ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
A Phase I Expansion Cohort Study Evaluating the Safety and Efficacy of the CHK1 Inhibitor LY2880070 with Low-dose Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02632448 (A Phase 1b/2a Three-Part Open-Label Multicenter Study to Evaluate the Safety and Efficacy of LY2880070 as Monotherapy and in Combination With Gemcitabine in Patients With Advanced or Metastatic Cancer), which is not on this map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1b/2a Three-Part Open-Label Multicenter Study to Evaluate the Safety and Efficacy of LY2880070 as Monotherapy and in Combination With Gemcitabine in Patients With Advanced or Metastatic Cancer
Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Organoids in translation: a bench-to-bedside framework for pancreatic cancer precision medicine.Journal of translational medicine · 2026Pooled it
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Rethinking the role of synergy calculations in the next century of drug combination discovery.Med (New York, N.Y.) · 2026Review
- Integrated computational-experimental pipeline for CHK1 inhibitor discovery: structure-based identification of novel chemotypes with anticancer activity.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- DNA damage response inhibitors in pancreatic cancer: progress and challenges.Frontiers in oncology · 2026Review
- Targeting DNA repair mechanisms in cancer therapy: the role of small molecule DNA repair inhibitors.NAR cancer · 2025Review
- Current progress in targeting mitotic kinases in PDAC.RSC medicinal chemistry · 2025Review
- Targeting the DNA damage response in cancer.MedComm · 2024Review
- Proapoptotic activity of JNK-sensitive BH3-only proteins underpins ovarian cancer response to replication checkpoint inhibitors.Molecular cancer · 2024Article
- The BET inhibitor sensitivity is associated with the expression level of CDC25B in pancreatic cancer models.Cancer drug resistance (Alhambra, Calif.) · 2024Article
- Telomere-related DNA damage response pathways in cancer therapy: prospective targets.Frontiers in pharmacology · 2024Review
Corrections and comments
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Authors and funding
28 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeCombining gemcitabine with CHK1 inhibition has shown promise in preclinical models of pancreatic ductal adenocarcinoma (PDAC). Here, we report the findings from a phase I expansion cohort study (NCT02632448) investigating low-dose gemcitabine combined with the CHK1 inhibitor LY2880070 in patients with previously treated advanced PDAC. PATIENTS AND
methodsPatients with metastatic PDAC were treated with gemcitabine intravenously at 100 mg/m2 on days 1, 8, and 15, and LY2880070 50 mg orally twice daily on days 2-6, 9-13, and 16-20 of each 21-day cycle. Pretreatment tumor biopsies were obtained from each patient for correlative studies and generation of organoid cultures for drug sensitivity testing and biomarker analyses.
resultsEleven patients with PDAC were enrolled in the expansion cohort between August 27, 2020 and July 30, 2021. Four patients (36%) experienced drug-related grade 3 adverse events. No objective radiologic responses were observed, and all patients discontinued the trial by 3.2 months. In contrast to the lack of efficacy observed in patients, organoid cultures derived from biopsies procured from two patients demonstrated strong sensitivity to the gemcitabine/LY2880070 combination and showed treatment-induced upregulation of replication stress and DNA damage biomarkers, including pKAP1, pRPA32, and γH2AX, as well as induction of replication fork instability.
conclusionsNo evidence of clinical activity was observed for combined low-dose gemcitabine and LY2880070 in this treatment-refractory PDAC cohort. However, the gemcitabine/LY2880070 combination showed in vitro efficacy, suggesting that drug sensitivity for this combination in organoid cultures may not predict clinical benefit in patients.
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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.