This phase II trial studies the effect of belinostat and SGI-110 (guadecitabine) or ASTX727 in treating patients with conventional chondrosarcoma that cannot be removed by surgery (unresectable) and has spread from where it first started (primary site) to other places in the body (metastatic). Belinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as guadecitabine and ASTX727, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving belinostat in combination with guadecitabine or ASTX727 may lower the chance of unresectable and metastatic chondrosarcoma growing or spreading.

Start Date08 Sep 2020

Sponsor / Collaborator

National Cancer Institute

NCT04250246

/ Not yet recruitingPhase 2IIT

A Randomized, run-in, Multi-center, Phase II Study of Nivolumab Combined With Ipilimumab and Guadecitabine or Nivolumab Combined With Ipilimumab in Melanoma and NSCLC Patients Resistant to Anti-PD-1/PD-L1 (NIBIT-ML1)

This is a run-in, randomized, non-comparative, phase II study designed according to a two stages optimal design by Simon. This phase II design will be preceded by a safety evaluation after the first cohort of 6 patients to preserve a high-grade of overlapping and/or unexpected toxicity rate. The study will assess the immune-objective response rate (iORR) (assessed using iRECIST criteria) of nivolumab combined with ipilimumab and guadecitabine or nivolumab combined with ipilimumab, in Melanoma and non-small cell lung cancer (NSCLC) patients resistant to anti-PD-1/PD-L1 therapy. Immune biologic correlates to treatment will be assessed as exploratory endpoints.

Start Date01 Mar 2020

Sponsor / Collaborator

Bristol Myers Squibb Co.

[+1]

NCT03576963

/ WithdrawnPhase 1/2IIT

A Phase Ib/II Study of Guadecitabine (SGI-110) Plus Nivolumab in Refractory CIMP+ Metastatic Colorectal Cancer

This phase Ib/II trial studies the side effects and best dose of guadecitabine when given together with nivolumab and to see how well they work in treating participants with colorectal cancer that does not respond to treatment and has spread to other places in the body. Drugs used in chemotherapy, such as guadecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving guadecitabine and nivolumab may work better in treating participants with colorectal cancer.

Start Date30 Jan 2020

Sponsor / Collaborator

University of Southern California

[+3]

100 Clinical Results associated with Guadecitabine Sodium

100 Translational Medicine associated with Guadecitabine Sodium

100 Patents (Medical) associated with Guadecitabine Sodium

116

Literatures (Medical) associated with Guadecitabine Sodium

01 Aug 2026·Blood neoplasia

Bone marrow immunosuppressive states associate with survival after guadecitabine and atezolizumab therapy in HMA-R/R MDS

Article

Author: Sheridan, Rachael ; O'Connell, Casey L ; Burgos, Ryan S ; Wegener, Marc ; Johnson, Benjamin K ; Becker, Katelyn ; Triche, Timothy J ; Grønbæk, Kirsten ; Topper, Michael J ; Jang, H Josh ; Issa, Jean-Pierre J ; Youngblood, Benjamin A ; Nelson, Seth A ; Baer, Maria R ; Ørskov, Andreas Due ; Baylin, Stephen B ; Zebley, Caitlin C ; Givan, Scott A ; Lee, Hyein ; Adams, Marie ; Jones, Peter A ; Kim, Hyeon Jin ; Urrutia, Guillermo ; Nguyen, Anh Van ; Ramjan, Zachary H

Approximately half of patients with myelodysplastic syndromes (MDS) relapse or are refractory to hypomethylating agents (HMAs) and experience poor clinical outcomes. We previously reported improved survival in a phase 1/2 clinical trial combining the HMA guadecitabine with a programmed death-ligand 1 (PD-L1) inhibitor (atezolizumab) in HMA-relapsed or HMA-refractory (HMA-R/R) MDS, yet the biological features associated with durable responses to this combined epigenetic and immunotherapy approach remain unclear. Here, we performed integrated bulk and single-cell transcriptomic profiling of bone marrow samples from patients treated on this trial to identify molecular and cellular features associated with survival. Long-term survival was associated with the presence of immunosuppressive myeloid cells and primed dendritic cells at baseline, together with therapy-induced immune reinvigoration characterized by interferon pathway activation and expansion of effector lymphocytes. In contrast, short-term survival was associated with persistent senescence-associated inflammatory programs in CD34⁺ bone marrow cells and elevated expression of immunosuppressive immune checkpoint molecules. These findings suggest that chronic inflammatory and senescent microenvironmental states constrain effective immune activation despite combined epigenetic and immune checkpoint therapy. Here, we identify distinct bone marrow microenvironments associated with patient survival after combined epigenetic and immune checkpoint therapy and suggest candidate biomarkers to guide patient stratification in HMA-R/R MDS.

