Phase 1
Completed N=48
A Study Of PF-04449913 In Japanese Patients With Select Hematologic Malignancies
Source: ClinicalTrials.gov NCT02038777 ↗Enrolled (actual)
48
Serious AEs
42.6%
Results posted
Mar 2022
Primary outcomePrimary: Number of Participants With Dose-limiting Toxicities (DLTs): Monotherapy Cohort — 0; 0; 0 Participants
Summary
This is an open-label, multi-center, Phase 1 study of PF-04449913 in Japanese patients. PF-04449913 will be administered orally as a single agent in patients with select advanced hematologic malignancies, or in combination with LDAC [Low-Dose Ara-C] or cytarabine and daunorubicin in previously untreated patients with AML [Acute Myeloid Leukemia] or high-risk MDS [Myelodysplastic Syndrome], or in combination with azacitidine in previously untreated patients with AML.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose-limiting Toxicities (DLTs): Monotherapy Cohort |
0; 0; 0 | — |
| PRIMARY Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Monotherapy Cohort |
3; 4; 6; 1; 3; 1 | — |
| PRIMARY Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Abnormalities: Monotherapy Cohort |
0; 0; 0 | — |
| PRIMARY Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort |
0; 0; 0; 2; 4; 2 | — |
| PRIMARY Number of Participants With DLTs: Combination Cohort 1 |
— | — |
| PRIMARY Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 1 |
6; 1; 6; 4 | — |
| PRIMARY Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Abnormalities: Combination Cohort 1 |
— | — |
| PRIMARY Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1 |
0; 2; 2; 2; 1; 4 | — |
| PRIMARY Number of Participants With DLTs: Combination Cohort 2 |
1 | — |
| PRIMARY Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 2 |
6; 4; 6; 4 | — |
| PRIMARY Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Abnormalities: Combination Cohort 2 |
— | — |
| PRIMARY Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2 |
0; 0; 0; 6; 0; 1 | — |
| PRIMARY Percentage of Participants Achieving Disease Modifying Response (DMR): Expansion Cohort |
46.7 | <.0001 sig |
| PRIMARY Number of Participants With DLTs: Combination Cohort 3 |
— | — |
| PRIMARY Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 3 |
6; 1; 6; 5 | — |
| PRIMARY Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Abnormalities: Combination Cohort 3 |
— | — |
| PRIMARY Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3 |
0; 2; 1; 3; 0; 5 | — |
| SECONDARY Single Dose- Maximum Observed Plasma Concentration (Cmax) of PF-04449913: Monotherapy Cohort |
281.5; 321.1; 1019 | — |
| SECONDARY Single Dose- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04449913: Monotherapy Cohort |
1.970; 3.955; 1.950 | — |
| SECONDARY Single Dose- Terminal Plasma Half-life (T1/2) of PF-04449913: Monotherapy Cohort |
17.83; 30.70; 18.67 | — |
| SECONDARY Single Dose- Area Under the Plasma Concentration Curve: From Time Zero to End of Dosing Interval (AUCtau), From Time Zero to Last Quantifiable Concentration (AUClast) and From Time Zero to Infinity (AUCinf) of PF-04449913 for Monotherapy Cohort |
2413; 4499; 8843; 3255; 8911; 12750 | — |
| SECONDARY Single Dose- Clearance (CL/F) of PF-04449913: Monotherapy Cohort |
7.415; 5.210; 7.599 | — |
| SECONDARY Single Dose- Volume of Distribution (Vz/F) of PF-04449913: Monotherapy Cohort |
190.5; 227.8; 201.5 | — |
| SECONDARY Multiple Dose Cmax, Minimum Observed Plasma Concentration (Cmin), Average Observed Plasma Concentration (Cavg), Trough Plasma Concentration (Ctrough) of PF-04449913: Monotherapy Cohort |
