (DLTs) in Escalation Phase Grade 3 Mucosal inflammation	0 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)

Population: The response evaluable population included participants in safety analysis population who had an adequate Baseline tumor assessment.

If a participant had not achieved an objective response with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) - 1.1 as determined by the investigators, relative to the response evaluable population, but remained stable for at least 6 weeks after first dose, then the best overall response for such a participant was considered as stable disease.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=14 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD n=7 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Number of Participants With Stable Disease and Stable Disease Duration in Escalation Phase Stable Disease	10 Participants	3 Participants	2 Participants	5 Participants
Number of Participants With Stable Disease and Stable Disease Duration in Escalation Phase 0- < 3 months	3 Participants	2 Participants	1 Participants	0 Participants
Number of Participants With Stable Disease and Stable Disease Duration in Escalation Phase 3- < 6 months	6 Participants	1 Participants	1 Participants	3 Participants
Number of Participants With Stable Disease and Stable Disease Duration in Escalation Phase 6- < 9 months	1 Participants	0 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)

Population: The response evaluable population included participants in safety analysis population who had an adequate Baseline tumor assessment.

If a participant had not achieved an objective response with confirmed complete response (CR) or partial response (PR) according to RECIST (1.1) as determined by the investigators, relative to the response evaluable population, but remained stable for at least 6 weeks after first dose, then the best overall response for such a participant was considered as stable disease.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=22 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=12 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Number of Participants With Stable Disease and Stable Disease Duration in Expansion Phase Stable Disease	6 Participants	5 Participants	—	—
Number of Participants With Stable Disease and Stable Disease Duration in Expansion Phase 0- < 3 months	1 Participants	0 Participants	—	—
Number of Participants With Stable Disease and Stable Disease Duration in Expansion Phase 3- < 6 months	4 Participants	4 Participants	—	—
Number of Participants With Stable Disease and Stable Disease Duration in Expansion Phase 6- < 9 months	1 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)

Population: The response evaluable population included participants in safety analysis population who had an adequate Baseline tumor assessment.

ORR was defined as the percent of participants with CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) determined by study physicians, relative to the response evaluable population. Participants were considered non-responders until proven otherwise. Thus, participants who: 1) Did not have CR or PR while on study, or 2) Did not have a post-baseline tumor evaluation, or 3) Received anti-tumor treatment other than the study medication prior to reaching a CR or PR, or 4) Died, in progress, or drop out for any reason prior to reaching a CR or PR, were counted as non-responders in the assessment of ORR. To be assigned a status of PR or CR, changes in tumor measurements in participants with responding tumors were confirmed by repeated tumor assessment that were performed 4 weeks after the criteria for response were first met.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=14 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD n=7 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Number of Participants With Objective Response Rate (ORR) in Escalation Phase	0 Participants Interval 0.0 to 23.2	0 Participants Interval 0.0 to 45.9	0 Participants Interval 0.0 to 41.0	0 Participants Interval 0.0 to 45.9

SECONDARY outcome

Timeframe: From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)

Population: The response evaluable population included participants in safety analysis population who had an adequate Baseline tumor assessment.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=22 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=12 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Number of Participants With ORR in Expansion Phase	1 Participants Interval 0.1 to 22.8	0 Participants Interval 0.0 to 26.5	—	—

SECONDARY outcome

Timeframe: From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)

Population: This Outcome Measure was only assessed for participants with response.

This outcome measure presented the duration of response for one participant in expansion cohort 1 who showed partial response.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=1 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Duration of Response for the Only Participant Shown Partial Response in Expansion Phase	6.29 Weeks	—	—	—

SECONDARY outcome

Timeframe: From randomization to objective tumor progression or death (up to post treatment follow-up as 28-35 days after last dose of study treatment)

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

PFS was defined as the time from the date of the first dose to the date of the first documentation of objective tumor progression according to RECIST 1.1 or death on study due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=14 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD n=7 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Progression Free Survival (PFS) in Escalation Phase	3.1 Months Interval 1.6 to 5.5	3.0 Months Interval 1.5 to 4.4	1.7 Months Interval 1.6 to 4.6	4.4 Months Interval 1.6 to 7.2

SECONDARY outcome

Timeframe: From randomization to objective tumor progression or death (up to post treatment follow-up as 28-35 days after last dose of study treatment)

Population: The safety analysis population included all enrolled participants who had received at least 1 dose of study medication. In Expansion Cohort 1, two participants had censored reasons of "no adequate baseline", of which one participant had a censored reason "no tumor assessment data available.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=23 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=12 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Progression Free Survival (PFS) in Expansion Phase	2.1 Months Interval 1.4 to 4.4	2.1 Months Interval 1.4 to 5.3	—	—

SECONDARY outcome

Timeframe: Baseline

Population: The tumor analysis population included participants in safety analysis population who had a screening and on-treatment tumor biopsy for assessment of tumor biomarkers.

