Head and Neck Neoplasms
Conditions
Keywords
recurrent or metastatic squamous cell cancer of the Head and Neck; no prior systemic therapy for recurrence
Brief summary
This study will investigate the safety and efficacy of oral PF-00299804 in patients who have not yet undergone any other drug treatment for recurrent and/ or metastatic head and neck squamous cell cancer.
Interventions
DRUGPF-00299804
45 mg by continuous oral dosing
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Recurrent or metastatic Squamous Cell Cancer of the Head and Neck; * Measurable disease; * Eastern Cooperative Oncology Group (ECOG) 0-1 in Stage 1 = first 23 patients; * Eastern Cooperative Oncology Group (ECOG) 0-2 in Stage 2 = 33 patients;
Exclusion criteria
* prior therapy for recurrence; * platelets \< 75,000; * prior Epidermal Growth Factor Receptor (EGFR) therapy; * interstitial lung disease; * primary of nasopharynx
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response (OR) of Complete Response (CR) or Partial Response (PR) | Baseline up to 18 months | Percentage of participants with best OR of confirmed CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST) relative to total number of evaluable participants for response. CR defined as disappearance of all target/non-target lesions. PR defined as at least a 30 percent (%) decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions. Confirmed responses (CR and PR) were those that persisted on a follow-up imaging assessment greater than or equal to (≥)4 weeks after the initial objective documentation of response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Stable Disease (SD) | Baseline up to 18 months | Time in weeks from start of treatment to date of objective disease progression (based on RECIST criteria). SD defined as neither sufficient shrinkage for PR nor sufficient increase for PD, taking as a reference the smallest sum of the longest dimensions since treatment start. Participants last known to be alive, not to have started new anticancer treatment, to be progression free, and who had a baseline and at least 1 on-study disease assessment were censored at date of last objective disease assessment that verified lack of PD. Participants who died not due to PD censored on death date. |
| Progression-Free Survival (PFS) | Baseline up to 18 months | Time in weeks from date of enrollment to first documentation of PD, death due to any cause, symptomatic deterioration, or start of secondary anticancer therapy, whichever occurred first. PFS calculated as (first event date minus enrollment date plus 1). Documentation of progression determined from objective disease assessment based on RECIST criteria. PD defined as at least a 20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since treatment started or the appearance of 1 or more new lesions. |
| Progression-Free Survival (PFS) at 6 Months and at 1 Year | Baseline up to 52 weeks | Probability of being event-free (event defined as PD, death due to any cause, symptomatic deterioration, or start of secondary anticancer therapy) at 26 weeks and 52 weeks after the first dose of study treatment. |
| Overall Survival (OS) | Baseline up to 18 months | Time in weeks from the start date of enrollment to date of death due to any cause. OS was calculated as (the death date minus the enrollment date plus 1). Participants without death dates, last known to be alive were censored at last contact. |
| Overall Survival at 6 Months and 1 Year | Baseline up to Week 52 | Probability of survival 26 weeks and 52 weeks after the first dose of study treatment. |
| Trough Plasma Concentrations (Ctrough) of Dacomitinib After Repeat Dosing | Predose on Day 1 of Cycles 2, 3, and 4 and predose on Day 8 of Cycle 1 | Trough concentrations of dacomitinib in plasma measured as nanograms per milliliter (ng/mL). |
| Ctrough of Dacomitinib After Repeat Dosing In Participants Requiring Administration of Dacomitinib With a Feeding Tube | Predose on Day 1 of Cycles 2, 3, and 4 and predose on Day 8 of Cycle 1 | — |
| Duration of Response (DR) | Baseline up to 18 months | Time in weeks from the first documentation of objective tumor response (CR or PR) to progression or death due to progressive disease (PD). DR was calculated as (the date of the first documentation of PD or death due to PD minus the date of the first CR or PR that was subsequently confirmed plus 1). DR was calculated for the subgroup of participants with a confirmed objective tumor response (CR or PR). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) In Participants Requiring Administration of Dacomitinib With a Feeding Tube | Cycle 1 Day 1 at predose and 1, 2, 4, 6, 8, 10, and 24 hours postdose | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) In Participants Requiring Administration of Dacomitinib With a Feeding Tube | Cycle 1 Day 1 at predose and 1, 2, 4, 6, 8, 10, and 24 hours postdose | — |
