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DRUG:

Inqovi (decitabine/cedazuridine)

i
Other names: ASTX727, ASTX 727, oral C-DEC, DEC-C
Company:
Otsuka
Drug class:
DNMT inhibitor, Cytidine deaminase inhibitor
3d
Dose-Escalation Study of E7727, an Oral Cytidine Deaminase Inhibitor With Oral Decitabine in Subjects With Solid Tumors (clinicaltrials.gov)
P1, N=29, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jan 2024 --> Jun 2025
Trial completion date • Trial primary completion date
|
decitabine • Inqovi (decitabine/cedazuridine)
8d
Acute myeloid leukemia management and research in 2025. (PubMed, CA Cancer J Clin)
Since 2017, a turning point in AML research, 12 agents have received regulatory approval for AML in the United States: venetoclax (BCL2 inhibitor); gemtuzumab ozogamicin (CD33 antibody-drug conjugate); midostaurin, gilteritinib, and quizartinib (fms-like tyrosine kinase 3 inhibitors); ivosidenib, olutasidenib, and enasidenib (isocitrate dehydrogenase 1 and 2 inhibitors); oral azacitidine (a partially absorbable formulation); CPX351 (liposomal encapsulation of cytarabine:daunorubicin at a molar ratio of 5:1); glasdegib (hedgehog inhibitor); and recently revumenib (menin inhibitor; approved November 2024). Oral decitabine-cedazuridine, which is approved as a bioequivalent alternative to parenteral hypomethylating agents in myelodysplastic syndrome, can be used for the same purpose in AML. Menin inhibitors, CD123 antibody-drug conjugates, and other antibodies targeting CD123, CD33, and other surface markers are showing promising results. Herein, the authors review the frontline and later line therapies in AML and discuss important research directions.
Review • Journal • IO biomarker
|
FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD33 (CD33 Molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
Venclexta (venetoclax) • Xospata (gilteritinib) • Rydapt (midostaurin) • Vanflyta (quizartinib) • Tibsovo (ivosidenib) • Mylotarg (gemtuzumab ozogamicin) • Vyxeos (cytarabine/daunorubicin liposomal formulation) • Revuforj (revumenib) • Idhifa (enasidenib) • Inqovi (decitabine/cedazuridine) • Rezlidhia (olutasidenib) • Onureg (azacitidine oral) • Daurismo (glasdegib)
9d
KIT V560D-Mutated Systemic Mastocytosis Associated With High-Risk Myelodysplastic Syndrome: A Unique Case of Systemic Mastocytosis-Associated Hematologic Neoplasm. (PubMed, Case Rep Hematol)
We describe the clinical course and the outcome with the use of avapritinib, midostaurin, and decitabine-cedazuridine. Trial Registration: ClinicalTrials.gov identifier: NCT00782067.
Journal
|
KIT (KIT proto-oncogene, receptor tyrosine kinase)
|
KIT mutation • KIT V560D
|
Rydapt (midostaurin) • Ayvakit (avapritinib) • Inqovi (decitabine/cedazuridine)
14d
Oral Decitabine/Cedazuridine (DEC-C) in Combination With Nivolumab for Patients With Mucosal Melanoma (clinicaltrials.gov)
P1/2, N=8, Active, not recruiting, University of Colorado, Denver | Recruiting --> Active, not recruiting | N=30 --> 8
Enrollment closed • Enrollment change • Combination therapy • Checkpoint inhibition • IO biomarker • Checkpoint block • Metastases
|
CD4 (CD4 Molecule)
|
Opdivo (nivolumab) • Inqovi (decitabine/cedazuridine)
17d
ASTX727-06: A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose) (clinicaltrials.gov)
P2, N=332, Enrolling by invitation, Taiho Oncology, Inc. | Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Jan 2025 --> Dec 2025
Trial completion date • Trial primary completion date
|
