Presentation during EHA2026:All (e)Poster presentations will be made available as of until Thursday, June 11, 2026, 08:00 CEST and will be accessible for on-demand viewing from June 17 to October 15, 2026 on the Congress platform.
Abstract: EHA-3441 Short: PF671
Title: POOLED PHASE1/2 DATA IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES (MDS) AND MDS/MYELOPROLIFERATIVE NEOPLASMS SUPPORTS A BODY SURFACE AREA (BSA)-BASED DOSING STRATEGY FOR ORAL AZACITIDINE-CEDAZURIDINE
Type: Poster Presentation
Session title: Myelodysplastic syndromes - Clinical
Background:
The parenteral hypomethylating agent azacitidine (AZA) is a standard-of-care treatment for MDS and MDS/MPN overlap syndromes, including myelodysplastic type chronic myelomonocytic leukemia (CMML-MD). ASTX030 is an oral fixed-dose combination of AZA/cedazuridine (CED) developed to achieve systemic AZA exposure comparable to subcutaneous (SC) AZA. Phase (Ph) 2 pharmacokinetic (PK) results suggested the selection of a body surface area (BSA)–based dosing strategy for Ph 3 development.
Aims:
To report pooled safety, efficacy, and PK results from Ph1 and Ph2 of the ASTX030-01 study and further evaluate BSA-based dosing using a larger dataset.
Methods:
ASTX030-01 included an open-label Ph1 dose-finding study and a randomized, multicenter Ph2 crossover study in adult pts with MDS or MDS/MPN overlap syndromes eligible for AZA therapy. Ph1 evaluated multiple immediate- and delayed-release AZA/CED formulations to determine the recommended Ph2 dose (RP2D), with secondary objectives including safety, tolerability, PK/Pharmacodynamics, and efficacy. In Ph2, pts were randomized 1:1 to Sequence A or B. Sequence A received ASTX030 (140/20 mg) in C1, SC AZA (75 mg/m²) in C2, then ASTX030 from C3 onward; Sequence B received SC AZA in C1 and ASTX030 from C2 onward. The primary objective compared AZA AUC exposure between ASTX030 and SC AZA; secondary objectives included safety, PK, PD, and clinical responses.
The pooled analysis includes pts treated at approximate RP2D levels (136/20 and 144/20 mg) and Ph2 pts treated at RP2D (140/20 mg). Exploratory exposure–response analyses were planned to further characterize the relationship between AZA exposures and clinical outcomes.
Results:
As of January 2026, 57 pts (29 in Ph1; 28 in Ph2) including 45 with MDS, 8 with CMML, and 4 with other MDS/MPN. Median age was 72y and median treatment duration was 5.8 months. BSA distribution included 49% (n=28) intermediate (>1.55 and <2.15 m2), 44% (n=25) high (≥2.15 m2), and 7% (n=4) low (≤1.55 m2).
In Ph 2, ASTX030 oral AZA PK was comparable to SC AZA in the intermediate-BSA group with 140/20mg [Geometric mean ratio (GMR) of 0.98; 90% CI 0.85-1.13] but showed lower and higher exposures in high- and low- BSA groups, respectively. Pooled Ph1/2 PK equivalence analysis (n=56) showed GMR of 0.95 (90% CI 0.83-1.08).In pts with MDS, overall response rate (ORR) was 44.4% (20/45) per IWG 2006 criteria, with complete remission (CR) achieved in 20.0%. In pts with CMML or MDS/MPN, ORR was 33.3% (4/12) per IWG 2015, noting the limited size of this subgroup. With a median follow-up of 23.7 months, median progression-free survival was 23.1 months (95% CI, 12.9-NE), and median overall survival was not reached. Among red blood cell (RBC) transfusion–dependent pts at baseline, 31.8% achieved ≥8-week RBC transfusion independence.
Safety findings were consistent with the known AZA profile. Grade ≥3 adverse events (AEs) occurred in 89.5% of pts, most commonly neutropenia (33.3%), thrombocytopenia (31.6%), and anemia (29.8%). Common non-heme AEs were nausea (71.9%), constipation (68.4%), and fatigue (56.1%), mostly Grade 1 or 2.
Summary/Conclusion:
Pooled Ph1/2 data demonstrate that oral ASTX030 provides equivalent PK AUC exposures to SC AZA and a safety and efficacy profile consistent with that of SC AZA across a broad BSA range. Based on Ph2 PK data, a BSA-based dosing strategy was implemented for the ongoing global Ph3 AZTOUND study.