| Plasma Decay Half-Life (t1/2) | Cycle 1 Day 1 at predose and 1, 2, 4, 6, 8, 10, and 24 hours postdose | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Correlation Between Biomarkers Status and Best Overall Response | Baseline up to 18 months | The best overall response was best response recorded from the start of the treatment until disease progression/recurrence. In this outcome measure, biomarkers status and best overall response was reported in terms of correlation coefficient. |
| H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Baseline up to 18 Months | H-score is a measure of the immunohistochemistry staining positivity. The range for H-score is between 0 and 300. A higher score refers to stronger staining of a particular marker. |
| H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Baseline up to 18 Months | H-score is a measure of the immunohistochemistry staining positivity. The range for H-score is between 0 and 300. A higher score refers to stronger staining of a particular marker. |
| Maximum Observed Plasma Concentration (Cmax) In Participants Requiring Administration of Dacomitinib With a Feeding Tube | Cycle 1 Day 1 at predose and 1, 2, 4, 6, 8, 10, and 24 hours postdose | — |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dacomitinib 45 mg Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) received dacomitinib 45 milligram (mg) tablets, orally, once daily (QD) continuously until unacceptable toxicity, disease progression, withdrawal of consent, or death. There were no planned treatment breaks, each cycle was defined as 21 days for the purposes of scheduling. Dose reductions (in 15 mg increments) to a minimum of 15 mg QD were allowed; dose re-escalations were not allowed. | 69 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 57 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Other | 9 |
| Overall Study | Participant refused | 1 |
Baseline characteristics
| Characteristic | Dacomitinib 45 mg |
|---|---|
| Age, Continuous | 61.9 years STANDARD_DEVIATION 9 |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 68 / 69 |
| serious Total, serious adverse events | 20 / 69 |
Outcome results
Primary
Percentage of Participants With Objective Response (OR) of Complete Response (CR) or Partial Response (PR)
Percentage of participants with best OR of confirmed CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST) relative to total number of evaluable participants for response. CR defined as disappearance of all target/non-target lesions. PR defined as at least a 30 percent (%) decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions. Confirmed responses (CR and PR) were those that persisted on a follow-up imaging assessment greater than or equal to (≥)4 weeks after the initial objective documentation of response.
Time frame: Baseline up to 18 months
Population: Response-Evaluable Population: All participants with measurable disease (per RECIST), treated, with baseline and ≥1 on-study assessment. Participants who discontinued early before on-study tumor assessment due to PD were evaluable, but not if discontinued early due to reasons such as participant request, lack of compliance, or early toxicity.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dacomitinib 45 mg | Percentage of Participants With Objective Response (OR) of Complete Response (CR) or Partial Response (PR) | 12.5 Percentage of participants |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) In Participants Requiring Administration of Dacomitinib With a Feeding Tube
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Time frame: Cycle 1 Day 1 at predose and 1, 2, 4, 6, 8, 10, and 24 hours postdose
Population: PK Population; n=number of participants requiring administration of dacomitinib with a feeding tube.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dacomitinib 45 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) In Participants Requiring Administration of Dacomitinib With a Feeding Tube | 285.0 ng*hour (hr)/mL |
Secondary
Correlation Between Biomarkers Status and Best Overall Response
The best overall response was best response recorded from the start of the treatment until disease progression/recurrence. In this outcome measure, biomarkers status and best overall response was reported in terms of correlation coefficient.