Tumor biomarkers such as HGF, EGFR, and c-Met were analyzed in tumor cells (neoplastic compartment) of tumor specimens from both expansion cohorts 1 and 2 by IHC. The H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+, where 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum calculated score of 0 to maximum calculated score of 300, where 0 correspond to no expression and maximum score of 300 indicates the strongest expression. However, the biomarker expression level (higher or lower) was not a predictor of outcome.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=23 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=12 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Expression Analysis of Tumor Biomarkers (HGF, EGFR, and c-Met ) at Baseline Using Immunohistochemistry (IHC) Method HGF (N= 19, 11)	40.0 H-Score Interval 0.0 to 280.0	67.0 H-Score Interval 0.0 to 104.0	—	—
Expression Analysis of Tumor Biomarkers (HGF, EGFR, and c-Met ) at Baseline Using Immunohistochemistry (IHC) Method EGFR (N= 14, 8)	193.2 H-Score Interval 2.0 to 300.0	170.0 H-Score Interval 7.0 to 300.0	—	—
Expression Analysis of Tumor Biomarkers (HGF, EGFR, and c-Met ) at Baseline Using Immunohistochemistry (IHC) Method cMet (N= 19, 11)	125.0 H-Score Interval 0.0 to 300.0	165.0 H-Score Interval 20.0 to 299.0	—	—

SECONDARY outcome

Timeframe: Baseline

Population: The tumor analysis population included participants in safety analysis population who had a screening and on-treatment tumor biopsy for assessment of tumor biomarkers.

Expression of tumor biomarkers EGFR and cMet at Baseline (using FISH method) are presented in this outcome measure.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=23 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=12 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Expression Analysis of Tumor Biomarkers (EGFR, and c-Met) at Baseline Using Fluorescent in Situ Hybridization (FISH) Method Ratio of Red to Green of EGFR (N= 11, 11)	1.580 Ratio Interval 0.98 to 3.59	1.180 Ratio Interval 0.94 to 4.63	—	—
Expression Analysis of Tumor Biomarkers (EGFR, and c-Met) at Baseline Using Fluorescent in Situ Hybridization (FISH) Method Ratio of Green to Orange for cMET (N = 19, 11)	1.040 Ratio Interval 0.43 to 2.12	1.000 Ratio Interval 0.88 to 1.1	—	—

SECONDARY outcome

Timeframe: Baseline

Population: The tumor analysis population included participants in safety analysis population who had a screening and on-treatment tumor biopsy for assessment of tumor biomarkers.

Participants showed amplification of c-Met, HER2, and EGFR in the tumor cells and gene rearrangement of ALK are presented in this outcome measure.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=23 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=12 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Number of Participants With c-Met, HER2, EGFR Amplification and ALK Rearrangement at Baseline Using FISH Method c-Met amplification (N= 19, 11)	1 Participants Interval 0.98 to 3.59	0 Participants Interval 0.94 to 4.63	—	—
Number of Participants With c-Met, HER2, EGFR Amplification and ALK Rearrangement at Baseline Using FISH Method HER2 amplification (N= 19, 7)	0 Participants	0 Participants	—	—
Number of Participants With c-Met, HER2, EGFR Amplification and ALK Rearrangement at Baseline Using FISH Method EGFR amplification (N= 11,11)	2 Participants	3 Participants	—	—
Number of Participants With c-Met, HER2, EGFR Amplification and ALK Rearrangement at Baseline Using FISH Method ALK rearrangement (N= 19, 11)	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: At screening and Cycle 1 Day 1 (C1D1) (6 hours post dose), and C1D15, C2D1, C2D15 (all predose).

Population: The soluble protein analysis population included participants in safety analysis who had a screening or C1D1 soluble protein assessment, and at least one on-treatment soluble protein assessment (C1D14 C2D1 or C2D14).

This outcome measure presented the plasma concentration of sMet at different study visits. s-Met was analyzed using an enzyme-linked immunosorbent assay (ELISA).