356.9; 542.2; 1330; 84.94; 237.2; 333.9 | — |
| SECONDARY Multiple Dose- Tmax of PF-04449913: Monotherapy Cohort |
3.970; 4.000; 1.950 | — |
| SECONDARY Multiple Dose- AUCtau of PF-04449913: Monotherapy Cohort |
4561; 9299; 15480 | — |
| SECONDARY Multiple Dose- Clearance (CL/F) of PF-04449913: Monotherapy Cohort |
5.467; 5.369; 6.452 | — |
| SECONDARY Multiple Dose- Accumulation Ratio (Rac) of PF-04449913: Monotherapy Cohort |
1.893; 2.076; 1.752 | — |
| SECONDARY Multiple Dose- Steady State Accumulation Ratio (Rss) of PF-04449913: Monotherapy Cohort |
1.355; 1.017; 1.176 | — |
| SECONDARY Ratio of GLI1 Levels at Baseline to Day 21 Cycle 1: Monotherapy Cohort |
1.170; 1.588; 1.695 | — |
| SECONDARY Number of Participants With Best Response: Monotherapy Cohort |
0; 0; 1; 0; 0; 1 | — |
| SECONDARY Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 1 |
1172; 317.6; 648.3; 330.7; 1317; 341.6 | — |
| SECONDARY Multiple Dose- Tmax of PF-04449913: Combination Cohort 1 |
3.950; 1.935 | — |
| SECONDARY Multiple Dose- AUCtau of PF-04449913: Combination Cohort 1 |
15560; 16070 | — |
| SECONDARY Multiple Dose- CL/F of PF-04449913: Combination Cohort 1 |
6.428; 6.223 | — |
| SECONDARY Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Cytarabine: Combination Cohort 1 |
82.88; NA; 6.511; NA; 106.7; 0.5903 | — |
| SECONDARY Multiple Dose- Tmax of Cytarabine: Combination Cohort 1 |
0.2500; 0.2500 | — |
| SECONDARY Multiple Dose- T1/2 of Cytarabine: Combination Cohort 1 |
1.027; 0.8618 | — |
| SECONDARY Multiple Dose- AUCinf and AUCtau of Cytarabine: Combination Cohort 1 |
78.37; 77.97; 97.34; 97.58 | — |
| SECONDARY Multiple Dose- Cmax, Cmin, and Ctrough of Ara-uridine: Combination Cohort 1 |
371.6; 141.9; 141.9; 454.3; 201.7; 201.7 | — |
| SECONDARY Multiple Dose- Tmax of Ara-uridine: Combination Cohort 1 |
1.515; 2.000 | — |
| SECONDARY Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 2 |
1047; 318.2; 650.9; 354.0; 1181; 356.1 | — |
| SECONDARY Multiple Dose- Tmax of PF-04449913: Combination Cohort 2 |
5.950; 5.065 | — |
| SECONDARY Multiple Dose- AUCtau of PF-04449913: Combination Cohort 2 |
15630; 18120 | — |
| SECONDARY Multiple Dose- CL/F of PF-04449913: Combination Cohort 2 |
6.401; 5.523 | — |
| SECONDARY Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Daunorubicin: Combination Cohort 2 |
942.8; 2.589; 30.89; 2.673 | — |
| SECONDARY Multiple Dose- Tmax of Daunorubicin: Combination Cohort 2 |
0.3585 | — |
| SECONDARY Multiple Dose- T1/2 of Daunorubicin: Combination Cohort 2 |
7.297 | — |
| SECONDARY Multiple Dose- AUCinf and AUCtau of Daunorubicin: Combination Cohort 2 |
770.4; 741.6 | — |
| SECONDARY Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Daunorubicinol: Combination Cohort 2 |
244.4; 66.38; 116.7; 66.53 | — |
| SECONDARY Multiple Dose- Tmax of Daunorubicinol: Combination Cohort 2 |
0.3585 | — |
| SECONDARY Multiple Dose- AUCtau of Daunorubicinol: Combination Cohort 2 |
2800 | — |
| SECONDARY Ratio of GLI1 Levels at Baseline to Day 21 Cycle 1: Combination Cohort 1 |
1.835 | — |
| SECONDARY Ratio of GLI1 Levels at Baseline to Day 21 Cycle1: Combination Cohort 2 |
1.666 | — |
| SECONDARY Number of Participants With Best Response: Combination Cohort 1 |
1; 1; 2; 2 | — |
| SECONDARY Number of Participants With Best Response: Combination Cohort 2 |
3; 2; 2; 1; 2; 1 | — |
| SECONDARY Percentage of Participants With Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR: Combination Cohort 1 |
16.7; 16.7 | — |