Time frame: Baseline up to 18 months
Population: Biomarker analysis set: all enrolled participants who had baseline samples submitted as per Institutional Review Board/Independent Ethics Committee approval and participant consent. Here, number analyzed signifies participants evaluable at specific rows.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dacomitinib 45 mg | Correlation Between Biomarkers Status and Best Overall Response | HPV Overall Status | 0.799 Correlation coefficient |
| Dacomitinib 45 mg | Correlation Between Biomarkers Status and Best Overall Response | EGFR VIII Status with DNA Method | 1.000 Correlation coefficient |
| Dacomitinib 45 mg | Correlation Between Biomarkers Status and Best Overall Response | PTEN: | 0.840 Correlation coefficient |
| Dacomitinib 45 mg | Correlation Between Biomarkers Status and Best Overall Response | Mutation | 1.000 Correlation coefficient |
Secondary
Ctrough of Dacomitinib After Repeat Dosing In Participants Requiring Administration of Dacomitinib With a Feeding Tube
Time frame: Predose on Day 1 of Cycles 2, 3, and 4 and predose on Day 8 of Cycle 1
Population: PK population: all enrolled participants who received at least 1 dose of study medication from whom at least 1 PK sample was obtained. Here, Overall number of participants analyzed signifies participants evaluable for this outcome measure and number analyzed signifies participants evaluable for specific rows.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dacomitinib 45 mg | Ctrough of Dacomitinib After Repeat Dosing In Participants Requiring Administration of Dacomitinib With a Feeding Tube | Cycle 1 Day 8 | 81.30 ng/mL |
| Dacomitinib 45 mg | Ctrough of Dacomitinib After Repeat Dosing In Participants Requiring Administration of Dacomitinib With a Feeding Tube | Cycle 2 Day 1 | 92.05 ng/mL |
| Dacomitinib 45 mg | Ctrough of Dacomitinib After Repeat Dosing In Participants Requiring Administration of Dacomitinib With a Feeding Tube | Cycle 3 Day 1 | 129.2 ng/mL |
| Dacomitinib 45 mg | Ctrough of Dacomitinib After Repeat Dosing In Participants Requiring Administration of Dacomitinib With a Feeding Tube | Cycle 4 Day 1 | 156 ng/mL |
Secondary
Duration of Response (DR)
Time in weeks from the first documentation of objective tumor response (CR or PR) to progression or death due to progressive disease (PD). DR was calculated as (the date of the first documentation of PD or death due to PD minus the date of the first CR or PR that was subsequently confirmed plus 1). DR was calculated for the subgroup of participants with a confirmed objective tumor response (CR or PR).
Time frame: Baseline up to 18 months
Population: Response Evaluable population; n equals (=) number of participants with an objective response of CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dacomitinib 45 mg | Duration of Response (DR) | 17.9 weeks |
Secondary
Duration of Stable Disease (SD)
Time in weeks from start of treatment to date of objective disease progression (based on RECIST criteria). SD defined as neither sufficient shrinkage for PR nor sufficient increase for PD, taking as a reference the smallest sum of the longest dimensions since treatment start. Participants last known to be alive, not to have started new anticancer treatment, to be progression free, and who had a baseline and at least 1 on-study disease assessment were censored at date of last objective disease assessment that verified lack of PD. Participants who died not due to PD censored on death date.
Time frame: Baseline up to 18 months
Population: Response Evaluable population; n=number of participants with a best overall response of SD.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dacomitinib 45 mg | Duration of Stable Disease (SD) | 14.6 weeks |
Secondary
H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers
H-score is a measure of the immunohistochemistry staining positivity. The range for H-score is between 0 and 300. A higher score refers to stronger staining of a particular marker.