Clinical trial registration: NCT04256317
Keyword(s): MDS | Azacitidine | Myelodysplastic syndrome | Pharmacokinetic
Presentation during EHA2026:All (e)Poster presentations will be made available as of until Thursday, June 11, 2026, 08:00 CEST and will be accessible for on-demand viewing from June 17 to October 15, 2026 on the Congress platform.
Abstract: EHA-3441 Short: PF671
Title: POOLED PHASE1/2 DATA IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES (MDS) AND MDS/MYELOPROLIFERATIVE NEOPLASMS SUPPORTS A BODY SURFACE AREA (BSA)-BASED DOSING STRATEGY FOR ORAL AZACITIDINE-CEDAZURIDINE
Type: Poster Presentation
Session title: Myelodysplastic syndromes - Clinical
Background:
The parenteral hypomethylating agent azacitidine (AZA) is a standard-of-care treatment for MDS and MDS/MPN overlap syndromes, including myelodysplastic type chronic myelomonocytic leukemia (CMML-MD). ASTX030 is an oral fixed-dose combination of AZA/cedazuridine (CED) developed to achieve systemic AZA exposure comparable to subcutaneous (SC) AZA. Phase (Ph) 2 pharmacokinetic (PK) results suggested the selection of a body surface area (BSA)–based dosing strategy for Ph 3 development.
Aims:
To report pooled safety, efficacy, and PK results from Ph1 and Ph2 of the ASTX030-01 study and further evaluate BSA-based dosing using a larger dataset.
Methods:
ASTX030-01 included an open-label Ph1 dose-finding study and a randomized, multicenter Ph2 crossover study in adult pts with MDS or MDS/MPN overlap syndromes eligible for AZA therapy. Ph1 evaluated multiple immediate- and delayed-release AZA/CED formulations to determine the recommended Ph2 dose (RP2D), with secondary objectives including safety, tolerability, PK/Pharmacodynamics, and efficacy. In Ph2, pts were randomized 1:1 to Sequence A or B. Sequence A received ASTX030 (140/20 mg) in C1, SC AZA (75 mg/m²) in C2, then ASTX030 from C3 onward; Sequence B received SC AZA in C1 and ASTX030 from C2 onward. The primary objective compared AZA AUC exposure between ASTX030 and SC AZA; secondary objectives included safety, PK, PD, and clinical responses.
The pooled analysis includes pts treated at approximate RP2D levels (136/20 and 144/20 mg) and Ph2 pts treated at RP2D (140/20 mg). Exploratory exposure–response analyses were planned to further characterize the relationship between AZA exposures and clinical outcomes.
Results:
As of January 2026, 57 pts (29 in Ph1; 28 in Ph2) including 45 with MDS, 8 with CMML, and 4 with other MDS/MPN. Median age was 72y and median treatment duration was 5.8 months. BSA distribution included 49% (n=28) intermediate (>1.55 and <2.15 m2), 44% (n=25) high (≥2.15 m2), and 7% (n=4) low (≤1.55 m2).
In Ph 2, ASTX030 oral AZA PK was comparable to SC AZA in the intermediate-BSA group with 140/20mg [Geometric mean ratio (GMR) of 0.98; 90% CI 0.85-1.13] but showed lower and higher exposures in high- and low- BSA groups, respectively. Pooled Ph1/2 PK equivalence analysis (n=56) showed GMR of 0.95 (90% CI 0.83-1.08).In pts with MDS, overall response rate (ORR) was 44.4% (20/45) per IWG 2006 criteria, with complete remission (CR) achieved in 20.0%. In pts with CMML or MDS/MPN, ORR was 33.3% (4/12) per IWG 2015, noting the limited size of this subgroup. With a median follow-up of 23.7 months, median progression-free survival was 23.1 months (95% CI, 12.9-NE), and median overall survival was not reached. Among red blood cell (RBC) transfusion–dependent pts at baseline, 31.8% achieved ≥8-week RBC transfusion independence.
Safety findings were consistent with the known AZA profile. Grade ≥3 adverse events (AEs) occurred in 89.5% of pts, most commonly neutropenia (33.3%), thrombocytopenia (31.6%), and anemia (29.8%). Common non-heme AEs were nausea (71.9%), constipation (68.4%), and fatigue (56.1%), mostly Grade 1 or 2.
Summary/Conclusion:
Pooled Ph1/2 data demonstrate that oral ASTX030 provides equivalent PK AUC exposures to SC AZA and a safety and efficacy profile consistent with that of SC AZA across a broad BSA range. Based on Ph2 PK data, a BSA-based dosing strategy was implemented for the ongoing global Ph3 AZTOUND study.
Clinical trial registration: NCT04256317
Keyword(s): MDS | Azacitidine | Myelodysplastic syndrome | Pharmacokinetic