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=21 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=7 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Plasma Concentration of sMet by Study Visits Baseline at Screening	1353411.8 pg/mL Standard Deviation 349746.88 • Interval 2.67 to 10.4	1557000.0 pg/mL Standard Deviation 514352.02 • Interval 2.05 to 25.2	—	—
Plasma Concentration of sMet by Study Visits C1D1	1519047.6 pg/mL Standard Deviation 230995.77	1450500.0 pg/mL Standard Deviation 553557.13	—	—
Plasma Concentration of sMet by Study Visits C1D15	1483157.9 pg/mL Standard Deviation 243904.64	1676666.7 pg/mL Standard Deviation 540246.86	—	—
Plasma Concentration of sMet by Study Visits C2D1	1525666.7 pg/mL Standard Deviation 394836.61	1540000.0 pg/mL Standard Deviation 315515.45	—	—
Plasma Concentration of sMet by Study Visits C2D15	1564666.7 pg/mL Standard Deviation 224367.90	1602500.0 pg/mL Standard Deviation 126589.89	—	—

SECONDARY outcome

Timeframe: Baseline

Population: The tumor analysis population included participants in safety analysis population who had a screening and on-treatment tumor biopsy for assessment of tumor biomarkers.

Sample analyses were performed in accordance to Good Laboratory Practice (GLP) guidance and included mutation detection for EGFR gene.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=23 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=12 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Number of Participants With EGFR Mutation at Baseline Exon 18 (G719X)	1 Participants	1 Participants	—	—
Number of Participants With EGFR Mutation at Baseline Exon 19 (Deletion)	6 Participants	3 Participants	—	—
Number of Participants With EGFR Mutation at Baseline Exon 20 (T790M)	6 Participants	3 Participants	—	—
Number of Participants With EGFR Mutation at Baseline Exon 20 (T790M/S768I)	1 Participants	0 Participants	—	—
Number of Participants With EGFR Mutation at Baseline Exon 20 (S768I)	0 Participants	1 Participants	—	—
Number of Participants With EGFR Mutation at Baseline Exon 21 (L858R)	6 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: Baseline

Population: The tumor analysis population included participants in safety analysis population who had a screening and on-treatment tumor biopsy for assessment of tumor biomarkers.

Sample analyses were performed in accordance to GLP guidance and included mutation detection for KRAS gene.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=23 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=12 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Number of Participants With KRAS Mutation (GLY12CYS) at Baseline	1 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Baseline

Population: The tumor analysis population included participants in safety analysis population who had a screening and on-treatment tumor biopsy for assessment of tumor biomarkers.

Sample analyses were performed in accordance to GLP guidance and included mutation detection for PIK3CA gene.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=23 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=12 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Number of Participants With PIK3CA Mutation at Baseline Exon 20 (M1004I) (N= 14, 6)	1 Participants	0 Participants	—	—
Number of Participants With PIK3CA Mutation at Baseline Exon 20 (Q1061K) (N= 14, 6)	1 Participants	0 Participants	—	—
Number of Participants With PIK3CA Mutation at Baseline Exon 20 (H1047R) (N= 14, 6)	2 Participants	0 Participants	—	—
Number of Participants With PIK3CA Mutation at Baseline Exon 9 (E545K) (N= 14, 6)	1 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Baseline

Population: The tumor analysis population included participants in safety analysis population who had a screening and on-treatment tumor biopsy for assessment of tumor biomarkers. However, number of participants analyzed in the below table included the participants evaluated for ROS1 gene translocation.

Sample analyses were performed in accordance to GLP guidance and included translocation detection (RNA based) for ROS1 gene.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=6 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=3 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Number of Participants With ROS1 Gene Translocation at Baseline	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Cycle 1 (C1)/Day 1 (D1), C1D15

Population: The PK parameter analysis population was defined as all participants in the safety analysis population who had at least 1 of the PK parameters of interest. N= Number of participants in the treatment group in the indicated population. n= Number of participants contributing to the summary statistics.

