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

Large-scale drug screening identifies clinically actionable combinations to overcome BTK/PI3K inhibitor resistance in marginal zone lymphoma (AACR 2026) - "Here, we present data from a large pharmacological screen involving over 3,500 compounds in 2 MZL models with secondary resistance to BTK/PI3Ki, developed through prolonged exposure to idelalisib (Arribas 2022) or ibrutinib (Arribas 2025).Methods...Adding the alisertib (AURKAi), rigosertib (PLKi), fimepinostat (PI3K/HDACi), lanatoside-C (Na+K+ATPase), astragalin (apoptosis), astragaloside-I (WNT) and oridonin (AKT) was of benefit (additivity or synergism) in both parental and resistant cells.Conclusions...Several clinically advanced agents—particularly PAK4/NAMPT, AURKA, WNT, and Na⁺/K⁺-ATPase inhibitors—enhanced or restored the activity of BTKi/PI3Ki. These findings highlight new therapeutic strategies for relapsed/refractory MZL and support clinical evaluation of targeted combinations to overcome acquired resistance."

Clinical • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology • AURKA • NAMPT

IL-1-driven signaling promotes resistance to PI3K and BCL2 inhibitors in B-cell lymphoma preclinical models (AACR 2026) - "A 1,400-compound FDA-approved library was used in combination with copanlisib/venetoclax. VL51 cells with acquired resistance to PI3K/BCL2 inhibitors were characterized by an upregulation of IL1α and IL1β, elevated ERK and STAT3 phosphorylation, and increased expression of pro-survival and cytokine-responsive proteins. IL-1-driven reprogramming promotes resistance to PI3K and BCL2 inhibition in B-cell lymphoma via activation of NF-κB, STAT3, and metabolic survival pathways. Targeting IL-1 signaling or downstream effectors may overcome resistance and offer a promising therapeutic strategy for relapsed or refractory B-cell lymphomas."

IO biomarker • Preclinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ALDH1A1 • AURKA • IL1A • IL1B

Rigosertib for RDEB-SCC (clinicaltrials.gov) - P2 | N=12 | Not yet recruiting | Sponsor: Prof. Johann Bauer

New P2 trial • Oncology • Squamous Cell Carcinoma

Rigosertib for RDEB-SCC (clinicaltrials.gov) - P1/2 | N=12 | Recruiting | Sponsor: Prof. Johann Bauer

Trial completion date • Trial primary completion date • Oncology • Squamous Cell Carcinoma

Rigosertib for RDEB-SCC (clinicaltrials.gov) - P1/2 | N=12 | Recruiting | Sponsor: Prof. Johann Bauer | Phase classification: P2 ➔ P1/2

Phase classification • Oncology • Squamous Cell Carcinoma

Rigosertib for RDEB-SCC (clinicaltrials.gov) - P2 | N=12 | Recruiting | Sponsor: Prof. Johann Bauer | Trial completion date: Jun 2023 ➔ Jun 2026 | Trial primary completion date: Dec 2022 ➔ Dec 2025

Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Squamous Cell Carcinoma

Rigosertib for RDEB-SCC (clinicaltrials.gov) - P2 | N=12 | Recruiting | Sponsor: Prof. Johann Bauer | Trial completion date: Jun 2022 ➔ Jun 2023 | Trial primary completion date: Dec 2021 ➔ Dec 2022

Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Squamous Cell Carcinoma

Rigosertib for RDEB-SCC (clinicaltrials.gov) - P2 | N=12 | Recruiting | Sponsor: Prof. Johann Bauer | Trial completion date: Jun 2021 ➔ Jun 2022 | Trial primary completion date: Dec 2020 ➔ Dec 2021

Trial completion date • Trial primary completion date • Oncology • Squamous Cell Carcinoma

Rigosertib for RDEB-SCC (clinicaltrials.gov) - P2 | N=12 | Recruiting | Sponsor: Prof. Johann Bauer | Not yet recruiting ➔ Recruiting | Initiation date: May 2019 ➔ Sep 2019

Enrollment open • Trial initiation date • Oncology • Squamous Cell Carcinoma

Rigosertib for RDEB-SCC (clinicaltrials.gov) - P2 | N=12 | Not yet recruiting | Sponsor: Prof. Johann Bauer | Initiation date: Jan 2019 ➔ May 2019

Trial initiation date • Oncology • Squamous Cell Carcinoma

GPI inactivation mediates pentose phosphate pathway flux switch-on inducing temozolomide resistance in glioma stem cell. (PubMed, Cancer Lett) - "Targeting the ATM/PLK1/GPI axis through combinational treatment with rigosertib may therefore represent a therapeutic strategy. Moreover, PLK1 expression and GPI pT215 levels may serve as potential candidate markers for GBM. Collectively, activation of the ATM/PLK1/GPI axis plays a critical role in regulating PPP flux and TMZ resistance in GSCs."

Journal • Ataxia • Brain Cancer • Glioblastoma • Glioma • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Solid Tumor • GPI • PLK1

Rigosertib for RDEB-SCC (clinicaltrials.gov) - P1/2 | N=2 | Completed | Sponsor: Prof. Johann Bauer | Recruiting ➔ Completed | N=12 ➔ 2 | Trial completion date: Jun 2026 ➔ Dec 2025

Enrollment change • Trial completion • Trial completion date • Oncology • Squamous Cell Carcinoma

RAS/MEK/PI3K pathway inhibition augments response to CD40 agonism by targeting CD11b+ Bregs thereby overcoming melanoma PD1-resistance. (PubMed, Nat Commun) - "Here, we show that combined treatment with a RAS/PI3K/AKT-pathway inhibitor rigosertib (RGS), and/or a MEK1/2 inhibitor trametinib (T), plus aCD40, overcomes the ICB resistance of BRAFwtNRASwt and BRAFwtNRASmut melanoma tumors growing in C57BL/6 mice. scRNA-Seq analyses confirm CD40-associated CD11b+ Bregs across cancer types in patients. Our data demonstrate that addition of RAS/PI3K/AKT and MEK inhibitors to aCD40 resolves the issue of aCD40 induction of CD11b+PD-L1+ Bregs and provides alternative therapeutic options for ICB-resistant BRAFwtNRASwt or BRAFwtNRASmut metastatic melanoma."

IO biomarker • Journal • Melanoma • Oncology • Solid Tumor • CD40 • CD8 • ITGAM • PD-1 • PD-L1

Landscape targeted of therapy in advanced pancreatic adenocarcinoma: a network meta-analysis of randomized controlled trials [2010-2024]. (PubMed, J Gastrointest Oncol) - "The SUCRA rankings identified gemcitabine plus nimotuzumab (Gem-Nimot; 98%) as having the highest probability of ranking first for OS, followed by gemcitabine plus masitinib (Gem-Masit; 80%), gemcitabine plus erlotinib (Gem-Erlot; 70%), and gemcitabine plus sorafenib (Gem-Soraf; 23%). For PFS, Gem-Nimot (98%) ranked highest, followed by Gem-Erlot (73%), gemcitabine plus rigosertib (Gem-Rigos; 57%), and gemcitabine plus sunitinib (Gem-Sunit; 8%). This NMA combining network and forest plot results showed that Gem-Nimot provided significant survival benefits in advanced PA. EGFR-targeted combinations demonstrated a significant advantage in both OS and PFS compared with gemcitabine alone, indicating that EGFR inhibition may provide real clinical benefits."

Journal • Retrospective data • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

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