Trial Outcomes & Findings for Safety and Efficacy of PF-299804 (Dacomitinib), a Pan-HER Irreversible Inhibitor, in Patients With Recurrent Glioblastoma With EGFR Amplification or Presence of EGFRvIII Mutation. A Phase II CT. (NCT NCT01520870)

Results Overview

Percentage of patients who have progressed / no progress after 6 months of treatment in each of the two cohorts.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

49 participants

Primary outcome timeframe

Baseline and after 6 months

Results posted on

2021-07-06

Participant Flow

This is a single-arm study. All patients received the same treatment: Dacomitinib 45 mg/day. To obtain a balanced population patients were enrolled in two cohorts depending on their EGFR mutational status. However, most endpoints and baseline characteristics are only analyzed for the full set population, as this was pre-especified per protocol and the interest of the study.

Patients with first recurrence were enrolled in 2 cohorts. Cohort A included patients with EGFR gene amplification without EGFRvIII mutation. Cohort B included patients with EGFR gene amplification and EGFRvIII mutation. All patients received Dacomitinib (45 mg/day) orally until disease progression/unacceptable adverse events (AEs)

Participant milestones

Participant milestones
Measure	PF-299804 (Dacomitinib) Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end. Patients at first recurrence will be enrolled onto 1 of 2 cohorts that will be recruited and analysed independently. Cohort A will include patients who have EGFRvIII mutations. Cohort B will include patients who have EGFR gene amplification but no EGFRvIII mutations. PF-299804 (Dacomitinib): Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end.
Overall Study STARTED	49
Overall Study COMPLETED	47
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	PF-299804 (Dacomitinib) Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end. Patients at first recurrence will be enrolled onto 1 of 2 cohorts that will be recruited and analysed independently. Cohort A will include patients who have EGFRvIII mutations. Cohort B will include patients who have EGFR gene amplification but no EGFRvIII mutations. PF-299804 (Dacomitinib): Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end.
Overall Study Withdrawal by Subject	2

Baseline Characteristics

Safety and Efficacy of PF-299804 (Dacomitinib), a Pan-HER Irreversible Inhibitor, in Patients With Recurrent Glioblastoma With EGFR Amplification or Presence of EGFRvIII Mutation. A Phase II CT.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PF-299804 (Dacomitinib) n=49 Participants Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end. Patients at first recurrence will be enrolled onto 1 of 2 cohorts that will be recruited and analysed independently. Cohort A will include patients who have EGFRvIII mutations. Cohort B will include patients who have EGFR gene amplification but no EGFRvIII mutations. PF-299804 (Dacomitinib): Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end.
Age, Continuous	59 years n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants
Region of Enrollment Spain	49 Participants n=5 Participants
MGMT methylation status MGMT methylated	10 Participants n=5 Participants
MGMT methylation status MGMT non-methylated	17 Participants n=5 Participants
MGMT methylation status not determined	22 Participants n=5 Participants
IDH1/2 mutational status IDH1 mutation	2 Participants n=5 Participants
IDH1/2 mutational status IDH 2 mutation	0 Participants n=5 Participants
IDH1/2 mutational status IDH1/2 non mutated	34 Participants n=5 Participants
IDH1/2 mutational status not determined	13 Participants n=5 Participants
ECOG performance status score 0	5 Participants n=5 Participants
ECOG performance status score 1	32 Participants n=5 Participants
ECOG performance status score 2	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and after 6 months

Population: Patients were analyzed stratified by cohorts according to their EGFR mutational status: Cohort A included patients with EGFR gene amplification without EGFRvIII mutation. Cohort B included patients with EGFR gene amplification and EGFRvIII mutation.

Percentage of patients who have progressed / no progress after 6 months of treatment in each of the two cohorts.

Outcome measures

Outcome measures
Measure	PF-299804 (Dacomitinib) n=47 Participants Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end. Patients at first recurrence will be enrolled onto 1 of 2 cohorts that will be recruited and analysed independently. Cohort A will include patients who have EGFRvIII mutations. Cohort B will include patients who have EGFR gene amplification but no EGFRvIII mutations. PF-299804 (Dacomitinib): Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end.
Progression-free Survival (PFS) at Six Months (PFS6m) Cohort A · No event	4 Participants
Progression-free Survival (PFS) at Six Months (PFS6m) Cohort A · Event (PFS previous to 6 months)	26 Participants
Progression-free Survival (PFS) at Six Months (PFS6m) Cohort B · Event (PFS previous to 6 months)	16 Participants
Progression-free Survival (PFS) at Six Months (PFS6m) Cohort B · No event	1 Participants

SECONDARY outcome

Timeframe: Up to 42 months

Population: Safety population. All patients that were enrolled and received at least 1 dose of study treatment

Type, incidence, severity, frequency, severity and relationship with IMP of reported adverse events, physical examinations and laboratory tests. Toxicity will be classified and tabulated by NCI-CTCAE v 4.0.