At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included AUClast for crizotinib and PF-06260182. AUClast was calculated using Linear/Log trapezoidal method.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=11 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD n=7 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Area Under the Plasma Concentration-time Profile From Time Zero to the Last Quantifiable Concentration (AUClast) Crizotinib C1D1 - single dose (n= 11, 6, 7, 6)	509.7 ng•hr/mL Geometric Coefficient of Variation 62	420.8 ng•hr/mL Geometric Coefficient of Variation 53	506.6 ng•hr/mL Geometric Coefficient of Variation 29	656.6 ng•hr/mL Geometric Coefficient of Variation 65
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Area Under the Plasma Concentration-time Profile From Time Zero to the Last Quantifiable Concentration (AUClast) PF-06260182 C1D15 - multiple dose (n=8, 3, 6, 5)	382.3 ng•hr/mL Geometric Coefficient of Variation 52	593.5 ng•hr/mL Geometric Coefficient of Variation 53	440.5 ng•hr/mL Geometric Coefficient of Variation 37	532.0 ng•hr/mL Geometric Coefficient of Variation 68
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Area Under the Plasma Concentration-time Profile From Time Zero to the Last Quantifiable Concentration (AUClast) Crizotinib C1D15 multiple dose (n=8, 3, 6, 5)	1759 ng•hr/mL Geometric Coefficient of Variation 39	2464 ng•hr/mL Geometric Coefficient of Variation 14	1732 ng•hr/mL Geometric Coefficient of Variation 35	1672 ng•hr/mL Geometric Coefficient of Variation 44
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Area Under the Plasma Concentration-time Profile From Time Zero to the Last Quantifiable Concentration (AUClast) PF-06260182 C1D1 - single dose (n= 11, 6, 7, 6)	121.3 ng•hr/mL Geometric Coefficient of Variation 76	103.2 ng•hr/mL Geometric Coefficient of Variation 74	121.6 ng•hr/mL Geometric Coefficient of Variation 29	220.7 ng•hr/mL Geometric Coefficient of Variation 55

SECONDARY outcome

Timeframe: C1D1, C1D15

At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). AUC10 was calculated using Linear/Log trapezoidal method. The below analysis table included geometric Mean and Geometric Coefficient of Variation of AUC10 for crizotinib and PF-06260182. Arithmetic mean was presented if the n=2.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=11 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD n=7 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Area Under the Plasma Concentration-time Curve 10 (AUC10) Crizotinib C1D1 - single dose (n= 8, 3, 4, 6)	624.9 ng•hr/mL Geometric Coefficient of Variation 57	500.8 ng•hr/mL Geometric Coefficient of Variation 9	559.6 ng•hr/mL Geometric Coefficient of Variation 26	655.8 ng•hr/mL Geometric Coefficient of Variation 65
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Area Under the Plasma Concentration-time Curve 10 (AUC10) Crizotinib C1D15 multiple dose (n= 5, 2, 6, 5)	2000 ng•hr/mL Geometric Coefficient of Variation 43	2620 ng•hr/mL Geometric Coefficient of Variation NA Not applicable as arithmetic mean is presented for n = 2.	1732 ng•hr/mL Geometric Coefficient of Variation 35	1644 ng•hr/mL Geometric Coefficient of Variation 44
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Area Under the Plasma Concentration-time Curve 10 (AUC10) PF-06260182 C1D1 - single dose (n= 8, 3, 4, 6)	162.1 ng•hr/mL Geometric Coefficient of Variation 57	127.6 ng•hr/mL Geometric Coefficient of Variation 32	141.5 ng•hr/mL Geometric Coefficient of Variation 25	228.0 ng•hr/mL Geometric Coefficient of Variation 57
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Area Under the Plasma Concentration-time Curve 10 (AUC10) PF-06260182 C1D15 - multiple dose (n= 5, 2, 6, 5)	452.5 ng•hr/mL Geometric Coefficient of Variation 48	798.0 ng•hr/mL Geometric Coefficient of Variation NA Not applicable as arithmetic mean is presented for n = 2.	473.3 ng•hr/mL Geometric Coefficient of Variation 39	525.5 ng•hr/mL Geometric Coefficient of Variation 68