Time frame: Baseline up to 18 Months
Population: Biomarker analysis set: all enrolled participants who had baseline samples submitted as per Institutional Review Board/Independent Ethics Committee approval and participant consent. Here, Overall number of participants analyzed signifies participants evaluable for this outcome measures and number analyzed signifies participants evaluable at specific rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: AKT: at Cycle 1 Day 8 | 123.8 Score on a scale | Standard Deviation 77.83 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: CC3: at baseline | 22.1 Score on a scale | Standard Deviation 28.86 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: AKT: at baseline | 99.1 Score on a scale | Standard Deviation 77.9 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: CC3: at Cycle 1 Day 8 | 17.9 Score on a scale | Standard Deviation 27.41 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: EGFR: at baseline | 190.4 Score on a scale | Standard Deviation 113.11 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: EGFR: at Cycle 1 Day 8 | 184.4 Score on a scale | Standard Deviation 113.01 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: ERK: at baseline | 148.1 Score on a scale | Standard Deviation 74.26 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: ERK: at Cycle 1 Day 8 | 126.5 Score on a scale | Standard Deviation 63.8 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: HER2: at baseline | 36.8 Score on a scale | Standard Deviation 52.6 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: HER2: at Cycle 1 Day 8 | 43.0 Score on a scale | Standard Deviation 49.51 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: HER3: at baseline | 60.6 Score on a scale | Standard Deviation 62.49 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: HER3: at Cycle 1 Day 8 | 50.2 Score on a scale | Standard Deviation 42.41 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: pEGFR: at baseline | 101.2 Score on a scale | Standard Deviation 72.01 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: pEGFR: at Cycle 1 Day 8 | 115.6 Score on a scale | Standard Deviation 56.35 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: pEGFR: ratio to baseline | 1.0 Score on a scale | Standard Deviation 0.47 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: MET: at baseline | 70.0 Score on a scale | Standard Deviation 37.31 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: MET: at Cycle 1 Day 8 | 81.6 Score on a scale | Standard Deviation 54.84 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: pAKT: at baseline | 41.9 Score on a scale | Standard Deviation 51.71 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: pAKT: at Cycle 1 Day 8 | 31.4 Score on a scale | Standard Deviation 54.78 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: pERK: at baseline | 103.3 Score on a scale | Standard Deviation 46.36 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: pERK: at Cycle 1 Day 8 | 88.3 Score on a scale | Standard Deviation 41.51 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: pHER2: at baseline | 81.6 Score on a scale | Standard Deviation 31.79 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: pHER2: at Cycle 1 Day 8 | 78.5 Score on a scale | Standard Deviation 39.37 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: pMET: at baseline | 0.0 Score on a scale | Standard Deviation 0 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Cytoplasm: pMET: at Cycle 1 Day 8 | 0.0 Score on a scale | Standard Deviation 0 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Membrane: EGFR: at baseline | 258.3 Score on a scale | Standard Deviation 60.41 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Membrane: EGFR: at Cycle 1 Day 8 | 209.4 Score on a scale | Standard Deviation 99.88 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Membrane: HER2: at baseline | 8.2 Score on a scale | Standard Deviation 24.01 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Membrane: HER2: at Cycle 1 Day 8 | 4.3 Score on a scale | Standard Deviation 8.58 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Membrane: HER3: at baseline | 12.2 Score on a scale | Standard Deviation 27.29 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Membrane: HER3: at Cycle 1 Day 8 | 9.6 Score on a scale | Standard Deviation 16.09 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Membrane: MET: at baseline | 66.3 Score on a scale | Standard Deviation 71.26 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Membrane: MET: at Cycle 1 Day 8 | 53.9 Score on a scale | Standard Deviation 57.83 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Membrane: pEGFR: at baseline | 5.8 Score on a scale | Standard Deviation 14.27 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Membrane: pEGFR: at Cycle 1 Day 8 | 4.5 Score on a scale | Standard Deviation 7.27 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Membrane pHER2: at baseline | 1.6 Score on a scale | Standard Deviation 2.57 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Membrane pHER2: at Cycle 1 Day 8 | 5.8 Score on a scale | Standard Deviation 9.28 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Membrane: pMET: at baseline | 0.0 Score on a scale | Standard Deviation 0 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Membrane: pMET: at Cycle 1 Day 8 | 0.0 Score on a scale | Standard Deviation 0 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Nucleus: AKT: at baseline | 87.5 Score on a scale | Standard Deviation 67.31 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Nucleus: AKT: at Cycle 1 Day 8 | 111.8 Score on a scale | Standard Deviation 72.93 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Nucleus: ERK: at baseline | 152.3 Score on a scale | Standard Deviation 95.93 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Nucleus: ERK: at Cycle 1 Day 8 | 117.5 Score on a scale | Standard Deviation 73.69 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Nucleus: pAKT: at baseline | 40.6 Score on a scale | Standard Deviation 53.37 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Nucleus: pAKT: at Cycle 1 Day 8 | 19.1 Score on a scale | Standard Deviation 38.07 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Nucleus: pERK: at baseline | 152.7 Score on a scale | Standard Deviation 88.08 |
| Dacomitinib 45 mg | H-Score at Baseline and Post-baseline for Paired Biopsy Biomarkers | Nucleus: pERK: at Cycle 1 Day 8 | 144.8 Score on a scale | Standard Deviation 76.57 |
Secondary
H-Score at Ratio to Baseline for Paired Biopsy Biomarkers
H-score is a measure of the immunohistochemistry staining positivity. The range for H-score is between 0 and 300. A higher score refers to stronger staining of a particular marker.
