Phase 1
Completed N=72
A Combination Study of PF-04449913 (Glasdegib) and Azacitidine In Untreated MDS, AML and CMML Patients
Source: ClinicalTrials.gov NCT02367456 ↗Enrolled (actual)
72
Serious AEs
72.2%
Results posted
Mar 2021
Primary outcomePrimary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Lead-in Cohort (LIC) — 12; 12; 8 Participants
Summary
This multi center open label Phase 1b study is designed to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of glasdegib (PF-04449913) when combined with azacitidine in patients with previously untreated Higher Risk Myelodysplastic Syndrome (MDS), Acute Myeloid Leukemia (AML), or Chronic Myelomonocytic Leukemia (CMML). This clinical study includes two components: (a) a safety lead in cohort (LIC) and (b) an expansion phase with an AML cohort and an MDS cohort.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Lead-in Cohort (LIC) |
12; 12; 8 | — |
| PRIMARY Number of Participants With Serious Adverse Events (SAEs) in the LIC |
9; 7 | — |
| PRIMARY Number of Participants With Laboratory Abnormalities in the LIC |
5; 12; 0; 8; 9; 3 | — |
| PRIMARY Percentage of Participants Achieving Complete Remission (CR) in the AML and MDS Cohorts |
20.0; 13.3 | — |
| SECONDARY Percentage of Participants Achieving Complete Remission (CR) + Partial Remission (PR) in the LIC |
25.0 | — |
| SECONDARY Number of Participants With Efficacy Measures Other Than CR in the LIC |
2; 4; 6 | — |
| SECONDARY Number of Participants With TEAEs in the AML and MDS Cohorts |
30; 30; 29; 29; 20; 25 | — |
| SECONDARY Number of Participants With SAEs in the AML and MDS Cohorts |
24; 19; 8; 9 | — |
| SECONDARY Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts |
0; 0; 30; 29; 0; 0 | — |
| SECONDARY Number of Participants With Disease-Specific Efficacy Measures in the AML Cohort |
0; 1; 2; 1; 6 | — |
| SECONDARY Number of Participants With Disease-Specific Efficacy Measures in the MDS Cohort |
3; 5; 8; 5; 1; 9 | — |
| SECONDARY Kaplan-Meier Estimate of Median Overall Survival (OS) in the AML and MDS Cohorts |
9.2; 17.8 | — |
| SECONDARY Duration of CR in the AML and MDS Cohorts |
5.78; 6.18 | — |
| SECONDARY Time to CR in the AML and MDS Cohorts |
5.54; 4.39 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort |
1013; 991.4 | — |
| SECONDARY Area Under the Plasma Concentration Curve From Time Zero to End of Dosing Interval (AUCtau) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort |
13230; 14350 | — |
| SECONDARY Time to First Occurrence of Maximum Plasma Concentration (Tmax) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort |
1.050; 1.500 | — |
| SECONDARY Cmax of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort |
778.5; 716.9 | — |
| SECONDARY Area Under the Plasma Concentration Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort |
1319; 1260 | — |
| SECONDARY Tmax of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort |
0.5000; 0.5000 | — |
| SECONDARY Trough Plasma Concentration (Ctrough) of Glasdegib on Cycle 1 Day 15 and Cycle 2 Day 1 in the AML and MDS Cohorts |
468.440; 308.144; 462.806; 167.483 | — |
| SECONDARY Number of Participants Meeting Categorical Criteria of QTcF Values in LIC, AML and MDS Cohorts |
5; 16; 17; 2; 6; 7 | — |
Eligibility Criteria
Inclusion criteria
- Patients must have previously untreated MDS, AML, or CMML according to the WHO 2016 classification.
- MDS patients must have Intermediate (>3 to 4.5 points), High Risk (>4.5 - 6) or Very High Risk (>6 points) disease according to the Revised International Prognostic Scoring System 2012 (IPSS-R).
- Clinical indication for treatment with azacitidine for MDS or AML.
Exclusion criteria
- Patients with AML who are candidates for standard induction chemotherapy as first line treatment.
- Patients with known active CNS leukemia.
- Prior treatment with a smoothened inhibitor (SMOi) and/or hypomethylating agent.
Data sourced from ClinicalTrials.gov (NCT02367456). 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.