ArticlePediatric blood & cancer2021
A phase 1 study of prexasertib (LY2606368), a CHK1/2 inhibitor, in pediatric patients with recurrent or refractory solid tumors, including CNS tumors: A report from the Children's Oncology Group Pediatric Early Phase Clinical Trials Network (ADVL1515).
Article in Pediatric blood & cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
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- Therapeutic Targeting of DNA Damage Response Pathways inBrain tumor research and treatment · 2025Review
- Co-inhibition of Notch1 and ChK1 triggers genomic instability and melanoma cell death increasing the lifespan of mice bearing melanoma brain metastasis.Journal of experimental & clinical cancer research : CR · 2025Article
- Antitumor Activity of Radiation Therapy Combined with Checkpoint Kinase Inhibition in SHH/International journal of molecular sciences · 2025Article
- ACR-368, a CHK1/2 Kinase Inhibitor, in Patients With Relapsed or Refractory Desmoplastic Small Round Cell Tumor: Phase I/II Trial Results.JCO oncology advances · 2025Article
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- CHK1 inhibitor induced PARylation by targeting PARG causes excessive replication and metabolic stress and overcomes chemoresistance in ovarian cancer.Cell death discovery · 2024Article
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- Key Proteins of Replication Stress Response and Cell Cycle Control as Cancer Therapy Targets.International journal of molecular sciences · 2024Review
- Radiofrequency ablation for pediatric recurrent hepatocellular carcinoma: a single-center experience.BMC medical imaging · 2023Article
- Maintaining Genome Integrity: Protein Kinases and Phosphatases Orchestrate the Balancing Act of DNA Double-Strand Breaks Repair in Cancer.International journal of molecular sciences · 2023Review
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- Targeting Replication Stress Response Pathways to Enhance Genotoxic Chemo- and Radiotherapy.Molecules (Basel, Switzerland) · 2022Review
- FGFR2 loss sensitizes MYCN-amplified neuroblastoma CHP134 cells to CHK1 inhibitor-induced apoptosis.Cancer science · 2022Article
- Review
- Identifying novel SMYD3 interactors on the trail of cancer hallmarks.Computational and structural biotechnology journal · 2022Article
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- A combination of PARP and CHK1 inhibitors efficiently antagonizes MYCN-driven tumors.Oncogene · 2021Article
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Authors and funding
8 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundPrexasertib (LY2606368) is a novel, second-generation, selective dual inhibitor of checkpoint kinase proteins 1 (CHK1) and 2 (CHK2). We conducted a phase 1 trial of prexasertib to estimate the maximum-tolerated dose (MTD) and/or recommended phase 2 dose (RP2D), to define and describe the toxicities, and to characterize the pharmacokinetics (PK) of prexasertib in pediatric patients with recurrent or refractory solid and central nervous system (CNS) tumors.
methodsPrexasertib was administered intravenously (i.v.) on days 1 and 15 of a 28-day cycle. Four dose levels, 80, 100, 125, and 150 mg/m
resultsThirty patients were enrolled; 25 were evaluable. The median age was 9.5 years (range: 2-20) and 21 (70%) were male. Twelve patients (40%) had solid tumors and 18 patients (60%) had CNS tumors. There were no cycle 1 or later dose-limiting toxicities. Common cycle 1, drug-related grade 3/4 toxicities (> 10% of patients) included neutropenia (100%), leukopenia (68%), thrombocytopenia (24%), lymphopenia (24%), and anemia (12%). There were no objective responses; best overall response was stable disease in three patients for five cycles (hepatocellular carcinoma), three cycles (ependymoma), and five cycles (undifferentiated sarcoma). The PK appeared dose proportional across the 80-150 mg/m
conclusionsAlthough the MTD of prexasertib was not defined by this study, 150 mg/m
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.