Phase 1
N=70
A Study Of Combined C- MET Inhibitor And PAN-HER Inhibitor (PF-02341066 And PF-00299804) In Patients With Non- Small Cell Lung Cancer
Non Small Cell Lung Cancer
Bottom Line
View on ClinicalTrials.gov: NCT01121575 ↗Enrolled (actual)
70
Serious AEs
44.3%
Results posted
Mar 2015
Primary outcome: Primary: Overview of Treatment-emergent All Causalities Adverse Events (AEs) in Escalation Phase — 14; 6; 7; 6 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- PF-02341066 (Drug); PF-00299804 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Pfizer
- Primary completion
- Feb 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overview of Treatment-emergent All Causalities Adverse Events (AEs) in Escalation Phase |
14; 6; 7; 6; 9; 4 | — |
| PRIMARY Overview of Treatment-emergent All Causalities AEs in Expansion Phase |
22; 11; 12; 8; 3; 2 | — |
| PRIMARY Overview of Treatment-emergent, Treatment-related AEs in Escalation Phase |
14; 6; 7; 6; 8; 3 | — |
| PRIMARY Overview of Treatment-emergent, Treatment-related AEs in Expansion Phase |
22; 11; 7; 6; 0; 0 | — |
| PRIMARY Number of Participants With Dose Limiting Toxicities (DLTs) in Escalation Phase |
0; 1; 0; 0; 0; 1 | — |
| SECONDARY Number of Participants With Stable Disease and Stable Disease Duration in Escalation Phase |
10; 3; 2; 5; 3; 2 | — |
| SECONDARY Number of Participants With Stable Disease and Stable Disease Duration in Expansion Phase |
6; 5; 1; 0; 4; 4 | — |
| SECONDARY Number of Participants With Objective Response Rate (ORR) in Escalation Phase |
0; 0; 0; 0 | — |
| SECONDARY Number of Participants With ORR in Expansion Phase |
1; 0 | — |
| SECONDARY Duration of Response for the Only Participant Shown Partial Response in Expansion Phase |
6.29 | — |
| SECONDARY Progression Free Survival (PFS) in Escalation Phase |
3.1; 3.0; 1.7; 4.4 | — |
| SECONDARY Progression Free Survival (PFS) in Expansion Phase |
2.1; 2.1 | — |
| SECONDARY Expression Analysis of Tumor Biomarkers (HGF, EGFR, and c-Met ) at Baseline Using Immunohistochemistry (IHC) Method |
40.0; 67.0; 193.2; 170.0; 125.0; 165.0 | — |
| SECONDARY Expression Analysis of Tumor Biomarkers (EGFR, and c-Met) at Baseline Using Fluorescent in Situ Hybridization (FISH) Method |
1.580; 1.180; 1.040; 1.000 | — |
| SECONDARY Number of Participants With c-Met, HER2, EGFR Amplification and ALK Rearrangement at Baseline Using FISH Method |
1; 0; 0; 0; 2; 3 | — |
| SECONDARY Plasma Concentration of sMet by Study Visits |
1353411.8; 1557000.0; 1519047.6; 1450500.0; 1483157.9; 1676666.7 | — |
| SECONDARY Number of Participants With EGFR Mutation at Baseline |
1; 1; 6; 3; 6; 3 | — |
| SECONDARY Number of Participants With KRAS Mutation (GLY12CYS) at Baseline |
1; 0 | — |
| SECONDARY Number of Participants With PIK3CA Mutation at Baseline |
1; 0; 1; 0; 2; 0 | — |
| SECONDARY Number of Participants With ROS1 Gene Translocation at Baseline |
0; 0 | — |
| SECONDARY 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) |
509.7; 420.8; 506.6; 656.6; 1759; 2464 | — |
| SECONDARY Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Area Under the Plasma Concentration-time Curve 10 (AUC10) |
624.9; 500.8; 559.6; 655.8; 2000; 2620 | — |
| SECONDARY Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Maximum Plasma Concentration (Cmax) |
84.24; 94.13; 90.86; 114.0; 231.5; 329.7 | — |
| SECONDARY Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Time of Last Quantifiable Concentration (Tlast) |
9.92; 9.33; 9.05; 9.75; 9.29; 9.42 | — |
| SECONDARY Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase -Time to Maximum Plasma Concentration (Tmax) |
3.00; 3.53; 3.92; 3.06; 1.68; 6.17 | — |
| SECONDARY Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUClast |
208.3; 132.3; 146.3; 307.7; 1339; 2343 | — |
| SECONDARY Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUC24 |
252.7; 347.9; 223.4; 306.6; 1336; 2334 | — |
| SECONDARY Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Cmax |
15.56; 17.49; 12.40; 18.22; 65.00; 122.4 | — |
| SECONDARY Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tlast |
24.0; 15.9; 23.6; 24.0; 24.00; 23.9 | — |
| SECONDARY Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tmax |
5.99; 8.03; 6.00; 6.17; 6.00; 5.09 | — |
| SECONDARY Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - AUClast |
2223; 1365; 616.3; 356.6 | — |
| SECONDARY Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - AUC10 |
2167; 1489; 634.3; 422.3 | — |
| SECONDARY Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Cmin |
181.8; 102.8; 47.22; 25.53 | — |
| SECONDARY Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Cmax |
306.0; 191.5; 82.92; 51.15 | — |
| SECONDARY Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Tlast |
9.650; 9.000; 9.650; 9.000 | — |
| SECONDARY Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Tmax |
2.04; 3.20; 3.96; 3.95 | — |
| SECONDARY Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - AUClast |
1016; 1148; 80.94; 78.22 | — |
| SECONDARY Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - AUC24 |
995.7; 1148; 78.57; 78.36 | — |
| SECONDARY Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Cmin |
33.11; 39.92; 5.440; 2.901 | — |
| SECONDARY Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Cmax |
47.15; 59.58; 4.222; 4.070 | — |
| SECONDARY Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Tlast |
24.40; 23.80; 24.50; 23.80 | — |
| SECONDARY Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Tmax |
16.0; 5.92; 5.90; 4.35 | — |
Summary
Lung cancer tumors become resistant to the first generation epidermal growth factor receptor (EGFR) inhibitors erlotinib or gefitinib by changing and increasing the activity of two cell signaling pathways: the cMET pathway and the EGFR pathway. Both resistance mechanisms can occur at the same time, in the same patient and even in the same tumor. This study combines a second generation EGFR inhibitor and a cMET inhibitor to block both these pathways in order to overcome resistance and treat this disease.
Eligibility Criteria
Inclusion Criteria
- advanced non small cell lung cancer (dose escalation phase)
- acquired resistance to erlotinib or gefitinib (expansion phase)
- mandatory entrance biopsy (expansion phase)
Exclusion Criteria
- interstitial lung disease
- unstable brain metastases
- leptomeningeal disease
Data sourced from ClinicalTrials.gov (NCT01121575). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.