Inqovi (decitabine/cedazuridine)
17d
ASTX727-03: Phase 1-2 Study of Low Dose ASTX727 (ASTX727 LD) in Lower Risk MDS (clinicaltrials.gov)
P1/2, N=160, Active, not recruiting, Taiho Oncology, Inc. | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
Trial completion date • Trial primary completion date
|
Inqovi (decitabine/cedazuridine)
1m
Decitabine/Cedazuridine and Enzalutamide for the Treatment of Metastatic Castrate Resistant Prostate Cancer (clinicaltrials.gov)
P1, N=8, Active, not recruiting, Roswell Park Cancer Institute | Recruiting --> Active, not recruiting | N=18 --> 8 | Trial completion date: Jan 2025 --> Mar 2026
Enrollment closed • Enrollment change • Trial completion date
|
TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1)
|
Xtandi (enzalutamide) • Inqovi (decitabine/cedazuridine)
2ms
NCI-2021-02246: Testing Oral Decitabine and Cedazuridine (ASTX727) in Combination With Venetoclax for Higher-Risk Acute Myeloid Leukemia Patients (clinicaltrials.gov)
P1/2, N=55, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2024 --> Oct 2025 | Trial primary completion date: Aug 2024 --> Oct 2025
Trial completion date • Trial primary completion date • Combination therapy • Tumor mutational burden
|
BCL2 (B-cell CLL/lymphoma 2)
|
Venclexta (venetoclax) • cytarabine • daunorubicin • Inqovi (decitabine/cedazuridine) • Starasid (cytarabine ocfosfate)
2ms
Enrollment change • Trial initiation date • Trial withdrawal
|
Inqovi (decitabine/cedazuridine) • beroterkib anhydrous (ASTX029)
3ms
STIMULUS MDS-US : Sabatolimab Added to HMA in Higher Risk MDS (clinicaltrials.gov)
P2, N=39, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed
Trial completion
|
azacitidine • decitabine • Inqovi (decitabine/cedazuridine) • sabatolimab (MBG453)
3ms
Enrollment change
|
Inqovi (decitabine/cedazuridine) • magrolimab (ONO-7913)
3ms
Oral decitabine/cedazuridine versus intravenous decitabine for acute myeloid leukaemia: A randomised, crossover, registration, pharmacokinetics study. (PubMed, Br J Haematol)
Next-generation sequencing was performed to identify molecular abnormalities that impact OS and TP53 mutations were associated with a poor outcome. These findings support the use of oral DEC-C in patients with AML.
PK/PD data • Journal
|
TP53 (Tumor protein P53)
|
TP53 mutation
|
Inqovi (decitabine/cedazuridine)
3ms
Current status and research directions in acute myeloid leukemia. (PubMed, Blood Cancer J)
Since 2017, twelve agents have been approved for the treatment of AML subsets: the BCL2 inhibitor venetoclax; the CD33 antibody drug conjugate gemtuzumab ozogamicin; three FLT3 inhibitors (midostaurin, gilteritinib, quizartinib); three IDH inhibitors (ivosidenib and olutasidenib targeting IDH1 mutations; enasidenib targeting IDH2 mutations); two oral hypomethylating agents (oral poorly absorbable azacitidine; fully absorbable decitabine-cedazuridine [latter approved as an alternative to parenteral hypomethylating agents in myelodysplastic syndrome and chronic myelomonocytic leukemia but commonly used in AML]); and CPX-351 (encapsulated liposomal 5:1 molar ratio of cytarabine and daunorubicin), and glasdegib (hedgehog inhibitor)...To achieve optimal results in such a rare and heterogeneous entity as AML requires expertise, familiarity with this rare cancer, and the access to, and delivery of disparate therapies under rigorous supportive care conditions. In this review, we update the standard-of-care and investigational therapies and outline promising current and future research directions.