Outcome measures

Outcome measures
Measure	PF-299804 (Dacomitinib) n=49 Participants Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end. Patients at first recurrence will be enrolled onto 1 of 2 cohorts that will be recruited and analysed independently. Cohort A will include patients who have EGFRvIII mutations. Cohort B will include patients who have EGFR gene amplification but no EGFRvIII mutations. PF-299804 (Dacomitinib): Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end.
Safety and Tolerability of Oral Administration of PF-00299804. Any grade Adverse event · Yes	47 Participants
Safety and Tolerability of Oral Administration of PF-00299804. Any grade Adverse event · No	2 Participants
Safety and Tolerability of Oral Administration of PF-00299804. Grade 3 or higher Adverse envent · Yes	20 Participants
Safety and Tolerability of Oral Administration of PF-00299804. Grade 3 or higher Adverse envent · No	29 Participants

SECONDARY outcome

Timeframe: Baseline and every 12 weeks

Population: The analisis was stratified by cohort according to their EGFR mutational status

According to RANO criteria. Based on neurological symptoms, doses of dexamethasone and radiological response, assessed by the PI of each center. There will be central review of MRI.

Outcome measures

Outcome measures
Measure	PF-299804 (Dacomitinib) n=49 Participants Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end. Patients at first recurrence will be enrolled onto 1 of 2 cohorts that will be recruited and analysed independently. Cohort A will include patients who have EGFRvIII mutations. Cohort B will include patients who have EGFR gene amplification but no EGFRvIII mutations. PF-299804 (Dacomitinib): Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end.
Anti-tumor Response Cohort A · Stable disease	8 Participants
Anti-tumor Response Cohort A · Progressive disease	17 Participants
Anti-tumor Response Cohort A · Not evaluable	3 Participants
Anti-tumor Response Cohort A · Complete response	1 Participants
Anti-tumor Response Cohort A · Partial response	1 Participants
Anti-tumor Response Cohort B · Complete response	0 Participants
Anti-tumor Response Cohort B · Partial response	1 Participants
Anti-tumor Response Cohort B · Stable disease	4 Participants
Anti-tumor Response Cohort B · Progressive disease	13 Participants
Anti-tumor Response Cohort B · Not evaluable	1 Participants

SECONDARY outcome

Timeframe: Up to 42 months

Population: 2 patients were not evaluable because they withdrawn their consent Data is reported stratified by cohort according to their EGFR mutational status

Time from randomization to death by any cause.

Outcome measures

Outcome measures
Measure	PF-299804 (Dacomitinib) n=47 Participants Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end. Patients at first recurrence will be enrolled onto 1 of 2 cohorts that will be recruited and analysed independently. Cohort A will include patients who have EGFRvIII mutations. Cohort B will include patients who have EGFR gene amplification but no EGFRvIII mutations. PF-299804 (Dacomitinib): Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end.
Overall Survival (OS) Cohort A	7.8 Months Interval 5.6 to 10.1
Overall Survival (OS) Cohort B	6.7 Months Interval 4.3 to 9.1
Overall Survival (OS) Full data set	7.4 Months Interval 5.6 to 9.2

SECONDARY outcome

Timeframe: Baseline and every 12 weeks

Population: Data were not collected

Time from first objective response up to disease progression according RANO (in patients with objective responses).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and every 12 weeks

Population: Data were not collected

Percentage of patients decreasing doses of corticosteroids during treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and every 12 weeks

Population: Data were not collected

By means of minimental test, it will be determined the changes in neurological status of patients.

Outcome measures

Outcome data not reported

Adverse Events

PF-299804 (Dacomitinib)

Serious events: 16 serious events

Other events: 47 other events

Deaths: 43 deaths

Serious adverse events

Serious adverse events
Measure	PF-299804 (Dacomitinib) n=49 participants at risk Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end. Patients at first recurrence will be enrolled onto 1 of 2 cohorts that will be recruited and analysed independently. Cohort A will include patients who have EGFRvIII mutations. Cohort B will include patients who have EGFR gene amplification but no EGFRvIII mutations. PF-299804 (Dacomitinib): Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end.
Skin and subcutaneous tissue disorders Rash	22.4% 11/49 • Number of events 11 • Throughout the study period, 4 years Reported in the safety population, all patients that received at least one dose of study treatment (n= 49)
Gastrointestinal disorders Diarrhea	6.1% 3/49 • Number of events 3 • Throughout the study period, 4 years Reported in the safety population, all patients that received at least one dose of study treatment (n= 49)
General disorders Asthenia	4.1% 2/49 • Number of events 2 • Throughout the study period, 4 years Reported in the safety population, all patients that received at least one dose of study treatment (n= 49)

Other adverse events

Other adverse events
Measure	PF-299804 (Dacomitinib) n=49 participants at risk Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end. Patients at first recurrence will be enrolled onto 1 of 2 cohorts that will be recruited and analysed independently. Cohort A will include patients who have EGFRvIII mutations. Cohort B will include patients who have EGFR gene amplification but no EGFRvIII mutations. PF-299804 (Dacomitinib): Dacomitinib will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end.
Skin and subcutaneous tissue disorders Rash	81.6% 40/49 • Throughout the study period, 4 years Reported in the safety population, all patients that received at least one dose of study treatment (n= 49)
Gastrointestinal disorders Diarrhea	67.3% 33/49 • Throughout the study period, 4 years Reported in the safety population, all patients that received at least one dose of study treatment (n= 49)
General disorders Asthenia	22.4% 11/49 • Throughout the study period, 4 years Reported in the safety population, all patients that received at least one dose of study treatment (n= 49)
Gastrointestinal disorders Vomiting	8.2% 4/49 • Throughout the study period, 4 years Reported in the safety population, all patients that received at least one dose of study treatment (n= 49)

Additional Information

Pau Doñate

MFAR Clinical Research

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place