Estybon (rigosertib) / Traws Pharma, Knight Therap, Specialised Therap, Pint Pharma - LARVOL DELTA

Efficacy of novel agents in the treatment of acute myeloid leukemia and myelodysplastic syndrome: A systematic review and meta-analysis (ASH 2025) - "Newer agents included for AML were Guadectiabine, Magrolimab, Alvocidib, Enasidenib, Flotetuzumab, Vadastuximab, Mitoxantrone, Pevonedistat, Entospletinib, Eprenetapopt, Belinostat, Onvansertib, Panobinostat, Cediranib Maleate, Nilotinib, Emavusertib, and anti-CD45 antibody (DOTA-BC8). The newer agents investigated for MDS included Rigosertib, Imetelstat, Pembrolizumab, Enasidenib, Sabatolimab, Ivosidenib, Elitercept, Pevonedistat, Emavusertib, Atezolizumab, and Olutasidenib...All patients were treated concomitantly with either azacitidine (77%) or decitabine (23%)... This meta-analysis and systematic review demonstrate promising efficacy for novel agents in AML and MDS patients. There is a need for prospective trials with larger patient populations to investigate these agents further."

Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • TP53

Targeting PLK1 in myelodysplastic syndromes: The Role of Rigosertib in Precision Medicine. (PubMed, Zhongguo Ying Yong Sheng Li Xue Za Zhi) - "Emerging evidence suggests rigosertib's potential in paediatric cancers like neuroblastoma and its synergy with therapies such as MEK inhibitors and hypomethylating agents. Future research should focus on optimizing combination strategies, identifying predictive biomarkers, and improving drug delivery to enhance its clinical efficacy and applicability across diverse cancer types."

Journal • Review • Acute Myelogenous Leukemia • Breast Cancer • Colorectal Cancer • Fatigue • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neuroblastoma • Oncology • Pancreatic Cancer • Pediatrics • Solid Tumor • PLK1

Multiomic Characterization of Myelodysplastic Neoplasms (MDS) with Micromegakaryocytes Highlights the Role of EZH2-RUNX1 deregulation in Disease Physiopathology and Response to Targeted Therapies (ASH 2023) - "Finally, activity of investigational drugs including 5-azacytidine, lenalidomide, venetoclax, rigosertib and pevonedistat, was evaluated in MEG01-activated cells and in vivo using a chicken embryo chorioallantoic membrane (CAM) model of MDS patient-derived xenograft (PDX). Thus, this phenomenon may be considered as a characteristic feature of MDS cases with an elevated proportion of micro-MK. Of note, preliminary in vitro and in vivo results support the use of venetoclax for the treatment of this subgroup of patients with dismal outcome."

Hematological Malignancies • Myelodysplastic Syndrome • Oncology • ASXL1 • DDX41 • ITGA2B • ITGB3 • RUNX1 • SF3B1 • SRSF2 • STAG2 • TET2 • U2AF1 • ZRSR2

Rigosertib in Patients With Recessive Dystrophic Epidermolysis Bullosa Associated SCC (clinicaltrials.gov) - P1 | N=3 | Completed | Sponsor: Thomas Jefferson University | Active, not recruiting ➔ Completed

Trial completion • Oncology • Squamous Cell Carcinoma

Rigosertib as a potential therapeutic option for patients with recessive dystrophic epidermolysis bullosa squamous cell carcinoma. (PubMed, Br J Dermatol) - No abstract available

Journal • Oncology • Squamous Cell Carcinoma

Unlocking the therapeutic potential of rigosertib as a selective therapy for ovarian cancer. (PubMed, Cell Rep Med) - "This approach identifies a small-molecule RAS mimetic, rigosertib, as a tumor-selective agent and leads us to identify the combination of rigosertib with phosphoinositide 3-kinase (PI3K) or mammalian target of rapamycin (mTOR) inhibition as effective combinations that prevent rigosertib-induced survival signaling while inducing regressions in ovarian cancer xenografts. These data support further exploration of these combinations for the treatment of ovarian cancer."

Journal • Oncology • Ovarian Cancer • Solid Tumor

CETSA-MS unveils novel targets engaged by rigosertib to promote anti-tumor activity and inflammatory responses. (PubMed, iScience) - "Moreover, rigosertib induced caspase-1 activation and gasdermin cleavage leading to Nod-like receptor pyrin domain-containing 3 (NLRP3)-dependent inflammatory responses in human lung cancer organoids. Our results suggest that rigosertib may effectively inhibit RAS-MAPK signaling and reprogram the tumor immune environment, presenting the potential for a potent therapeutic strategy in cancer treatment."