01 Feb 2025·LIFE SCIENCES

Hypomethylating agents as emerging therapeutics for triple-negative breast cancer

Review

Author: Mohd Redzwan, Norhanani ; Nik Amirah Auni, Nik Mohd Asri ; Yahya, Maya Mazuwin ; Fauzi, Agustine Nengsih ; Wong, Kah Keng

Triple-negative breast cancer (TNBC) is recognized as the most aggressive subtype of breast cancer. Epigenetic silencing, such as DNA methylation mediated by DNA methyltransferases (DNMTs) plays key roles in TNBC tumorigenesis. Hypomethylating agents (HMAs) such as azacitidine, decitabine, and guadecitabine are key inhibitors of DNMTs, and accumulating evidence has shown their immunogenicity properties. In this review, the efficacy and anti-tumor immune responses triggered by HMAs in TNBC are presented and discussed. Essentially, overexpression of DNMTs is associated with poor prognosis and reduced TNBC survival rates, and these effects are negated by HMAs. In particular, HMAs could reverse epigenetic silencing of tumor suppressor genes and enhance immune recognition of TNBC cells. Clinical trials of HMAs in TNBCs are limited but early-stage trials indicate that HMAs are safe and tolerable. More clinical studies are required to establish the effectiveness of HMAs against the disease, as supported by preclinical data substantiating their effectiveness especially guadecitabine. Future research should focus on optimizing dosing and exploring combinations with immunotherapies to maximize the potential of HMAs in TNBC treatment.

01 Jun 2024·Blood Neoplasia

Prospective performance of the IWG-2023 criteria and IPSS-M in a phase 2 trial of guadecitabine for higher-risk MDS or CMML

Article

Author: Prithviraj Bose ; Elias Jabbour ; Guillermo Garcia-Manero ; Naval Daver ; Samuel Urrutia ; Rashmi Kanagal-Shamanna ; Gautam Borthakur ; Courtney DiNardo ; Xuelin Huang ; Steven Kornblau ; Kristy Bodden ; Koichi Takahashi ; Yesid Alvarado ; Hagop Kantarjian ; Tapan Kadia ; Naveen Pemmaraju ; Farhad Ravandi

Guadecitabine (SGI-110) is a dinucleotide form of decitabine that has been studied in myelodysplastic syndrome (MDS) and acute myeloid leukemia. Here, we present the results of a single-center phase 2 trial of this agent for patients with higher-risk MDS or chronic myelomonocytic leukemia (CMML). Guadecitabine was administered at a dose of 60 mg/m2 subcutaneously for 5 days. Of 100 enrolled patients, 82% had MDS. The median age was 69 years, and International Prognostic Scoring System (IPSS) was intermediate-2 in 78% and high in 14%. Thirty-eight percent had complex cytogenetics, and 32% had TP53 ^mut . By the International Working Group 2006 (IWG-2006) criteria, 25% achieved complete remission (CR), 30% marrow CR, and 33% no response (NR). Common grade 3 events were febrile neutropenia (32%) and infection (25%). Mortality rates at 4 and 8 weeks were 0% and 4%, respectively. The median overall survival (mOS) was 16.8 months. Patients who underwent transplantation (21%) had an mOS of 46.6 months. We then reanalyzed this data set using IPSS-Molecular (IPSS-M) and IWG-2023 response criteria. By IPSS-M, 60% of patients were classified as very high and 27% as high risk. By IWG-2023, overall response rate was 52%, with 30% CR, 14% CR with limited count recovery, and 42% NR. IPSS-M provided adequate risk stratification at enrollment. Patients classified as marrow CR had widely different outcomes when reclassified by IWG-2023. In conclusion, SGI-110 was active in high-risk MDS, but survival is unlikely to be superior to current hypomethylating agents. The study is registered at www.ClinicalTrials.gov as #NCT02131597.