Review • Journal • IO biomarker
|
FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD33 (CD33 Molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
IDH1 mutation • IDH2 mutation
|
Venclexta (venetoclax) • Xospata (gilteritinib) • azacitidine • Rydapt (midostaurin) • Vanflyta (quizartinib) • Tibsovo (ivosidenib) • Mylotarg (gemtuzumab ozogamicin) • Vyxeos (cytarabine/daunorubicin liposomal formulation) • Idhifa (enasidenib) • Inqovi (decitabine/cedazuridine) • Rezlidhia (olutasidenib) • Daurismo (glasdegib)
3ms
NCI-2021-00893: Decitabine/Cedazuridine and Venetoclax in Combination With Ivosidenib or Enasidenib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov)
P1/2, N=84, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025
Trial completion date • Trial primary completion date • Combination therapy
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
|
IDH2 mutation
|
Venclexta (venetoclax) • Tibsovo (ivosidenib) • Idhifa (enasidenib) • Inqovi (decitabine/cedazuridine)
3ms
Venetoclax and ASTX727 for the Treatment of Relapsed, Refractory, or Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov)
P2, N=100, Recruiting, M.D. Anderson Cancer Center | N=40 --> 100 | Trial completion date: Oct 2024 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2026
Enrollment change • Trial completion date • Trial primary completion date • Combination therapy
|
Venclexta (venetoclax) • Inqovi (decitabine/cedazuridine)
3ms
A Phase I-II Study Investigating the All Oral Combination of the Menin Inhibitor SNDX-5613 With Decitabine/Cedazuridine (ASTX727) and Venetoclax in Acute Myeloid Leukemia (SAVE) (clinicaltrials.gov)
P1/2, N=43, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026
Trial completion date • Trial primary completion date
|
Venclexta (venetoclax) • Revuforj (revumenib) • Inqovi (decitabine/cedazuridine)
4ms
Trial primary completion date
|
Venclexta (venetoclax) • azacitidine • decitabine • spartalizumab (PDR001) • Inqovi (decitabine/cedazuridine) • sabatolimab (MBG453)
4ms
ASTX727 and Dasatinib for the Treatment of Newly Diagnosed Philadelphia Chromosome or BCR-ABL Positive Chronic Myeloid Leukemia in Chronic Phase (clinicaltrials.gov)
P2, N=70, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Oct 2024 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2026
Trial completion date • Trial primary completion date
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
|
dasatinib • Inqovi (decitabine/cedazuridine)
4ms
STIMULUS MDS-US : Sabatolimab Added to HMA in Higher Risk MDS (clinicaltrials.gov)
P2, N=39, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2024 --> Oct 2024
Trial completion date
|
azacitidine • decitabine • Inqovi (decitabine/cedazuridine) • sabatolimab (MBG453)
5ms
Effect of Food on Blood Levels of ASTX727 (clinicaltrials.gov)
P1, N=18, Completed, Astex Pharmaceuticals, Inc. | Phase classification: P1b --> P1
Phase classification
|
Inqovi (decitabine/cedazuridine)
5ms
A Phase I/II Trial to Assess the Efficacy and Toxicity of ASTX727 (Oral Decitabine/Cedazuridine) for the Treatment of Hematological Neoplasms After Allogeneic Stem Cell Transplantation (clinicaltrials.gov)
P2, N=0, Withdrawn, M.D. Anderson Cancer Center | N=65 --> 0 | Trial completion date: Aug 2026 --> Jul 2024 | Not yet recruiting --> Withdrawn
Enrollment change • Trial completion date • Trial withdrawal
|
Inqovi (decitabine/cedazuridine)
5ms
Enrollment open • Enrollment change • Combination therapy
|
Venclexta (venetoclax) • Inqovi (decitabine/cedazuridine)
6ms
ASTX727 and Nivolumab in Squamous Cell Carcinoma of the Head and Neck (clinicaltrials.gov)
P1, N=0, Withdrawn, Case Comprehensive Cancer Center | N=15 --> 0 | Not yet recruiting --> Withdrawn
Enrollment change • Trial withdrawal • Metastases
|
Opdivo (nivolumab) • Inqovi (decitabine/cedazuridine)
6ms
Oral Decitabine/Cedazuridine (DEC-C) in Combination With Nivolumab for Patients With Mucosal Melanoma (clinicaltrials.gov)
P1/2, N=30, Recruiting, University of Colorado, Denver | Trial primary completion date: Jul 2024 --> Jul 2025
Trial primary completion date • Combination therapy • Checkpoint inhibition • IO biomarker • Checkpoint block • Metastases
|
CD4 (CD4 Molecule)
|
Opdivo (nivolumab) • Inqovi (decitabine/cedazuridine)
6ms
Decitabine/Cedazuridine and Enzalutamide for the Treatment of Metastatic Castrate Resistant Prostate Cancer (clinicaltrials.gov)
P1, N=18, Recruiting, Roswell Park Cancer Institute | Phase classification: P1b --> P1
Phase classification • Metastases
|
TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1)
|
Xtandi (enzalutamide) • Inqovi (decitabine/cedazuridine)
