CBL0137

Overview

CBL0137 (Curaxin 137) is a first‑in‑class small‑molecule curaxin being developed as an anticancer agent that targets the FAcilitates Chromatin Transcription (FACT) complex. It has been evaluated in adult phase I studies (intravenous and oral), explored in a regional intra‑arterial phase I study for extremity tumors, and is in an ongoing pediatric phase 1/2 trial for relapsed/refractory solid and CNS tumors and lymphoma. As of October 7, 2025, no randomized trials or registrational studies have reported results. (science.org)

Mechanism of action

• Target: FACT, a histone chaperone composed of SSRP1 and SPT16 that supports transcriptional elongation, replication, and DNA repair and is overexpressed in many tumors. (science.org)
• MOA: CBL0137 is a non‑genotoxic DNA intercalator that “traps” FACT on chromatin, leading to inhibition of FACT‑dependent transcription (including NF‑κB), activation/phosphorylation of p53 (via CK2), suppression of HSF1/MYC/HIF1α programs, and induction of an interferon response. (science.org)
• Tumor biology: FACT is enriched in glioblastoma and glioblastoma stem cells; CBL0137 crosses the blood–brain barrier and shows activity in preclinical GBM models, including temozolomide‑resistant disease. (academic.oup.com)
• Additional preclinical signals include activity in mesothelioma models and potential to enhance immunotherapy responses. (jeccr.biomedcentral.com)

Efficacy (clinical)

• Adults, IV phase I (NCT01905228): In 83 patients with advanced solid tumors treated on days 1, 8, 15 of 28‑day cycles across 10–700 mg/m², the best responses were disease stabilization; examples included durable stable disease (up to 24 months) and minor tumor regressions (<25%) in select patients (liver, prostate, uterine cancers). No confirmed RECIST objective responses were reported in the abstract. (ascopubs.org)
• Adults, oral phase Ib: First‑in‑human dose‑escalation (14 days on, 14 off per 28‑day cycle) established dosing parameters; the abstract reported safety/PK findings but did not report confirmed objective responses. (ascopubs.org)
• Intra‑arterial regional therapy phase I (extremity melanoma/sarcoma): Treatment was well tolerated with minimal toxicity; pharmacokinetics showed high tumor uptake and lower systemic exposure versus IV; one patient achieved prolonged disease stability. This exploratory study supports feasibility of regional delivery. (pubmed.ncbi.nlm.nih.gov)
• Pediatrics (NCT04870944): Ongoing COG phase 1/2 in children and young adults with relapsed/refractory solid tumors, including CNS tumors and lymphoma; no results posted as of September 2025. (clinicaltrials.ucsf.edu)

Overall, early‑phase clinical data to date demonstrate disease stabilization in a subset of patients without clear evidence of objective responses in unselected populations; later‑phase efficacy remains unestablished.

Safety

• IV phase I: Dose‑limiting toxicities were primarily myelosuppression (thrombocytopenia, neutropenia) and anemia at higher dose levels; photosensitivity and gastrointestinal adverse events (nausea/vomiting) were generally manageable with prophylaxis. Peripheral venous thrombosis led to the use of central venous access in glioblastoma patients. The MTD/RP2D was estimated at 540 mg/m² IV. Reported half‑life was approximately 25 hours with extensive tissue distribution. (ascopubs.org)
• Oral phase Ib: Abstract reported dose‑escalation, safety, and PK characterization; detailed toxicity rates were not provided in the abstract. (ascopubs.org)
• Intra‑arterial phase I: “Minimal to no toxicity” across treated patients; markedly decreased systemic exposure versus matched IV dosing. (pubmed.ncbi.nlm.nih.gov)

Further reading

• Mechanism and preclinical foundation:
• Curaxins: Anticancer compounds that simultaneously suppress NF‑κB and activate p53 by targeting FACT (Science Translational Medicine, 2011). (science.org)
• CBL0137 efficacy in orthotopic GBM, including TMZ‑resistant models (Neuro‑Oncology, 2017). (academic.oup.com)
• FACT targeting preferentially eliminates GBM stem cells (Cancer Research, 2016). (aacrjournals.org)

• FACT targeting in mesothelioma and immunotherapy enhancement (JECCR, 2023). (jeccr.biomedcentral.com)

• Clinical studies:

• IV phase I results (ASCO 2020 abstract). (ascopubs.org)
• Oral phase Ib results (ASCO 2020 abstract). (ascopubs.org)
• Intra‑arterial phase I in extremity melanoma/sarcoma (2025, PubMed). (pubmed.ncbi.nlm.nih.gov)
• Ongoing pediatric phase 1/2 (NCT04870944; trial pages at Dana‑Farber/UCSF). (dana-farber.org)

Notes: The available adult phase I abstracts provide limited granularity on response rates; the IV study reported best responses of stable disease with occasional minor regressions but no confirmed objective responses, and established an IV RP2D of 540 mg/m². Pediatric efficacy and safety results have not yet been reported publicly. (ascopubs.org)

Last updated: Oct 2025