News (Medical) associated with Guadecitabine Sodium

27 Aug 2025

·moleculin.com

Moleculin Issues New Positive AML Overall Survival Data:

Median Overall Survival (OS) of 15 months for subjects with complete remission (n=8) Median OS of 2nd Line efficacy evaluable population of 12 months (n=9) Median OS of Intent to Treat population (1L-7L) of 9 months (n=22) OS demonstrated by Annamycin in the MB-106 trial is significantly above industry expectations for relapsed AML (4-6 months) Clinical study report anticipated in Q1 2026 Company continues to execute Part A of the pivotal MIRACLE Phase 3 trial HOUSTON, Aug. 27, 2025 (GLOBE NEWSWIRE) — Moleculin Biotech, Inc., (Nasdaq: MBRX) (“Moleculin” or the “Company”), a late-stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat cancers and viral infections, today announced the completion of its Phase 1B/2 (MB-106) clinical trial evaluating Annamycin in combination with Cytarabine (also known as “Ara-C” and for which the combination of Annamycin and Ara-C is referred to as AnnAraC) for the treatment of subjects with acute myeloid leukemia (AML). Database lock for the trial is expected by the end of September, with the final clinical study report (CSR) projected to be published in early Q1 2026. In total, 22 subjects were enrolled in the trial, with all subjects (1L-7L) who received AnnAraC per protocol having completed their efficacy evaluations (n=20). The updated overall survival (OS) data reveal the following: Median OS for Complete Remissions (CR): 15 months (n=8) with 4 subjects alive at study close Median OS for the intent to treat (ITT) Population (1L-7L): 9 months (n=22; 13 subjects experienced an event, 9 subjects censored) Median OS for 2L Efficacy Evaluable Population: 12 months (n=9) “Industry publications1 note that the typical OS for relapsed AML patients is roughly 4-6 months, these results highlight a remarkable improvement, exceeding expectations by 30% or more,” said Walter Klemp, Chairman and CEO of Moleculin Biotech. As previously reported, 8 subjects in the ITT population of 22 (36%) achieved a complete remission (CR) following treatment with AnnAraC. Among the subjects treated in the second line (2L) setting (n=10), the CR rate (the same primary efficacy endpoint as in the ongoing Phase 2B/3 pivotal MIRACLE trial), was 50%. Median durability for the 8 subjects achieving a CR was 10 months and continuing at the end of the study. CR durability ranged from 2 months to 22 months. CRs were achieved in subjects with a variety of prior treatments, including traditional 7+3 and venetoclax regimens. “We are glad to finally be in a position to close out our last Phase 2 AML trial, MB-106 by having completed follow-up on all subjects – some with durable CRs continuing – with database lock expected by the end of next month. While still technically preliminary, we are extremely pleased with the results of the MB-106 trial and look forward to the final CSR. These 2L data formed the basis for the design of the Phase 2B/3 pivotal MIRACLE trial with which we aim to gain eventual approval of Annamycin to serve the unmet need in 2L AML,” added Walter Klemp, Chairman and CEO of Moleculin. “We continue to see meaningful, positive trends across all data points, particularly in overall survival and durability. Of note, an 80+ yr old subject who achieved a CR with one cycle of Annamycin and then received two maintenance cycles of Annamycin finally relapsed after 600+ days. He then received a fourth round of Annamycin under compassionate use and is now back in remission. These data are very exciting and continue to give us hope that Annamycin has the potential to address the significant unmet need for safe and effective therapies for R/R AML. We also need to reemphasize that we have not seen any cardiotoxicity in any of the subjects to date, a key aspect of Annamycin.” “We can now also report that 50% of subjects achieving CR moved on to a curative bone marrow transplant, which is the most sought-after goal of any induction therapy in AML,” Mr. Klemp continued. “The results we have seen in 2L patients are better than any drug ever approved for second line AML and more than double the average for the last five drugs approved for 2L use.” “Looking ahead, we are focused on driving Part A of our Phase 3 MIRACLE trial forward and remain on track recruit the first 45 enrolled patients before the end of this year on which safety and efficacy will be unblinded. The final data from MB-106, coupled with the expected data from the MIRACLE trial will be invaluable as we continue to unlock the full potential of Annamycin for the treatment of AML,” concluded Mr. Klemp. The median age of subjects in MB-106 is 68 years. A total of 18 subjects had relapsed/refractory AML and 4 subjects were first line treatment. Two subjects discontinued early due to allergic reactions. All subjects who completed treatment had undergone post therapy disease response assessments (bone marrow assessment and/or peripheral blood evaluation) (Day 15 or later). No clinically significant signs of cardiotoxicity were noted during or after treatment in any of the subjects enrolled. The combination was well tolerated with myelosuppression and infections being the main adverse events (AEs). All data from MB-106 is preliminary and subject to change. Annamycin, also known by its non-proprietary name of naxtarubicin, currently has Fast Track Status and Orphan Drug Designation from the