CBL0137 / Incuron, Statera BioPharma, Children's Oncology Group - LARVOL DELTA

PEPN2111: CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma (clinicaltrials.gov) - P1/2 | N=63 | Recruiting | Sponsor: Children's Oncology Group | Suspended ➔ Recruiting

Enrollment open • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • AFP

PEPN2111: CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma (clinicaltrials.gov) - P1/2 | N=63 | Suspended | Sponsor: Children's Oncology Group | Recruiting ➔ Suspended

Trial suspension • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • AFP

Development of orthotopic PDX models and discovery of targeted therapies in pediatric ependymoma (ISPNO 2026) - "Targeted agents were selected based on molecular alterations in relapsed zccs1304 tumors and assessed for therapeutic efficacy, including FACT inhibitor (CBL0137), NF-κB inhibitor (ACT001), VEGFR inhibitors (dovitinib, lenvatinib) and HDAC inhibitors (entinostat, quisinostat). Additionally, dovitinib in combination with CBL0137 or quisinostat significantly enhanced cytotoxicity in cultures. Our orthotopic ST-EPN PDX models offer a reliable preclinical platform for developing rational combination therapies for pediatric ST-EPN with ZFTA-RELA fusion."

Clinical • Ependymoma • Oncology • Pediatrics • Solid Tumor • RELA • ZFTA

Butyrylated PGAM5-Triggered and GSH-Responsive Cysteine Polymer Nanoparticles for CBL0137 Delivery to Enhance Necroptosis in Prostate Cancer. (PubMed, Adv Healthc Mater) - "This process promotes PGAM5 K95 butyrylation and strengthens necroptotic tumor cell killing. These results extend the design rationale of nanomedicine from passive payload transport toward active regulation of metabolism-dependent post-translational signaling in prostate cancer."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Inhibition of MCL-1-mediated anti-apoptotic signalling as a potential therapeutic strategy for paediatric high-grade gliomas (ISPNO 2026) - P1/2 | "Selective MCL-1 inhibitors (S63845, MIK665, BRD-810) and the BCL-2 inhibitor venetoclax were screened in cytotoxicity assays, with MIK665 showing the greatest efficacy against both HGG and DMG cells. The discovery that MCL-1 inhibition restores H3K27me3 reveals a novel mechanistic link between apoptotic evasion and epigenetic dysregulation. The robust synergy with epigenetic inhibitor CBL-0137 provides a compelling rationale for further preclinical development in DMG and HGG tumours."

IO biomarker • Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Glioma • High Grade Glioma • Mantle Cell Lymphoma • Pediatrics • Solid Tumor • ANXA5 • PDGFRA

The FACT complex associates with the RPA complex at viral replication compartments to promote adenovirus infection. (PubMed, J Virol) - "Inactivation of FACT by the curaxin, CBL0137, reduces Ad5 and Ad12 E1A-dependent induction of early gene products, while inhibition of FACT by siRNA similarly affected Ad5 gene product synthesis, but differentially affected Ad12 gene product expression...Identification and characterization of cellular, RPA complex-associated proteins at VRCs are important to understanding their multifaceted roles during infection. The studies described herein further our understanding of the relationship between adenovirus, the RPA complex, and VRCs during infection, establish proviral roles for the FACT complex, and identify FACT inhibitors as potential antivirals for adenovirus infection."

Journal • Infectious Disease • CDKN1A • SSRP1

Study of CBL0137 in Combination With Ipilimumab and Nivolumab Therapy in Melanoma (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Fox Chase Cancer Center | Trial completion date: Sep 2026 ➔ Sep 2027 | Trial primary completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Detecting phosphorylated MLKL in murine tissues. (PubMed, Methods Cell Biol) - "Phosphorylation of MLKL by RIPK3 is essential for the execution of necroptosis, and is thus a widely accepted biomarker for this mode of cell death. In this chapter, we describe our procedure for detecting phosphorylated murine MLKL in influenza A virus (IAV) infected lung tissues, and within tumors following treatment with the compound CBL0137."