Time frame: Baseline up to 18 Months
Population: Biomarker analysis set: all enrolled participants who had baseline samples submitted as per Institutional Review Board/Independent Ethics Committee approval and participant consent. Here, Overall number of participants analyzed signifies participants evaluable for this outcome measures and number analyzed signifies participants evaluable at specific rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Cytoplasm: AKT | 2.0 Ratio | Standard Deviation 3.03 |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Cytoplasm: CC3 | 1.0 Ratio | Standard Deviation 0.63 |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Cytoplasm: EGFR | 1.0 Ratio | Standard Deviation 0.17 |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Cytoplasm: ERK | 0.9 Ratio | Standard Deviation 0.29 |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Cytoplasm: HER2 | 0.7 Ratio | Standard Deviation 0.5 |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Cytoplasm: HER3 | 0.7 Ratio | Standard Deviation 0.6 |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Cytoplasm: pEGFR | 1.0 Ratio | Standard Deviation 0.47 |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Cytoplasm: MET | 1.2 Ratio | Standard Deviation 0.44 |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Cytoplasm: pAKT | 0.3 Ratio | Standard Deviation 0.28 |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Cytoplasm: pERK | 0.9 Ratio | Standard Deviation 0.35 |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Cytoplasm: pHER2 | 0.8 Ratio | Standard Deviation 0.42 |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Membrane: EGFR | 0.8 Ratio | Standard Deviation 0.33 |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Membrane: HER2 | 0.3 Ratio | — |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Membrane: HER3 | 0.6 Ratio | Standard Deviation 0.5 |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Membrane: MET | 0.8 Ratio | Standard Deviation 0.41 |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Membrane: pEGFR | 2.5 Ratio | Standard Deviation 4.33 |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Membrane pHER2 | 4.3 Ratio | Standard Deviation 4.5 |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Nucleus: AKT | 2.8 Ratio | Standard Deviation 4.73 |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Nucleus: ERK | 1.1 Ratio | Standard Deviation 1.38 |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Nucleus: pAKT | 0.3 Ratio | Standard Deviation 0.59 |
| Dacomitinib 45 mg | H-Score at Ratio to Baseline for Paired Biopsy Biomarkers | Nucleus: pERK | 0.9 Ratio | Standard Deviation 0.33 |
Secondary
Maximum Observed Plasma Concentration (Cmax) In Participants Requiring Administration of Dacomitinib With a Feeding Tube
Time frame: Cycle 1 Day 1 at predose and 1, 2, 4, 6, 8, 10, and 24 hours postdose
Population: PK Population; n=number of participants requiring administration of dacomitinib with a feeding tube.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dacomitinib 45 mg | Maximum Observed Plasma Concentration (Cmax) In Participants Requiring Administration of Dacomitinib With a Feeding Tube | 23.80 ng/mL |
Secondary
Overall Survival at 6 Months and 1 Year
Probability of survival 26 weeks and 52 weeks after the first dose of study treatment.