FDA for the treatment of relapsed or refractory acute myeloid leukemia, in addition to Orphan Drug Designation for the treatment of soft tissue sarcoma. Furthermore, Annamycin has Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia from the EMA. The Company is currently evaluating Annamycin in combination with Cytarabine (also known as “Ara-C” and for which the combination of Annamycin and Ara-C is referred to as “AnnAraC”) in a Phase 3 pivotal trial for the treatment of AML patients who are refractory to or relapsed after induction therapy (R/R AML). This global Phase 3 “MIRACLE” trial (derived from Moleculin R/R AML AnnAraC Clinical Evaluation) includes sites in the US, Europe and the Middle East. For more information about the MIRACLE trial, visit clinicaltrials.gov and reference identifier NCT06788756. Additionally, the clinical trial in the EU is on euclinicaltrials.eu and the reference identifier there is 2024-518359-47-00. 1 – Bruno C. Medeiros, Is there a standard of care for relapsed AML?, Best Practice & Research Clinical, Haematology, Volume 31, Issue 4, 2018, Pages 384-386, ISSN 1521-6926; Roboz GJ, Sanz G, et al. Guadecitabine vs TC in relapsed/refractory AML after intensive chemotherapy: a randomized phase 3 ASTRAL-2 trial. Blood Adv. 2024 Apr 23;8(8):2020-2029. doi: 10.1182/bloodadvances.2023012062. PMID: 38231126; PMCID: PMC11103175.; Faderl S, Wetzler M, et al. Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: results from the CLASSIC I Trial. J Clin Oncol. 2012 Jul 10;30(20):2492-9. doi: 10.1200/JCO.2011.37.9743. Epub 2012 May 14. PMID: 22585697; PMCID: PMC4874149. About Moleculin Biotech, Inc. Moleculin Biotech, Inc. is a Phase 3 clinical stage pharmaceutical company advancing a pipeline of therapeutic candidates addressing hard-to-treat tumors and viruses. The Company’s lead program, Annamycin, is a next-generation highly efficacious and well tolerated anthracycline designed to avoid multidrug resistance mechanisms and to lack the cardiotoxicity common with currently prescribed anthracyclines. Annamycin is currently in development for the treatment of relapsed or refractory acute myeloid leukemia (AML) and soft tissue sarcoma (STS) lung metastases. The Company has begun the MIRACLE (Moleculin R/R AML AnnAraC Clinical Evaluation) Trial (MB-108), a pivotal, adaptive design Phase 3 trial evaluating Annamycin in combination with cytarabine, together referred to as AnnAraC, for the treatment of relapsed or refractory acute myeloid leukemia. Following a successful Phase 1B/2 study (MB-106), with input from the FDA, the Company believes it has substantially de-risked the development pathway towards a potential approval for Annamycin for the treatment of AML. This study remains subject to appropriate future filings with potential additional feedback from the FDA and their foreign equivalents. Additionally, the Company is developing WP1066, an Immune/Transcription Modulator capable of inhibiting p-STAT3 and other oncogenic transcription factors while also stimulating a natural immune response, targeting brain tumors, pancreatic and other cancers. Moleculin is also engaged in the development of a portfolio of antimetabolites, including WP1122 for the potential treatment of pathogenic viruses, as well as certain cancer indications. For more information about the Company, please visit www.moleculin.com and connect on X, LinkedIn and Facebook. Forward-Looking Statements Some of the statements in this release are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995, which involve risks and uncertainties. Forward-looking statements in this press release include, without limitation, the timing of the MB-106 database lock for the trial and the publication of the final CSR, the timing of the release of the initial data on the first 45 subjects in the MIRACLE trial, and the Company’s ability to reconcile the US and EU MIRACLE protocols with the FDA and EMA, respectively. Moleculin will require significant additional financing, for which the Company has no commitments, in order to conduct its clinical trials as described in this press release, and the milestones described in this press release assume the Company’s ability to secure such financing on a timely basis. Although Moleculin believes that the expectations reflected in such forward-looking statements are reasonable as of the date made, expectations may prove to have been materially different from the results expressed or implied by such forward-looking statements. Moleculin has attempted to identify forward-looking statements by terminology including ‘believes,’ ‘estimates,’ ‘anticipates,’ ‘expects,’ ‘plans,’ ‘projects,’ ‘intends,’ ‘potential,’ ‘may,’ ‘could,’ ‘might,’ ‘will,’ ‘should,’ ‘approximately’ or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. These statements are only predictions and involve known and unknown risks, uncertainties, and other factors, including those discussed under Item 1A. “Risk Factors” in our most recently filed Form 10-K filed with the Securities and Exchange Commission (SEC) and updated from time to time in our Form 10-Q filings and in our other public filings with the SEC. Any forward-looking statements contained in this release speak only as of its date. We undertake no obligation to update any forward-looking statements contained in this release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events. Investor Contact:JTC Team, LLCJenene Thomas(908) 824-0775MBRX@jtcir.com