Journal • Preclinical • Infectious Disease • Influenza • Oncology • Respiratory Diseases

Combined inhibition of FACT and BET disrupts transcription to suppress tumor growth in mouse models of diffuse midline glioma. (PubMed, Sci Transl Med) - "In vitro, a combinatorial therapeutic approach using the FACT inhibitor CBL0137, coupled with BET inhibition, revealed potent and synergistic cytotoxicity across a range of DMG cultures...This combination also elicited immune-related effects, including activation of the interferon response and antigen presentation mechanisms in DMG cells and induction of an activated state in macrophages and T cells, as demonstrated in an immunocompetent setting with spatial transcriptomics. Together, our data highlight the therapeutic promise of simultaneously targeting FACT and BET proteins in DMG, offering a dual tumor-intrinsic and immune-mediated strategy for combating this devastating pediatric brain tumor."

Journal • Preclinical • Brain Cancer • Diffuse Midline Glioma • Glioma • Oncology • Pediatrics • Solid Tumor • BRD4 • MDM4 • PDGFRA • SOX2

Chromatin remodeling with combined FACT and BET inhibition disrupts oncogenic transcription in Diffuse Midline Glioma (SNO 2025) - "In vitro, a combinatorial therapeutic approach using the FACT inhibitor CBL0137, coupled with BET inhibition revealed potent and synergistic cytotoxicity across a range of DMG cultures...Notably, this combination also elicited immune-related effects, including activation of the interferon response and antigen presentation in DMG cells and induction of an activated state in macrophages and T cells, as demonstrated in an immunocompetent setting using Xenium spatial profiling with a 5000 gene panel. Altogether, our data highlights the therapeutic promise of simultaneously targeting FACT and BET proteins in DMG, offering a dual tumor-intrinsic and immune-mediated strategy for combating this devastating pediatric brain tumor."

Brain Cancer • Diffuse Midline Glioma • Glioma • Solid Tumor • BRD4 • MDM4 • PDGFRA • SOX2

Chromatin remodeling with combined FACT and BET inhibition disrupts oncogenic transcription in Diffuse Midline Glioma (WFNOS 2025) - "In vitro, a combinatorial therapeutic approach using the FACT inhibitor CBL0137, coupled with BET inhibition revealed potent and synergistic cytotoxicity across a range of DMG cultures...Notably, this combination also elicited immune-related effects, including activation of the interferon response and antigen presentation in DMG cells and induction of an activated state in macrophages and T cells, as demonstrated in an immunocompetent setting using Xenium spatial profiling with a 5000 gene panel. Altogether, our data highlights the therapeutic promise of simultaneously targeting FACT and BET proteins in DMG, offering a dual tumor-intrinsic and immune-mediated strategy for combating this devastating pediatric brain tumor."

Brain Cancer • Diffuse Midline Glioma • Solid Tumor • BRD4 • MDM4 • PDGFRA • SOX2

Novel therapeutic development for aggressive variant prostate cancer (PCF 2025) - "Currently, in vivo cisplatin optimization and CBL0137–cisplatin combination therapy preclinical studies are being conducted. Funding Acknowledgement This research was supported by the U.S. Department of Defense CDMRP Prostate Cancer Research Program Idea Development Award (Number W81XWH-22-1-0571) and a PA Research Foundation Translational Research Innovation Award. Conflicts of Interest Disclosure Statement None to declare"

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR

CBL0137 as a promising therapeutic strategy for anaplastic, treatment-emergent neuroendocrine prostate cancer (AACR-NCI-EORTC 2025) - "Therefore, this study aims to assess the effect of CBL0137 as a novel targeted treatment for tNEPC, both as a monotherapy and as a co-therapy alongside the standard platinum-based chemotherapy, cisplatin and characterise the molecular consequences of CBL0137 by multi-omic profiling. The co-treatment consistently outperformed either drug alone, highlighting its potential as a more effective strategy for aggressive NEPC. Ongoing multi-omic profiling will further unravel the molecular consequences of CBL0137 treatment and support the development of improved therapeutic approaches for patients with anaplastic and treatment-resistant prostate cancer phenotypes."

Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor • CDKN1A

PEPN2111: CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma (clinicaltrials.gov) - P1/2 | N=63 | Recruiting | Sponsor: Children's Oncology Group | N=95 ➔ 63

Enrollment change • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • AFP

A phase 1 study of intra-arterial CBL0137 in extremity melanomas and sarcomas. (PubMed, Surg Oncol) - "The historic restrictions of standard regional therapies may be overcome with IA CBL0137, and this treatment is potentially applicable to a wide range of cancers beyond the extremities."