| SECONDARY Duration of Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR Response: Combination Cohort 1 |
13.9; 15.3 | — |
| SECONDARY Time to Response: Combination Cohort 1 |
2.1; 0.8 | — |
| SECONDARY Overall Survival: Combination Cohort 1 |
11.8 | — |
| SECONDARY Overall Survival (OS): Expansion Cohort |
13.6 | — |
| SECONDARY Number of Participants With Best Response: Expansion Cohort |
6; 1; 0; 0; 1; 2 | — |
| SECONDARY Percentage of Participants With CR/CRi and DMR: Expansion Cohort |
46.7; 46.7 | — |
| SECONDARY Duration of Response: Expansion Cohort |
9.5; 10.1 | — |
| SECONDARY Time to Response: Expansion Cohort |
5.0; 2.3 | — |
| SECONDARY Ratio of GLI1 Levels at Baseline to Day 21 Cycle 1: Expansion Cohort |
0.905 | — |
| SECONDARY Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 3 |
1387; 414.1; 834.6; 526.3; 1218; 323.2 | — |
| SECONDARY Multiple Dose- Tmax of PF-04449913: Combination Cohort 3 |
4.000; 2.500 | — |
| SECONDARY Multiple Dose- AUCtau of PF-04449913: Combination Cohort 3 |
20010; 16860 | — |
| SECONDARY Multiple Dose- CL/F of PF-04449913: Combination Cohort 3 |
4.999; 5.936 | — |
| SECONDARY Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Azacitidine: Combination Cohort 3 |
1803; 1717; NA; 51.60; NA | — |
| SECONDARY Multiple Dose- Tmax of Azacitidine: Combination Cohort 3 |
0.2500; 0.2500 | — |
| SECONDARY Multiple Dose- AUCtau and AUCinf of Azacitidine: Combination Cohort 3 |
1200; 910.9; 1241; 1200 | — |
| SECONDARY Overall Survival: Combination Cohort 3 |
30.3 | — |
| SECONDARY Ratio of GLI1 Levels at Baseline to End of Treatment: Combination Cohort 3 |
0.776 | — |
| SECONDARY Number of Participants With Best Response: Combination Cohort 3 |
3; 1; 2 | — |
| SECONDARY Percentage of Participants With CR/CRi and DMR: Combination Cohort 3 |
50.0; 50.0 | — |
| SECONDARY Duration of Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR Response: Combination Cohort 3 |
6.6; 6.6 | — |
| SECONDARY Time to Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR Response: Combination Cohort 3 |
5.9; 5.8 | — |
| SECONDARY Number of Participants With Laboratory Test Abnormalities: Continuation Cohort |
— | — |
| SECONDARY Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Expansion Cohort |
15; 9; 14; 12 | — |
| SECONDARY Number of Participants With Clinically Significant Vital Signs: Expansion Cohort |
— | — |
| SECONDARY Number of Participants With Clinically Significant Vital Signs: Continuation Cohort |
— | — |
| SECONDARY Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Continuation Cohort |
1; 0; 1; 0 | — |
| SECONDARY Number of Participants With Laboratory Test Abnormalities: Expansion Cohort |
— | — |
Eligibility Criteria
Inclusion Criteria
- Patients with select advanced hematologic malignancies who are refractory, resistant or intolerant to prior therapies for monotherapy cohort.
- Patients with AML or High-Risk MDS who are newly diagnosed and previously untreated for combination cohort.
- Patients with AML who are newly diagnosed and previously untreated for azacitidine combination cohort.
- ECOG [Eastern Cooperative Oncology Group] performance status 0 to 2
- Adequate organ function
Exclusion Criteria
- Patients with active CNS disease
- Patient with active malignancy with the exception of basal cell carcinoma, non melanoma skin cancer, carcinoma in situ cervical
- Patient has an active, life threatening or clinically significant uncontrolled systemic infection
Data sourced from ClinicalTrials.gov (NCT02038777). 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.