Clinical ResultPhase 3Orphan DrugFast TrackPhase 2

12 Apr 2021

·www.globenewswire.com

Global Acute Myeloid Leukemia (AML) Disease Analysis Report 2021: On Average, it Takes 10.8 Years from Phase I to Approval, Compared to 9.6 Years in the Overall Oncology Space

Dublin, April 12, 2021 (GLOBE NEWSWIRE) -- The "Disease Analysis: Acute Myeloid Leukemia (AML)" report has been added to ResearchAndMarkets.com's offering. AML is a type of heterogeneous hematological malignancy that originates from immature white blood cells (blasts) in the bone marrow, which may be derived from either a hematopoietic stem cell or a lineage-specific progenitor cell. "Acute" means that the leukemia may progress rapidly - AML generally spreads quickly to the bloodstream and can then spread to other parts of the body including the lymph nodes, spleen, central nervous system, and testicles.Latest Key TakeawaysThe publisher estimates that in 2018, there were 158,400 incident cases of acute myeloid leukemia (AML) worldwide and expects that number to increase to 169,000 incident cases by 2027. Approximately 60% of newly diagnosed patients are eligible for intensive chemotherapy, such as the 7+3 regimen of cytarabine and daunorubicin.Since 2017, there have been nine new drugs approved for AML in the US, dramatically changing the treatment landscape. Gone is the era where all front-line patients received either 7+3 chemotherapy or a hypomethylating agent (decitabine or azacitidine). Many of the new therapies target specific segments of AML or patients with specific mutations. As such, there is currently little competition between the new therapies, but that will change as therapies receive label expansions and new competitor therapies are approved.Two FLT3 inhibitors have been approved for FLT3-mutated AML: Rydapt for front-line patients eligible for intensive chemotherapy, and Xospata for relapsed/refractory patients. Rydapt may soon face competition in the front-line FLT3 setting as quizartinib, crenolanib, and Xospata are being evaluated in combination with standard chemotherapy and as single-agent maintenance therapies following either chemotherapy consolidation or hematopoietic stem cell transplant (HSCT). Approval in the lucrative maintenance setting would give these drugs a favorable long-term commercial outlook. Approximately 25-30% of AML patients have an FLT3 mutation.Tibsovo and Idhifa are approved in the US as oral, single-agent therapies for relapsed/refractory AML patients with IDH1 and IDH2 mutations, respectively. Tibsovo is also approved as a monotherapy for front-line patients over the age of 75 years. Both of these IDH inhibitors are now in Phase III trials in combination with standard induction (7+3) and consolidation chemotherapy and as maintenance therapy in front-line AML. Tibsovo is also being investigated in combination with azacitidine in a Phase III trial in front-line patients. Approval of Tibsovo and Idhifa in the EU will depend on these Phase III results. Tibsovo may face competition from FT-2102, an IDH1 inhibitor being evaluated in the relapsed/refractory setting in a pivotal single-arm Phase II trial. IDH1 mutations are present in 6-9% of AML, while IDH2 mutations are present in approximately 12% of cases.Mylotarg, an antibody-drug conjugate targeting CD33, is the only monoclonal antibody therapy approved for AML. Mylotarg combined with intensive chemotherapy is recommended for newly diagnosed patients with favorable cytogenetic risk (approximately 10% of patients eligible for intensive chemotherapy). Over 90% of AML patients are positive for CD33 expression.Vyxeos, a liposomal formulation of the 7+3 chemotherapy regimen, was approved in the US and EU for the treatment of newly diagnosed patients with secondary AML after showing an improvement in overall survival compared to the 7+3 regimen in patients ?60 years of age. Secondary AML accounts for approximately one third of new AML diagnoses, but most of these patients will be too frail for Vyxeos. Approximately 16% of patients eligible for intensive chemotherapy have secondary AML. Market access for Vyxeos is strengthened by positive recommendations from the US Centers for Medicare and Medicaid Services and from NICE in England and Wales.Venclexta combined with azacitidine is the new standard of care for newly diagnosed AML patients not suited for intensive chemotherapy (approximately 40% of newly diagnosed patients). A confirmatory Phase III trial evaluating Venclexta + azacitidine demonstrated a survival advantage (15 months versus 10 months) and supported regulatory submissions to European and Japanese authorities, with approvals expected in 2021. Venclexta is currently being evaluated in combination with novel agents in several trials, and a Phase III study (VIALE-M) is evaluating Venclexta combined with azacitidine as maintenance therapy