Journal • P1 data • Melanoma • Oncology • Sarcoma • Solid Tumor

A phase 1 trial of the FACT inhibitor CBL0137 in pediatric patients with relapsed or refractory solid and CNS tumors: A report from the Children's Oncology Group study PEPN2111. (ASCO 2025) - P1/2 | "The RP2D and MTD of CBL0137 in children and adolescents with solid or CNS tumors is 400mg/m2 IV weekly on Days 1 and 8 of 21-day cycles. CBL0137 leads to immune activation, with cytokine elevation and the possibility of CRS, an unexpected toxicity not previously reported in adults. A Phase 2 cohort in patients with Diffuse Midline Glioma is ongoing and includes further assessment of immune activation."

Clinical • P1 data • Anemia • Anorexia • Brain Cancer • Burkitt Lymphoma • CNS Tumor • Diffuse Midline Glioma • Ependymoma • Glioma • Hematological Malignancies • Hepatoblastoma • High Grade Glioma • Hypotension • Lymphoma • Neuroblastoma • Neutropenia • Oncology • Osteosarcoma • Pediatrics • Sarcoma • Thrombocytopenia • IL10 • IL1R1

Study of CBL0137 in Combination With Ipilimumab and Nivolumab Therapy in Melanoma (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Fox Chase Cancer Center | Trial completion date: Sep 2025 ➔ Sep 2026 | Trial primary completion date: Mar 2025 ➔ Mar 2026 | Suspended ➔ Recruiting

Enrollment open • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Enhancing Anti-PD-1 Immunotherapy by Targeting MDSCs via Hepatic Arterial Infusion in Breast Cancer Liver Metastases. (PubMed, Cancers (Basel)) - "Combination of CBL0137 HAI with PD-1 blockade improved survival in 4T1 tumors but not in CT26 tumors, and therapeutic efficacy relies on the finding of simultaneous and targeted depletion of myeloid-derived suppressor cells and skewing of T cell populations to produce synergy with PD-1 blockade therapy."

Journal • Breast Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Study of CBL0137 in Combination With Ipilimumab and Nivolumab Therapy in Melanoma (clinicaltrials.gov) - P1 | N=12 | Suspended | Sponsor: Fox Chase Cancer Center | Trial completion date: Sep 2024 ➔ Sep 2025 | Recruiting ➔ Suspended | Trial primary completion date: Mar 2024 ➔ Mar 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Trial suspension • Melanoma • Oncology • Solid Tumor

CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma (clinicaltrials.gov) - P1/2 | N=95 | Recruiting | Sponsor: Children's Oncology Group | Active, not recruiting ➔ Recruiting | N=38 ➔ 95

Enrollment change • Enrollment open • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Hematological Malignancies • Lymphoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • AFP

Study of CBL0137 in Combination With Ipilimumab and Nivolumab Therapy in Melanoma (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Fox Chase Cancer Center | Trial primary completion date: Nov 2024 ➔ Mar 2024

Combination therapy • Metastases • Trial primary completion date • Immune Modulation • Melanoma • Oncology • Solid Tumor

Study of CBL0137 in Combination With Ipilimumab and Nivolumab Therapy in Melanoma (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Fox Chase Cancer Center | Suspended ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Immune Modulation • Melanoma • Oncology • Solid Tumor

Study of CBL0137 in Combination With Ipilimumab and Nivolumab Therapy in Melanoma (clinicaltrials.gov) - P1 | N=12 | Suspended | Sponsor: Fox Chase Cancer Center | Not yet recruiting ➔ Suspended | Trial primary completion date: Mar 2024 ➔ Nov 2024

Combination therapy • Trial primary completion date • Trial suspension • Immune Modulation • Melanoma • Oncology • Solid Tumor

Study of CBL0137 in Combination With Ipilimumab and Nivolumab Therapy in Melanoma (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Fox Chase Cancer Center

Combination therapy • New P1 trial • Immune Modulation • Melanoma • Oncology • Solid Tumor

CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma (clinicaltrials.gov) - P1/2 | N=38 | Active, not recruiting | Sponsor: Children's Oncology Group | Recruiting ➔ Active, not recruiting

Enrollment closed • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Hematological Malignancies • Lymphoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • AFP