Time frame: Baseline up to Week 52
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dacomitinib 45 mg | Overall Survival at 6 Months and 1 Year | Survival Probability at Week 26 | 66.5 percent chance of survival |
| Dacomitinib 45 mg | Overall Survival at 6 Months and 1 Year | Survival Probability at Week 52 | 39.6 percent chance of survival |
Secondary
Overall Survival (OS)
Time in weeks from the start date of enrollment to date of death due to any cause. OS was calculated as (the death date minus the enrollment date plus 1). Participants without death dates, last known to be alive were censored at last contact.
Time frame: Baseline up to 18 months
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dacomitinib 45 mg | Overall Survival (OS) | 34.6 weeks |
Secondary
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Cycle 1 Day 1 at predose and 1, 2, 4, 6, 8, 10, and 24 hours postdose
Population: PK Population; n=number of participants requiring administration of dacomitinib with a feeding tube.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dacomitinib 45 mg | Plasma Decay Half-Life (t1/2) | NA hours |
Secondary
Progression-Free Survival (PFS)
Time in weeks from date of enrollment to first documentation of PD, death due to any cause, symptomatic deterioration, or start of secondary anticancer therapy, whichever occurred first. PFS calculated as (first event date minus enrollment date plus 1). Documentation of progression determined from objective disease assessment based on RECIST criteria. PD defined as at least a 20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since treatment started or the appearance of 1 or more new lesions.
Time frame: Baseline up to 18 months
Population: ITT Population: all enrolled participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dacomitinib 45 mg | Progression-Free Survival (PFS) | 12.1 weeks |
Secondary
Progression-Free Survival (PFS) at 6 Months and at 1 Year
Probability of being event-free (event defined as PD, death due to any cause, symptomatic deterioration, or start of secondary anticancer therapy) at 26 weeks and 52 weeks after the first dose of study treatment.
Time frame: Baseline up to 52 weeks
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dacomitinib 45 mg | Progression-Free Survival (PFS) at 6 Months and at 1 Year | Probability of being event free at Week 26 | 21.4 percent chance of being event free |
| Dacomitinib 45 mg | Progression-Free Survival (PFS) at 6 Months and at 1 Year | Probability of being event free at Week 52 | 2.1 percent chance of being event free |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) In Participants Requiring Administration of Dacomitinib With a Feeding Tube
Time frame: Cycle 1 Day 1 at predose and 1, 2, 4, 6, 8, 10, and 24 hours postdose
Population: PK Population; n=number of participants requiring administration of dacomitinib with a feeding tube.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dacomitinib 45 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) In Participants Requiring Administration of Dacomitinib With a Feeding Tube | 4.00 hours |
Secondary
Trough Plasma Concentrations (Ctrough) of Dacomitinib After Repeat Dosing
Trough concentrations of dacomitinib in plasma measured as nanograms per milliliter (ng/mL).
Time frame: Predose on Day 1 of Cycles 2, 3, and 4 and predose on Day 8 of Cycle 1
Population: Pharmacokinetic (PK) population: all enrolled participants who received at least 1 dose of study medication from whom at least 1 PK sample was obtained. Here, Overall number of participants analyzed signifies participants evaluable for this outcome measure and number analyzed signifies participants evaluable for specific rows.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dacomitinib 45 mg | Trough Plasma Concentrations (Ctrough) of Dacomitinib After Repeat Dosing | Cycle 1 Day 8 | 64.30 ng/mL |
| Dacomitinib 45 mg | Trough Plasma Concentrations (Ctrough) of Dacomitinib After Repeat Dosing | Cycle 2 Day 1 | 76.85 ng/mL |
| Dacomitinib 45 mg | Trough Plasma Concentrations (Ctrough) of Dacomitinib After Repeat Dosing | Cycle 3 Day 1 | 74.50 ng/mL |
| Dacomitinib 45 mg | Trough Plasma Concentrations (Ctrough) of Dacomitinib After Repeat Dosing | Cycle 4 Day 1 | 69.60 ng/mL |