for AML patients in first remission after conventional chemotherapy.Daurismo is the first and only Hedgehog pathway inhibitor approved for AML. Daurismo is approved in combination with low-dose cytarabine (LDAC) for newly diagnosed AML patients not suited for intensive chemotherapy, and will compete with Venclexta in this difficult-to-treat setting. However, in the US, hypomethylating agents are preferred over LDAC, so Venclexta may be preferred over Daurismo.Onureg, an oral formulation of azacitidine, increased overall survival and relapse-free survival in a Phase III trial and was approved in the US as a maintenance therapy following intensive chemotherapy for patients not suited for an HSCT. A European approval decision is expected in mid-2021. The maintenance setting would be a new setting for Vidaza (azacitidine) which is currently used in the EU (and off-label in the US) to treat newly diagnosed elderly AML patients.Rafael Pharmaceuticals is developing devimistat (CPI-613) as a first-in-class therapeutic targeting the altered mitochondrial metabolism present in many cancers, including AML. Devimistat's outlook will depend on the efficacy and safety results from a Phase III trial evaluating the drug in combination with high-dose cytarabine and mitoxantrone in relapsed/refractory AML patients. The first interim analysis is expected in Q2 2021.Chimerix's dociparstat sodium (DSTAT), a glycosaminoglycan analog of heparin designed to have reduced anticoagulant effects, targets the CXCR4 pathway which is involved in the homing and adhesion of AML cells to the bone marrow and is associated with resistance to systemic drugs. DSTAT is being developed in combination with intensive 7+3 chemotherapy for newly diagnosed AML, with the aim of improving the rate of durable response. A Phase III trial is enrolling patients with intermediate or unfavorable cytogenetic risk (74% of patients eligible for intensive chemotherapy).Otsuka's Inqovi is an oral formulation of decitabine that is being developed for patients with AML unsuited for intensive induction chemotherapy. In ASCERTAIN, a Phase III trial enrolling patients with MDS, Inqovi met the trial's primary endpoint of demonstrating pharmacokinetic equivalence to intravenous decitabine. ASCERTAIN has now been extended to include patients with AML in the EU, but a trial with efficacy endpoints will be needed to secure a US AML approval.Takeda's pevonedistat targets the NEDD8-activating enzyme in the ubiquitin-proteasome pathway, and is being developed in combination with azacitidine for a subpopulation of newly diagnosed, elderly AML patients categorized as low-blast count AML. Pevonedistat is also being evaluated in a randomized Phase II trial in combination with Venclexta and azacitidine in newly diagnosed AML patients unfit for intensive chemotherapy.Zeltherva is a therapeutic vaccine being developed as maintenance therapy for patients who have achieved hematologic complete remission, with or without thrombocytopenia, after second-line therapy and who are ineligible for allogeneic stem cell transplantation. Zeltherva's outlook in the specialized setting of CR2 will depend on results in REGAL, its Phase III trial. An interim analysis for safety and futility is expected in Q4 2021.Not including FLT3 and IDH inhibitors, there are five drugs in late-phase development for newly diagnosed AML patients. Dociparstat sodium and entospletinib are being developed in combination with intensive chemotherapy, while MBG453, pevonedistat, and Inqovi are being developed for elderly patients.Relapsed/refractory AML remains an area of unmet need, and new therapies are being developed. Not including FLT3 or IDH inhibitors, there are currently five late-stage therapies being evaluated for this setting (devimistat, DFP-10917, flotetuzumab, Iomab-B, and uproleselan).Key recent events include the approval of Onureg and presentation of numerical data from Venclexta's VIALE-A trial. There were Phase III failures for Helsinn's pracinostat combined with azacitidine in the newly diagnosed setting and for Roche's idasanutlin and Otsuka's guadecitabine in the relapsed/refractory setting. Other Phase III failures include trials evaluting Xospata combined with azacitidine and Daurismo combined with intensive chemotherapy in front-line AML, and an Idhifa monotherapy trial in the third- and fourth-line setting.Key upcoming catalysts for 2021 include topline results from Phase III trials for devimistat, Iomab-B, uproleselan, and Zeltherva, and a possible NDA submission for FT-2102.The overall likelihood of approval of a Phase I AML asset is 6.3%, and the average probability a drug advances from Phase III is 50%. AML drugs, on average, take 10.8 years from Phase I to approval, compared to 9.6 years in the overall oncology space. Companies Mentioned For more information about this report visit