SECONDARY outcome

Timeframe: C1D1, C1D15

At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Cmax for crizotinib and PF-06260182. Cmax was observed directly from data.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=11 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD n=7 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Maximum Plasma Concentration (Cmax) Crizotinib C1D1 - single dose (n= 11, 6, 7, 6)	84.24 ng/mL Geometric Coefficient of Variation 58	94.13 ng/mL Geometric Coefficient of Variation 22	90.86 ng/mL Geometric Coefficient of Variation 29	114.0 ng/mL Geometric Coefficient of Variation 61
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Maximum Plasma Concentration (Cmax) Crizotinib C1D15 multiple dose (n=8, 3, 6, 5)	231.5 ng/mL Geometric Coefficient of Variation 41	329.7 ng/mL Geometric Coefficient of Variation 12	218.1 ng/mL Geometric Coefficient of Variation 33	268.9 ng/mL Geometric Coefficient of Variation 77
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Maximum Plasma Concentration (Cmax) PF-06260182 C1D1 - single dose (n= 11, 6, 7, 6)	18.50 ng/mL Geometric Coefficient of Variation 72	22.37 ng/mL Geometric Coefficient of Variation 26	20.97 ng/mL Geometric Coefficient of Variation 29	34.33 ng/mL Geometric Coefficient of Variation 61
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Maximum Plasma Concentration (Cmax) PF-06260182 C1D15 - multiple dose (n=8, 3, 6, 5)	49.73 ng/mL Geometric Coefficient of Variation 50	78.45 ng/mL Geometric Coefficient of Variation 44	57.56 ng/mL Geometric Coefficient of Variation 34	83.23 ng/mL Geometric Coefficient of Variation 91

SECONDARY outcome

Timeframe: C1D1, C1D15

At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Tlast for crizotinib and PF-06260182. Tlast was observed directly from data.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=11 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD n=7 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Time of Last Quantifiable Concentration (Tlast) Crizotinib C1D1 - single dose (n= 11, 6, 7, 6)	9.92 Hour Full Range 58 • Interval 7.83 to 10.1	9.33 Hour Full Range 22 • Interval 4.08 to 10.0	9.05 Hour Full Range 29 • Interval 7.55 to 9.95	9.75 Hour Full Range 61 • Interval 9.0 to 10.2
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Time of Last Quantifiable Concentration (Tlast) Crizotinib C1D15 multiple dose (n=8, 3, 6, 5)	9.29 Hour Full Range 41 • Interval 7.62 to 9.98	9.42 Hour Full Range 25 • Interval 8.0 to 9.92	9.05 Hour Full Range 47 • Interval 9.0 to 9.57	10.2 Hour Full Range 35 • Interval 10.0 to 10.5
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Time of Last Quantifiable Concentration (Tlast) PF-06260182 C1D1 - single dose (n= 11, 6, 7, 6)	9.92 Hour Full Range 72 • Interval 7.83 to 10.1	9.33 Hour Full Range 26 • Interval 4.08 to 10.0	9.05 Hour Full Range 29 • Interval 7.55 to 9.95	9.75 Hour Full Range 61 • Interval 9.0 to 10.2
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Time of Last Quantifiable Concentration (Tlast) PF-06260182 C1D15 - multiple dose (n=8, 3, 6, 5)	9.29 Hour Full Range 50 • Interval 7.62 to 9.98	9.42 Hour Full Range 44 • Interval 8.0 to 9.92	9.05 Hour Full Range 34 • Interval 9.0 to 9.57	10.2 Hour Full Range 91 • Interval 10.0 to 10.5

SECONDARY outcome

Timeframe: C1D1, C1D15

At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Tmax for crizotinib and PF-06260182. Tmax was observed directly from data as time of first occurrence.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=11 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD n=7 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase -Time to Maximum Plasma Concentration (Tmax) Crizotinib C1D1 - single dose (n= 11, 6, 7, 6)	3.00 Hour Full Range 58 • Interval 1.0 to 6.0	3.53 Hour Full Range 22 • Interval 2.0 to 4.0	3.92 Hour Full Range 29 • Interval 2.0 to 6.07	3.06 Hour Full Range 61 • Interval 3.0 to 4.0
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase -Time to Maximum Plasma Concentration (Tmax) Crizotinib C1D15 multiple dose (n=8, 3, 6, 5)	1.68 Hour Full Range 41 • Interval 0.0 to 7.97	6.17 Hour Full Range 25 • Interval 3.97 to 8.0	2.00 Hour Full Range 47 • Interval 0.0 to 6.0	6.00 Hour Full Range 35 • Interval 1.98 to 8.0
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase -Time to Maximum Plasma Concentration (Tmax) PF-06260182 C1D1 - single dose (n= 11, 6, 7, 6)	4.07 Hour Full Range 72 • Interval 3.0 to 8.0	4.00 Hour Full Range 26 • Interval 3.02 to 6.05	3.98 Hour Full Range 29 • Interval 3.0 to 6.07	4.99 Hour Full Range 61 • Interval 3.03 to 6.1
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase -Time to Maximum Plasma Concentration (Tmax) PF-06260182 C1D15 - multiple dose (n=8, 3, 6, 5)	4.03 Hour Full Range 50 • Interval 0.0 to 7.97	6.17 Hour Full Range 44 • Interval 3.97 to 8.0	4.09 Hour Full Range 34 • Interval 3.0 to 6.02	6.00 Hour Full Range 91 • Interval 4.02 to 6.05