Journal • Lung Cancer • Oncology • Solid Tumor • ERO1A • GSDMC • NLRP3

EFFICACY AND OUTCOMES OF NOVEL THERAPEUTIC AGENTS AS MONOTHERAPY OR IN COMBINATION WITH CONVENTIONAL THERAPY IN MYELODYSPLASTIC SYNDROME: A SYSTEMATIC REVIEW AND META-ANALYSIS (EHA 2025) - "Newer agents included Rigosertib (41%, n=312/770), Imetelstat (15%, n=118/770), Pembrolizumab (8%, n=65/770), Enasidenib (9%, n=67/770), and Sabatolimab (7%, n=53/770) Ivosidenib (6%, 45/770), Elritercept 2%, n=15 /770), Pevonedistat (3%, 21/770), Emavusertib (2%, 15/770), Atezolizumab (6%, 46/770), and Olutasidenib (2%, n=13/770). The most commonly used conventional agent was azacitidine (19%, n= 147/770)... This study highlights promising results with the investigational agents for MDS. However, large studies with more power are needed to strengthen our understanding of these investigational agents in MDS patients."

Combination therapy • Monotherapy • Retrospective data • Review • Anemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia

Traws Pharma Announces Publication of Compelling Efficacy data in RDEB SCC Patients Treated with Legacy Oncology Drug Rigosertib (The Manila Times) - "The results indicated an overall response rate of 80%, with complete responses in 50% of evaluable patients."

Clinical data • Squamous Cell Skin Cancer

Efficacy and Safety of Rigosertib in Patients with Recessive Dystrophic Epidermolysis Bullosa Associated Advanced/Metastatic Cutaneous Squamous Cell Carcinoma. (PubMed, Br J Dermatol) - "These data identify rigosertib as a promising drug therapy for RDEB-SCC where there is a substantial unmet need, absence of approved therapies and where tumors arise on the background of a unique fibrotic and inflammatory environment characterized by germline mutations in COL7A1 that promote development of homogenous primary tumors with aberrant PLK1 activity."

Journal • Fibrosis • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • COL7A1

Multi-omic analysis of cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa (SID 2025) - P | "Omic signatures were analyzed through the LINCS drug repurposing database (NIH), identifying 6 potential therapeutic candidates, including rigosertib, which will be tested on primary SCC-AG cells and spheroids. This work aims to advance novel therapeutic strategies for SCC in RDEB patients."

Clinical • Omic analysis • Dermatology • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • COL7A1

Rigosertib in Patients With Recessive Dystrophic Epidermolysis Bullosa Associated SCC (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Thomas Jefferson University | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Squamous Cell Carcinoma

Unlocking therapeutic potential of rigosertib as a selective therapy for ovarian cancer (AACR 2025) - "Subsequent combination drug screening revealed a cooperative effect between rigosertib and PI3K inhibitor (taselisib), suggesting that combining rigosertib with taselisib which restricts mTOR activation enhances therapeutic efficacy. This combination showed synergy across ovarian cancer cell lines, organoids, and xenograft models, with xenograft studies showing a significant reduction in tumor burden. These findings highlight the potential of rigosertib, especially when paired with PI3K inhibitors, to target the unique mutational landscape of ovarian cancer, offering a promising direction for more effective treatments."

Oncology • Ovarian Cancer • Solid Tumor

STAG2 expression imparts distinct therapeutic vulnerabilities in muscle-invasive bladder cancer cells. (PubMed, Oncogenesis) - "We identified 100 total drug hits and found that STAG2 KO sensitized cells to treatment with PLK1 inhibitor rigosertib, whereas STAG2 KO protected cells from treatment with MEK inhibitor TAK-733 and PI3K inhibitor PI-103. Finally, synergy experiments revealed that berzosertib exhibits significant synergistic cytotoxicity in combination with cisplatin against MIBC cells. Altogether, our study presents evidence that berzosertib, PI-103, and the combination of berzosertib with cisplatin may be novel opportunities to investigate as precision medicine approaches for MIBC patients based on STAG2 tumor expression."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • STAG2

A Drosophila model for Costello Syndrome caused by Ras mutation K117R. (PubMed, bioRxiv) - "Ras pathway inhibitors Trametinib and Rigosertib suppressed the lethality but not the reduced size phenotypes. In contrast, the lack of effects on the reduced size phenotypes would be consistent with small stature resulting from Raf- and PI3K-independent processes. We propose that this model can be useful for future mechanistic analysis and pharmacological screening and evaluation."

Journal • CNS Disorders • Colorectal Cancer • Developmental Disorders • Mental Retardation • Oncology • Psychiatry • Solid Tumor • HRAS • KRAS • RAS

Inhibition of Polo-Like Kinase 1 Dampens the Replication of Vaccinia Virus in Mammalian Cells. (PubMed, J Med Virol) - "This study confirms the effects of the PLK1 inhibitors HMN-214 and ON-01910 on VACV replication in A549 cells. However, despite its strong in vitro effects, ON-01910 did not significantly reduce VACV replication in mice. These findings highlight the critical role of PLK1 in VACV replication and its potential as a target for antiviral therapy against orthopoxviruses."