AntibodyFirst in ClassVaccineADC

07 Jun 2019

·www.biospace.com

Astex Pharma and Otsuka’s Cancer Trial Meets Primary Endpoints

The fixed-dose combination was being evaluated in adults with intermediate and high-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Astex Pharmaceuticals , which is a member of the Otsuka group, and Otsuka Pharmaceutical announced that their ASCERTAIN Phase III clinical trial of cedazuridine and decitabine (ASTX727) compared to decitabine IV alone hit its primary endpoints. The fixed-dose combination was being evaluated in adults with intermediate and high-risk myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). The primary endpoint was decitabine exposure equivalence of five-day dosing between oral doses of the combination and the IV dose of decitabine. The company plans to submit a New Drug Application (NDA) for the combination therapy with the U.S. Food and Drug Administration (FDA) by the end of the year. “We are delighted with the outcome of the ASCERTAIN trial, and the demonstration that the fixed dose combination of cedazuridine with decitabine enables successful oral delivery of decitabine, alleviating the significant burden of five days of monthly IV infusions for patients who may continue to benefit from the drug for several months or even years,” stated Mohammad Azab, Astex’s president and chief medical officer. He added, “Subject to regulatory review and approvals, ASTX727 could bring a new treatment option to patients with these deadly diseases. We are extremely grateful to all the patients, caregivers, partner research and manufacturing organizations, as well as the healthcare professionals who contributed to this effort.” ASTX727 had been studied in a Phase I/II trial to determine appropriate doses for each component of the combination to determine that the decitabine dose in the oral formula is equivalent to that in IV decitabine at the approved daily dose of a one-hour infusion at 20 mg/m 2 . Also today, Taiho Oncology reported it has taken on commercialization responsibility from Otsuka Pharma for ASTX727, as well as guadecitabine (SGI-110) in the U.S. and Canada. Taiho Pharma Canada will commercialize them in Canada. “This commercialization agreement is highly significant for Taiho Oncology as it allows us to build on the long-term strategy of expanding our presence in North America,” stated Timothy Whitten, Taiho’s chief executive officer. “These investigational therapies have the potential to provide physicians and patients with much-needed treatment options for a range of hematologic malignancies. We look forward to working with Astex as we bring these compounds to market.” Astex is also currently conducting clinical trials with guadecitabine in relapsed and refractory acute myeloid leukemia (R/R AML) and relapsed and refractory myelodysplastic syndrome (R/R MDS) and CMML. Cedazuridine is a cytidine deaminase inhibitor, while decitabine is a DNA hypomethylating agent. ASTX727 inhibits cytidine deaminase in the gut and liver, which allows for the oral delivery of cedazuridine. Guadecitabine (SGI-110) is a DNA methyltransferase (DNMT) inhibitor. It was designed to be resistant to degradation by cytidine deaminase with the intention of increasing the exposure time of the active metabolite, decitabine, to cancer cells. That would allow decitabine to be absorbed in larger amounts by rapidly dividing cancer cells. It is being studied in combination with carboplatin to treat platinum-resistant ovarian cancer, in liver cancer after failure of Nexavar (sorafenib) and in combination with irinotecan for colorectal cancer.

NDAPhase 3License out/in

100 Deals associated with Guadecitabine Sodium

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic Myelomonocytic Leukemia	Phase 3	United States	Astex Pharmaceuticals, Inc.	13 Jan 2017
Chronic Myelomonocytic Leukemia	Phase 3	Japan	Astex Pharmaceuticals, Inc.	13 Jan 2017
Chronic Myelomonocytic Leukemia	Phase 3	Belgium	Astex Pharmaceuticals, Inc.	13 Jan 2017
Chronic Myelomonocytic Leukemia	Phase 3	Canada	Astex Pharmaceuticals, Inc.	13 Jan 2017
Chronic Myelomonocytic Leukemia	Phase 3	Czechia	Astex Pharmaceuticals, Inc.	13 Jan 2017
Chronic Myelomonocytic Leukemia	Phase 3	Denmark	Astex Pharmaceuticals, Inc.	13 Jan 2017
Chronic Myelomonocytic Leukemia	Phase 3	France	Astex Pharmaceuticals, Inc.	13 Jan 2017
Chronic Myelomonocytic Leukemia	Phase 3	Germany	Astex Pharmaceuticals, Inc.	13 Jan 2017
Chronic Myelomonocytic Leukemia	Phase 3	Italy	Astex Pharmaceuticals, Inc.	13 Jan 2017
Chronic Myelomonocytic Leukemia	Phase 3	Poland	Astex Pharmaceuticals, Inc.	13 Jan 2017