SECONDARY outcome

Timeframe: C1D1, C1D15

At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included AUClast for dacomitinib and PF-05199265. AUClast was calculated using Linear/Log trapezoidal method.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=11 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD n=7 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUClast Dacomitinib C1D1 - single dose (n= 10, 6, 7, 5)	208.3 ng•hr/mL Geometric Coefficient of Variation 72 • Interval 1.0 to 6.0	132.3 ng•hr/mL Geometric Coefficient of Variation 153 • Interval 2.0 to 4.0	146.3 ng•hr/mL Geometric Coefficient of Variation 86 • Interval 2.0 to 6.07	307.7 ng•hr/mL Geometric Coefficient of Variation 56 • Interval 3.0 to 4.0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUClast Dacomitinib C1D15 multiple dose (n= 8, 4, 6, 4)	1339 ng•hr/mL Geometric Coefficient of Variation 47 • Interval 0.0 to 7.97	2343 ng•hr/mL Geometric Coefficient of Variation 70 • Interval 3.97 to 8.0	1212 ng•hr/mL Geometric Coefficient of Variation 15 • Interval 0.0 to 6.0	1775 ng•hr/mL Geometric Coefficient of Variation 31 • Interval 1.98 to 8.0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUClast PF-5199265 C1D1 - single dose (n= 8, 6, 6, 6)	27.68 ng•hr/mL Geometric Coefficient of Variation 80 • Interval 3.0 to 8.0	7.438 ng•hr/mL Geometric Coefficient of Variation 115 • Interval 3.02 to 6.05	10.19 ng•hr/mL Geometric Coefficient of Variation 190 • Interval 3.0 to 6.07	55.00 ng•hr/mL Geometric Coefficient of Variation 75 • Interval 3.03 to 6.1
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUClast PF-06260182 C1D15 - multiple dose (n= 8, 4, 6, 4)	51.48 ng•hr/mL Geometric Coefficient of Variation 108 • Interval 0.0 to 7.97	52.24 ng•hr/mL Geometric Coefficient of Variation 78 • Interval 3.97 to 8.0	44.97 ng•hr/mL Geometric Coefficient of Variation 90 • Interval 3.0 to 6.02	161.0 ng•hr/mL Geometric Coefficient of Variation 33 • Interval 4.02 to 6.05

SECONDARY outcome

Timeframe: C1D1, C1D15

At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included AUC24 for dacomitinib and PF-05199265. AUC24 was calculated using Linear/Log trapezoidal method.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=11 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD n=7 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUC24 Dacomitinib C1D1 - single dose (n= 8, 3, 5, 5)	252.7 ng•hr/mL Geometric Coefficient of Variation 61 • Interval 1.0 to 6.0	347.9 ng•hr/mL Geometric Coefficient of Variation 26 • Interval 2.0 to 4.0	223.4 ng•hr/mL Geometric Coefficient of Variation 23 • Interval 2.0 to 6.07	306.6 ng•hr/mL Geometric Coefficient of Variation 57 • Interval 3.0 to 4.0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUC24 Dacomitinib C1D15 multiple dose (n= 8, 4, 6, 4)	1336 ng•hr/mL Geometric Coefficient of Variation 48 • Interval 0.0 to 7.97	2334 ng•hr/mL Geometric Coefficient of Variation 69 • Interval 3.97 to 8.0	1203 ng•hr/mL Geometric Coefficient of Variation 15 • Interval 0.0 to 6.0	1745 ng•hr/mL Geometric Coefficient of Variation 30 • Interval 1.98 to 8.0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUC24 PF-5199265 C1D1 - single dose (n= 9, 3, 5, 6)	28.57 ng•hr/mL Geometric Coefficient of Variation 87 • Interval 3.0 to 8.0	14.80 ng•hr/mL Geometric Coefficient of Variation 51 • Interval 3.02 to 6.05	16.08 ng•hr/mL Geometric Coefficient of Variation 169 • Interval 3.0 to 6.07	54.72 ng•hr/mL Geometric Coefficient of Variation 76 • Interval 3.03 to 6.1
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUC24 PF-06260182 C1D15 - multiple dose (n= 8, 4, 6, 4)	51.37 ng•hr/mL Geometric Coefficient of Variation 108 • Interval 0.0 to 7.97	51.97 ng•hr/mL Geometric Coefficient of Variation 78 • Interval 3.97 to 8.0	44.72 ng•hr/mL Geometric Coefficient of Variation 90 • Interval 3.0 to 6.02	158.1 ng•hr/mL Geometric Coefficient of Variation 31 • Interval 4.02 to 6.05

