Phase 1
Completed 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
Source: ClinicalTrials.gov NCT01121575 ↗Enrolled (actual)
70
Serious AEs
44.3%
Results posted
Mar 2015
Primary outcomePrimary: Overview of Treatment-emergent All Causalities Adverse Events (AEs) in Escalation Phase — 14; 6; 7; 6 participants
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.
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 | — |
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. Informational only — not medical advice.