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04340843 (ETCTN/NCI 10330, CTgov)	Phase 2	Chondrosarcoma \| Central Nervous System Neoplasms \| Brain metastases	19	ASTX727+Belinostat (Treatment (Belinostat, ASTX727))	zjwatmpmtp = vsxakckqfs vhfbqvtvxn (hbkarrrhmp, oyioofdcgb - ggpmncelaj) View more	-	16 Sep 2025
				SGI-110+Belinostat (Treatment (Belinostat, SGI-110))	oxyryknytd = sbwlgybcxf knebiwxnqj (vyvftntghr, zlhfbjcvnc - xwribccrkq) View more
NCT02131597 (IWG-2023, CTgov)	Phase 2	High Risk Myelodysplastic Syndrome	100	Guadecitabine	alemtqclxf = ltelavadcp psserngwsc (gvngyvurnv, znxjbvuxtj - upjcvmduzj) View more	-	17 Jul 2025
NCT02131597 (IWG-2023, Pubmed)	Phase 2	Chronic Myelomonocytic Leukemia \| Myelodysplastic Syndromes	100	Guadecitabine 60 mg/m2	nfhlkhwuvq(ekercdwbha) = 32% aubwlurivj (qyqpzdolkz ) View more	Negative	01 Jun 2024
				guadecitabine (Transplantation)
NCT01896856 (Pubmed) Manual	Phase 2	Metastatic Colorectal Carcinoma	96	Guadecitabine anirinotecanan	uhhqxzolwi(qkbpmwbggo) = Common ≥Grade 3 treatment related adverse events in Arm A were neutropenia (42%), anemia (18%), diarrhea (11%), compared to Arm B pts with neutropenia (12%), anemia (12%). nxpdwrtegy (pumdfqbwmf ) View more	Positive	15 May 2024
				Regorafenib or TAS-102
NCT02920008 (ASTRAL-2, Pubmed) Manual	Phase 3	Acute Myeloid Leukemia	302	Guadecitabine	ceamuvwvhu(sosshwacri) = jecvyqirjd uehvdbtsqb (owbicqzmkz ) View more	Negative	17 Jan 2024
				Guadecitabine (Preselected treatment choice (TC))	ceamuvwvhu(sosshwacri) = pubapnaioi uehvdbtsqb (owbicqzmkz ) View more
NCT03913455 (CTgov)	Phase 2	Extensive stage Small Cell Lung Cancer	24	Carboplatin+Guadecitabine	uevvnkeqne = rziemdabcx aghxgyesjy (mcbfacifzb, lumxndoucf - subkwwngrj) View more	-	20 Dec 2023
Phase I/II clinical trial (ASH2023)	Phase 1/2	Chronic Myelomonocytic Leukemia \| Refractory Myelodysplastic Syndrome \| Recurrent Myelodysplastic Syndrome	27	Guadecitabine and Atezolizumab	amnmtoaojn(jdtkwxmrvq) = zegkuadosk vwknsvzbot (edgglcvace )	-	09 Dec 2023
NCT02348489 (Pubmed)	Phase 3	Acute Myeloid Leukemia	815	Guadecitabine	sueaewvlbj(wqdunlrbti) = bwpnbrlfmu xqtbjswlgq (wsypsozrvb ) View more	Negative	05 Jun 2023
				Treatment Choice (Azacitidine, Decitabine, or Low-dose Cytarabine)	sueaewvlbj(wqdunlrbti) = movflaqhvw xqtbjswlgq (wsypsozrvb ) View more
NCT04340843 (ETCTN/NCI 10330, ASCO2023) Manual	Phase 2	Chondrosarcoma IDH1/2 mutations	19	Belinostat + SGI-110	fjxrcapgiq(erxnfutfzm) = There were no objective responses zvdvqfedzg (hzgymptnaw ) View more	Positive	31 May 2023
				Belinostat + ASTX727
NCT02920008 (ASTRAL-2, CTgov)	Phase 3	Acute Myeloid Leukemia	302	guadecitabine (Guadecitabine)	ismqdxdrmq(gdhzfhumem) = xldrldhshp wtpbdheler (yggvgscbux, qrdcoinuza - hnxcfvjkwl) View more	-	25 May 2023
				Treatment Choice (TC) (Treatment Choice (TC))	ismqdxdrmq(gdhzfhumem) = xthbnwewtv wtpbdheler (yggvgscbux, pvwubknmdw - ynyjqkispt) View more

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