SECONDARY outcome

Timeframe: C1D1, C1D15

At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Cmax for dacomitinib and PF-05199265. Cmax was observed directly from data.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=11 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD n=7 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Cmax Dacomitinib C1D1 - single dose (n= 10, 6, 7, 5)	15.56 ng/mL Geometric Coefficient of Variation 58 • Interval 1.0 to 6.0	17.49 ng/mL Geometric Coefficient of Variation 23 • Interval 2.0 to 4.0	12.40 ng/mL Geometric Coefficient of Variation 21 • Interval 2.0 to 6.07	18.22 ng/mL Geometric Coefficient of Variation 64 • Interval 3.0 to 4.0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Cmax Dacomitinib C1D15 multiple dose (n= 8, 4, 6, 4)	65.00 ng/mL Geometric Coefficient of Variation 52 • Interval 0.0 to 7.97	122.4 ng/mL Geometric Coefficient of Variation 75 • Interval 3.97 to 8.0	57.04 ng/mL Geometric Coefficient of Variation 13 • Interval 0.0 to 6.0	86.81 ng/mL Geometric Coefficient of Variation 38 • Interval 1.98 to 8.0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Cmax PF-5199265 C1D1 - single dose (n= 10, 6, 6, 7)	1.894 ng/mL Geometric Coefficient of Variation 89 • Interval 3.0 to 8.0	0.9888 ng/mL Geometric Coefficient of Variation 79 • Interval 3.02 to 6.05	0.8833 ng/mL Geometric Coefficient of Variation 130 • Interval 3.0 to 6.07	3.193 ng/mL Geometric Coefficient of Variation 74 • Interval 3.03 to 6.1
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Cmax PF-06260182 C1D15 - multiple dose (n= 8, 4, 6, 4)	2.367 ng/mL Geometric Coefficient of Variation 115 • Interval 0.0 to 7.97	2.649 ng/mL Geometric Coefficient of Variation 75 • Interval 3.97 to 8.0	2.073 ng/mL Geometric Coefficient of Variation 95 • Interval 3.0 to 6.02	7.560 ng/mL Geometric Coefficient of Variation 34 • Interval 4.02 to 6.05

SECONDARY outcome

Timeframe: C1D1, C1D15

At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Tlast for dacomitinib and PF-05199265. Tlast was observed directly from data.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=11 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD n=7 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tlast Dacomitinib C1D1 - single dose (n= 11, 6, 7, 5)	24.0 Hour Full Range 8.00 • Interval 8.0 to 24.6	15.9 Hour Full Range 15.9 • Interval 4.08 to 24.0	23.6 Hour Full Range 24.0 • Interval 7.55 to 24.1	24.0 Hour Interval 23.0 to 24.3
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tlast Dacomitinib C1D15 multiple dose (n= 8, 4, 6, 4)	24.00 Hour Interval 23.0 to 24.3	23.9 Hour Interval 23.5 to 24.5	23.9 Hour Interval 22.9 to 24.8	24.4 Hour Interval 24.0 to 25.6
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tlast PF-5199265 C1D1 - single dose (n= 8, 6, 6, 6)	24.0 Hour Interval 8.0 to 24.6	15.9 Hour Interval 4.08 to 24.0	23.5 Hour Interval 7.55 to 24.1	24.1 Hour Interval 23.0 to 24.5
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tlast PF-06260182 C1D15 - multiple dose (n= 8, 4, 6, 4)	24.0 Hour Interval 23.0 to 24.3	23.9 Hour Interval 23.5 to 24.5	23.9 Hour Interval 22.9 to 24.8	24.4 Hour Interval 24.0 to 25.6

