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

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 | "Clinical Trial Registration Number: NCT04870944 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • P1 data • Brain Cancer • CNS Tumor • Oncology • Pediatrics

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

CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma (clinicaltrials.gov) - P1/2 | N=38 | Recruiting | Sponsor: Children's Oncology Group | Not yet recruiting ➔ Recruiting | Trial primary completion date: Feb 2026 ➔ Dec 2026

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

CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma (clinicaltrials.gov) - P1/2; N=38; Not yet recruiting; Sponsor: Children's Oncology Group; Trial primary completion date: Dec 2026 ➔ Feb 2026

Clinical • Trial primary completion date • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Hematological Malignancies • Lymphoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • AFP

CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma (clinicaltrials.gov) - P1/2; N=38; Not yet recruiting; Sponsor: Children's Oncology Group; Initiation date: Sep 2021 ➔ Dec 2021

Clinical • Trial initiation date • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Hematological Malignancies • Lymphoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • AFP

[VIRTUAL] Results of a completed phase I trial of CBL0137 administered intravenously (IV) to patients (Pts) with advanced solid tumors. (ASCO 2020) - P1 | "Nausea and vomiting were successfully prevented with dexamethasone/serotonin antagonists. CBL0137 administered IV was generally well tolerated with manageable toxicities The MTD and RP2D were estimated at 540 mg/m2 due to myelosuppressive DLTs. PK were predictable. Preliminary evidence of antitumor activity supports Phase 2 testing."

Clinical • P1 data • Brain Cancer • Cardiovascular • Gastrointestinal Cancer • Genito-urinary Cancer • Glioblastoma • Gynecologic Cancers • Hematological Disorders • Hepatocellular Cancer • Liver Cancer • Neutropenia • Oncology • Prostate Cancer • Solid Tumor • Thrombocytopenia • Thrombosis • Uterine Cancer • Venous Thromboembolism

CBL0137 for the Treatment of Relapsed or Refractory Solid Tumors, Including CNS Tumors and Lymphoma (clinicaltrials.gov) - P1/2; N=4; Not yet recruiting; Sponsor: Children's Oncology Group

Clinical • New P1/2 trial • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Hematological Malignancies • Lymphoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • AFP

Stimulation of an anti-tumor immune response with "chromatin-damaging" therapy. (PubMed, Cancer Immunol Immunother) - "CBL0137 also elevated the number of CXCR3-expressing CTLs in the tumor and the level of interferon-γ-inducible protein 10 (IP-10) in serum, suggesting IP-10/CXCR3 controls CBL0137-elicited recruitment of effector CTLs to tumors. Our collective data underscores a previously unrecognized role for both innate and adaptive immunity in the anti-tumor activity of curaxins."

Journal • Oncology

Targeting histone chaperone FACT complex sensitizes medulloblastoma cells to chemo and radiation therapy (AACR 2018) - "Of importance, downregulation of APE1 levels or inhibition of FACT with CBL0137/curaxin sensitizes a panel of highly aggressive MB cell lines to cisplatin and alkylating drug temozolomide.Together, our study suggest that co-suppression of both BER and NER pathways via targeting FACT complex can greatly sensitize MB tumors to chemo and radiation therapy. A major implication of our studies is that combination of curaxin with low dose of cisplatin may have considerable therapeutic potential to improve efficacy and reduce cytotoxic side effects of cisplatin to MB patients."

Neuroendocrine Tumor

Study of IV CBL0137 in Previously Treated Hematological Subjects (clinicaltrials.gov) - P1; N=5; Terminated; Sponsor: Incuron; N=230 ➔ 5; Suspended ➔ Terminated; Business reasons

Clinical • Enrollment change • Trial termination • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Oncology

CBL0137 increases the targeting efficacy of Rovalpituzumab tesirine against tumour-initiating cells in small cell lung cancer. (PubMed, Br J Cancer) - "Therefore, we investigated the potential effect of combining Rova-T and CBL in SCLC to eradicate TICs more effectively. Our preclinical studies report a novel and highly translatable therapeutic strategy of dual targeting TICs using Rova-T in combination with CBL to potentially increase survival of SCLC patients."

Clinical • Journal • Lung Cancer • Movement Disorders • Oncology • Small Cell Lung Cancer • Solid Tumor

The small molecule drug CBL0137 increases the level of DNA damage and the efficacy of radiotherapy for glioblastoma. (PubMed, Cancer Lett) - "As GBM CSCs contribute to the inevitable recurrence in patients, targeting them is imperative. This work establishes a new treatment paradigm for GBM that sensitizes CSCs to irradiation and may ultimately reduce tumor recurrence."

Clinical • Journal • Glioblastoma • Oncology • Solid Tumor

Effective inhibition of MYC-amplified group 3 medulloblastoma by FACT-targeted curaxin drug CBL0137. (PubMed, Cell Death Dis) - "Moreover, it selectively disrupted transcription of MYC and NEUROD1, two critical oncogenic transcription factors of MYCamp-G3-MB, via depleting FACT complex from their promoter regions. In summary, our study demonstrates FACT-targeted CBL0137 works effectively on treating MYCamp-G3-MB, presenting another promising epigenetic-targeted therapeutic strategy against the most devastating form of MB."

Journal • Medulloblastoma • Oncology • Pediatrics • Solid Tumor

[VIRTUAL] Small molecule drug CBL0137 inhibits the FACT complex and sensitizes glioblastoma cancer stem cells to radiotherapy (SNO 2020) - "Radiotherapy remains a critical component of patient care for GBM, even though there exists a resistant subpopulation. Radio-sensitizing agents, including CBL0137, pose an exciting treatment paradigm to increase the efficacy of irradiation, especially by inclusively targeting CSCs."

Cancer stem cells • Glioblastoma • Oncology • Solid Tumor

A Translational Hepatic Artery Infusion (HAI) Model for Hepatocellular Carcinoma in Woodchucks. (PubMed, J Surg Res) - "HAI via GDA was a feasible and reproducible approach with low morbidity and mortality in woodchucks. The described techniques serve as a reliable platform for the identification and characterization of therapeutics for HCC."

Journal • Anorexia • Gastrointestinal Cancer • Hematological Disorders • Hemophilia • Hepatocellular Cancer • Hepatology • Oncology

CBL0137 administration suppresses human hepatocellular carcinoma cells proliferation and induces apoptosis associated with multiple cell death related proteins. (PubMed, Neoplasma) - "Moreover, HE staining and IHC staining for Ki-67 indicated that CBL0137 treatment could obviously induce cell apoptosis and suppress cell proliferation. CBL0137 treatment could effectively inhibit HCC cell proliferation and induce cell apoptosis associated with multiple factors expression."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor

Spt16 promotes lung cancer malignancy and is negatively regulated by miR-1227-5p. (PubMed, Cancer Sci) - "Furthermore, we found that CBL0137, the functional inhibitor of FACT, showed similar effects as loss of Spt16. Together, our data indicated that Spt16 is likely to be an essential regulator for lung cancer malignancy and is negatively regulated by miR-1227-5p."

Journal • Lung Cancer • Oncology • Solid Tumor