7ms
A Study Comparing Treatment Preference Between Oral Decitabine/Cedazuridine and Azacitidine in Myelodysplastic Syndrome, Low-Blast Acute Myeloid Leukemia, or Chronic Myelomonocytic Leukemia (clinicaltrials.gov)
P3, N=13, Active, not recruiting, Otsuka Australia Pharmaceutical Pty Ltd | Recruiting --> Active, not recruiting | N=42 --> 13 | Trial primary completion date: Apr 2025 --> Jan 2025
Enrollment closed • Enrollment change • Trial primary completion date
|
Inqovi (decitabine/cedazuridine) • Onureg (azacitidine oral)
7ms
STIMULUS MDS-US : Sabatolimab Added to HMA in Higher Risk MDS (clinicaltrials.gov)
P2, N=39, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=90 --> 39
Enrollment closed • Enrollment change
|
azacitidine • decitabine • Inqovi (decitabine/cedazuridine) • sabatolimab (MBG453)
7ms
Trial suspension • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
HER-2 negative
|
Keytruda (pembrolizumab) • paclitaxel • Inqovi (decitabine/cedazuridine)
7ms
Enrollment closed • Metastases
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
|
Inqovi (decitabine/cedazuridine) • Beleodaq (belinostat) • guadecitabine (SGI-110)
7ms
A dose determining trial to assess the recommended dose of ES-3000 and ASTX727 for patients with Myelodysplasia (ACTRN12621001713886)
P1/2, N=32, Recruiting, Australasian Leukaemia and Lymphoma Group | Not yet recruiting --> Recruiting
Enrollment open
|
Inqovi (decitabine/cedazuridine)
8ms
Phase classification
|
Inqovi (decitabine/cedazuridine)
8ms
Phase classification
|
Inqovi (decitabine/cedazuridine)
8ms
Trial completion date
|
Venclexta (venetoclax) • azacitidine • decitabine • spartalizumab (PDR001) • Inqovi (decitabine/cedazuridine) • sabatolimab (MBG453)
8ms
Enrollment open
|
BRCA (Breast cancer early onset)
|
Lynparza (olaparib) • Inqovi (decitabine/cedazuridine)
8ms
STIMULUS MDS-US : Sabatolimab Added to HMA in Higher Risk MDS (clinicaltrials.gov)
P2, N=90, Recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2025 --> Jun 2024 | Trial primary completion date: Jan 2024 --> Sep 2023
Trial completion date • Trial primary completion date
|
azacitidine • decitabine • Inqovi (decitabine/cedazuridine) • sabatolimab (MBG453)
8ms
Phase 1 Trial of ASTX727 in Subjects With Lower-risk Myelodysplastic Syndromes (clinicaltrials.gov)
P1, N=30, Active, not recruiting, Otsuka Pharmaceutical Co., Ltd. | Trial completion date: Dec 2023 --> Jan 2026 | Trial primary completion date: Dec 2023 --> Jan 2026
Trial completion date • Trial primary completion date
|
Inqovi (decitabine/cedazuridine)
8ms
ASTX727 and Nivolumab in Squamous Cell Carcinoma of the Head and Neck (clinicaltrials.gov)
P1, N=15, Not yet recruiting, Case Comprehensive Cancer Center
New P1 trial • Metastases
|
Opdivo (nivolumab) • Inqovi (decitabine/cedazuridine)
8ms
SOHO State of the Art Updates and Next Questions: An Update on Higher Risk Myelodysplastic Syndromes. (PubMed, Clin Lymphoma Myeloma Leuk)
There has been import of the IDH1 inhibitor ivosidenib, initially approved for AML; the Bcl-2 inhibitor venetoclax and liposomal daunorubicin/cytarabine (CPX-351) are under active investigation as well. Unfortunately, effective treatment of TP53-mutated disease remains elusive, though preliminary evidence suggests improved outcomes with oral decitabine/cedazuridine over parenteral hypomethylating agent monotherapy. Investigational agents with novel mechanisms of action may help expand the repertoire of treatment options for HR-MDS and trials continue to offer a hopeful therapeutic avenue for suitable patients.
Review • Journal • IO biomarker
|
TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
|
TP53 mutation
|
Venclexta (venetoclax) • Tibsovo (ivosidenib) • Vyxeos (cytarabine/daunorubicin liposomal formulation) • Inqovi (decitabine/cedazuridine)
9ms
Pharmacokinetics, Safety, and Efficacy of ASTX727 in Combination With Venetoclax in Acute Myeloid Leukemia (AML) (clinicaltrials.gov)
P1/2, N=188, Active, not recruiting, Astex Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting
Enrollment closed
|
Venclexta (venetoclax) • Inqovi (decitabine/cedazuridine)
9ms
Enrollment closed
|
Inqovi (decitabine/cedazuridine) • tolinapant (ASTX660)
9ms
ASTX727 in Recurrent/Progressive Non-enhancing IDH Mutant Gliomas (clinicaltrials.gov)
P1, N=18, Recruiting, Massachusetts General Hospital | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2022 --> May 2024
Trial completion date • Trial primary completion date
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
|
IDH2 mutation
|
Inqovi (decitabine/cedazuridine)