SECONDARY outcome

Timeframe: C1D1, C1D15

At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Tmax for dacomitinib and PF-05199265. Tmax was observed directly from data as time of first occurrence.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=11 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD n=7 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD n=6 Participants Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tmax Dacomitinib C1D1 - single dose (n= 11, 6, 7, 5)	5.99 Hour Full Range 8.00 • Interval 3.93 to 24.1	8.03 Hour Full Range 15.9 • Interval 4.08 to 24.0	6.00 Hour Full Range 24.0 • Interval 5.92 to 8.05	6.17 Hour Interval 5.92 to 8.0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tmax Dacomitinib C1D15 multiple dose (n= 8, 4, 6, 4)	6.00 Hour Interval 0.0 to 23.1	5.09 Hour Interval 3.97 to 23.5	6.09 Hour Interval 4.15 to 8.13	5.00 Hour Interval 4.0 to 6.0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tmax PF-5199265 C1D1 - single dose (n= 8, 6, 6, 6)	6.95 Hour Interval 3.93 to 24.1	4.04 Hour Interval 3.97 to 8.0	6.78 Hour Interval 3.98 to 8.05	6.08 Hour Interval 3.98 to 24.3
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tmax PF-06260182 C1D15 - multiple dose (n= 8, 4, 6, 4)	6.98 Hour Interval 0.0 to 23.1	3.95 Hour Interval 2.0 to 6.17	5.92 Hour Interval 0.0 to 23.9	2.00 Hour Interval 0.0 to 5.98

SECONDARY outcome

Timeframe: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)

Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for AUClast. AUClast was calculated using Linear/Log trapezoidal method.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=19 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=19 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - AUClast Crizotinib (n = 16, 13)	2223 ng•hr/mL Geometric Coefficient of Variation 53 • Interval 3.93 to 24.6	1365 ng•hr/mL Geometric Coefficient of Variation 47 • Interval 4.08 to 24.0	—	—
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - AUClast PF-06260182 (n = 16, 13)	616.3 ng•hr/mL Geometric Coefficient of Variation 77	356.6 ng•hr/mL Geometric Coefficient of Variation 61	—	—

SECONDARY outcome

Timeframe: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)

Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for AUC10. AUC10 was calculated using Linear/Log trapezoidal method.

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=19 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=19 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - AUC10 Crizotinib (n = 11, 9)	2167 ng•hr/mL Geometric Coefficient of Variation 56 • Interval 3.93 to 24.6	1489 ng•hr/mL Geometric Coefficient of Variation 44 • Interval 4.08 to 24.0	—	—
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - AUC10 PF-06260182 (n = 11, 9)	634.3 ng•hr/mL Geometric Coefficient of Variation 82	422.3 ng•hr/mL Geometric Coefficient of Variation 55	—	—

SECONDARY outcome

Timeframe: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=19 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=19 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Cmin Crizotinib (n = 16, 13)	181.8 ng/mL Geometric Coefficient of Variation 64 • Interval 3.93 to 24.6	102.8 ng/mL Geometric Coefficient of Variation 51 • Interval 4.08 to 24.0	—	—
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Cmin PF-06260182 (n = 16, 13)	47.22 ng/mL Geometric Coefficient of Variation 99	25.53 ng/mL Geometric Coefficient of Variation 60	—	—

SECONDARY outcome

Timeframe: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=19 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=19 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Cmax Crizotinib (n = 16, 13)	306.0 ng/mL Geometric Coefficient of Variation 57 • Interval 3.93 to 24.6	191.5 ng/mL Geometric Coefficient of Variation 43 • Interval 4.08 to 24.0	—	—
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Cmax PF-06260182 (n = 16, 13)	82.92 ng/mL Geometric Coefficient of Variation 79	51.15 ng/mL Geometric Coefficient of Variation 56	—	—

SECONDARY outcome

Timeframe: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)

Outcome measures

Outcome measures
Measure	Crizotinib 200 mg BID/ Dacomitinib 30 mg QD n=19 Participants Participants enrolled in dose escalation phase received combined oral crizotinib 200 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 200 mg BID/ Dacomitinib 45 mg QD n=19 Participants Participants received combined oral crizotinib 200 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg BID/ Dacomitinib 30 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 30 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.	Crizotinib 250 mg QD/ Dacomitinib 45 mg QD Participants received combined oral crizotinib 250 mg BID and oral dacomitinib 45 mg QD. The first cycle was for 28 days thereafter, each cycle was 21 days.
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Tlast Crizotinib (n = 16, 13)	9.650 Hour Full Range 57 • Interval 7.63 to 10.1	9.000 Hour Full Range 43 • Interval 7.67 to 10.0	—	—
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Tlast PF-06260182 (n = 16, 13)	9.650 Hour Full Range 79 • Interval 7.63 to 10.1	9.000 Hour Full Range 56 • Interval 7.67 to 10.0	—	—

SECONDARY outcome

Timeframe: Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)

Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for Tmax. Tmax was observed directly from data as time of first occurrence.