Journal • Dermatology • Infectious Disease • PLK1

Polo-like Kinase 1 Inhibitors Demonstrate In Vitro and In Vivo Efficacy in Preclinical Models of Small Cell Lung Cancer. (PubMed, Cancers (Basel)) - P2 | "Rigosertib, volasertib, and onvansertib showed equivalent efficacy to that of standard care agents (irinotecan and cisplatin) in vivo with significant growth inhibition superior to cisplatin in PDX models of platinum-sensitive and platinum-resistant SCLC. We established the efficacy of PLK1 inhibitors in vitro and in vivo using PDX models of platinum-sensitive and resistant relapsed SCLC. An ongoing phase II trial is currently testing the efficacy of onvansertib in patients with SCLC (NCT05450965)."

Journal • Preclinical • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • FOXG1 • KDM5D • PLK1 • TP53 • YAP1

Polo-like Kinase 1 Inhibitors Demonstrate In Vitro and In Vivo Efficacy in Preclinical Models of Small Cell Lung Cancer (Multidisciplinary Digital Publishing Institute) - "Volasertib, rigosertib, and onvansertib showed strong in vitro cytotoxicity at nanomolar concentrations in human SCLC cell lines. Rigosertib, volasertib, and onvansertib showed equivalent efficacy to that of standard care agents (irinotecan and cisplatin) in vivo with significant growth inhibition superior to cisplatin in PDX models of platinum-sensitive and platinum-resistant SCLC."

Preclinical • Small Cell Lung Cancer

Osmotic stress influences microtubule drug response via WNK1 kinase signaling. (PubMed, Drug Resist Updat) - "In a genome-wide CRISPR-Cas9 resistance drug screen, we identified and validated the master osmostress regulator WNK1 kinase as a modulator of the response to the mitotic inhibitor rigosertib...This promotes resistance to microtubule depolymerizing compounds, and increased sensitivity to microtubule stabilizing drugs. In summary, our data proposes WNK1 osmoregulation activity as an important modulator for microtubule-associated chemotherapy response."

Journal • Oncology • WNK1

Rigosertib Plus Pembrolizumab in Treating Patients With Unresectable/Metastatic Melanoma Refractory to PD-1 Inhibitors (clinicaltrials.gov) - P2 | N=29 | Suspended | Sponsor: Vanderbilt-Ingram Cancer Center | Recruiting ➔ Suspended

Trial suspension • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF

Discovery of dual-targeted molecules based on Olaparib and Rigosertib for triple-negative breast cancer with wild-type BRCA. (PubMed, Bioorg Med Chem) - "Moreover, 13b displayed superior antitumor efficacy (TGI, 61.3 %) than the single administration of Ola (TGI, 38.5 %), 11b (TGI, 51.8 %) or even their combined administration (TGI, 56.7 %), but did not show significant systematic toxicity. These findings suggest that 13b may serve as a potential candidate for BRCA wild-type TNBC."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA

The construction of a prognostic model by apoptosis-related genes to predict survival, immune landscape, and medication in cholangiocarcinoma. (PubMed, Clin Res Hepatol Gastroenterol) - "Our project suggested that the prognostic model with apoptotic features can effectively predict prognosis in CCA patients, proffering prognostic biomarkers and potential therapeutic targets for CCA patients."

Journal • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor • MAP3K1

Drug screening in human physiologic medium identifies uric acid as an inhibitor of rigosertib efficacy. (PubMed, JCI Insight) - "Mechanistically, we found that the ability of rigosertib to destabilize microtubules is strongly inhibited by the purine metabolism end product uric acid, which is uniquely abundant in humans relative to traditional in vitro and in vivo cancer models. These results demonstrate the broad and dramatic effects nutrient levels can have on drug response, and how incorporation of human-specific physiological nutrient media might help to identify compounds whose efficacy could be impacted in humans."

Journal • Oncology

Rigosertib Plus Nivolumab for KRAS+ NSCLC Patients Who Progressed on First-Line Treatment (clinicaltrials.gov) - P1/2 | N=25 | Completed | Sponsor: Icahn School of Medicine at Mount Sinai | Recruiting ➔ Completed

Metastases • Trial completion • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Decoding cardiovascular risks: analyzing type 2 diabetes mellitus and ASCVD gene expression. (PubMed, Front Endocrinol (Lausanne)) - "Notably, RITA, ON-01910, doxercalciferol, and topiramate emerged as potential therapeutic agents for both T2DM and ASCVD, indicating their possible clinical significance. Our findings pinpoint ABCC5 and WDR7 as new target genes between T2DM and ASCVD, with RITA, ON-01910, doxercalciferol, and topiramate highlighted as promising therapeutic agents."

Journal • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Metabolic Disorders • Type 2 Diabetes Mellitus • ABCC5