ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
A Phase Ib Study of the DNA-PK Inhibitor Peposertib Combined with Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03770689 (A Multicenter Study With an Open-label Phase Ib Part Followed by a Randomized, Placebo-controlled, Double-blind, Phase II Part to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics of the DNA-PK Inhibitor Peposertib), which is not on this map. Cited by 19 papers.
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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 Multicenter Study With an Open-label Phase Ib Part Followed by a Randomized, Placebo-controlled, Double-blind, Phase II Part to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics of the DNA-PK Inhibitor Peposertib (M3814) in Combination With Capecitabine and RT in Participants With Locally Advanced Rectal Cancer
Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- The DNA-PK inhibitor AZD7648 alone or combined with pegylated liposomal doxorubicin in patients with advanced cancer: results of a first-in-human Phase I/IIa study.British journal of cancer · 2025Trial
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- DNA-dependent protein kinase inhibition as a radiosensitizer in rectal cancer: toxicity must be evaluated in the context of organ preservation.Journal of gastrointestinal oncology · 2026Article
- Late toxicity after peposertib-enhanced chemoradiation in rectal cancer patients managed with organ preservation.Clinical and translational radiation oncology · 2026Article
- Review
- DNA-PKcs controls the cytotoxic T cell response to cancer and transplant allograft through regulating LAT-dependent signaling.Cell reports · 2026Article
- Orthogonally targeted tumor radiosensitization using cell penetrating peptide-ATM inhibitor conjugates to stimulate anti-tumor immune responses.bioRxiv : the preprint server for biology · 2026Article
- Combined carbon ion radiotherapy and immunotherapy: leveraging the immunological advantages of carbon ion.Frontiers in immunology · 2026Review
- POLQ and DNA-PK inhibition in muscle-invasive bladder cancer : Enhancing radiosensitivity with novel DNA damage response inhibitors to improve radiotherapy outcomes.Pathologie (Heidelberg, Germany) · 2026Article
- Next Generation DNA Damage Response Inhibitors: Harnessing Nanocarriers and Tumor Microenvironment for Precision Cancer Therapy.Oncology research · 2026Review
- Past present and future of radiosensitization in cervical cancer.Frontiers in oncology · 2026Review
- Targeting DNA repair mechanisms in cancer therapy: the role of small molecule DNA repair inhibitors.NAR cancer · 2025Review
- Targeting DNA Damage Repair Pathways Beyond PARP Inhibition.Targeted oncology · 2025Review
- DNA-PKcs-Driven YAP1 Phosphorylation and Nuclear Translocation: a Key Regulator of Ferroptosis in Hyperglycemia-Induced Cardiac Dysfunction in Type 1 Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- DNA-PK Inhibition Shows Differential Radiosensitization in Orthotopic GBM PDX Models Based on DDR Pathway Deficits.Molecular cancer therapeutics · 2025Article
- Emerging innovations in theranostics for pancreatic neuroendocrine tumors.NPJ precision oncology · 2025Review
- DNA-dependent protein kinase inhibitor as a sensitizer of radiotherapy in locally advanced rectal cancer.Journal of gastrointestinal oncology · 2024Article
- Impact of Optimized Ku-DNA Binding Inhibitors on the Cellular and In Vivo DNA Damage Response.Cancers · 2024Article
- Identification of 6-Anilino Imidazo[4,5-Journal of medicinal chemistry · 2024Article
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Authors and funding
13 authors at 9 institutions in 5 countries.
Funding
Abstract
purposePeposertib-an orally administered DNA-dependent protein kinase inhibitor-has shown potent radiosensitization in preclinical models. This dose-escalation study (NCT03770689) aimed to define the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of peposertib plus capecitabine-based chemoradiotherapy (CRT) and assessed its safety and efficacy in locally advanced rectal cancer. PATIENTS AND
methodsPatients were treated for 5 to 5.5 weeks with 50- to 250-mg peposertib once daily, capecitabine 825 mg/m2 twice daily, and radiotherapy (RT), 5 days per week. Following clinical restaging (8 weeks after CRT completion), patients with clinical complete response (cCR) could opt for surveillance. Total mesorectal excision was recommended upon incomplete response (IR).
resultsNineteen patients were treated with peposertib at doses of 50 mg (n = 1), 100 mg, 150 mg, and 250 mg (n = 6 each). Dose-limiting toxicities occurred in one out of five (100 mg), one out of six (150 mg), and three out of six (250 mg) evaluable patients. Peposertib ≤150 mg once daily was tolerable in combination with CRT. After 8 weeks of treatment with peposertib and CRT, the cCR was 15.8% (n = 3). Among the three patients with cCR, two underwent surgery and had residual tumors. Among the 16 patients with IR, seven underwent surgery and had residual tumors; five of the remaining nine patients opted for consolidative chemotherapy. The combined cCR/pathologic complete response (pCR) rate was 5.3% (n = 1, 100 mg cohort).
conclusionsPeposertib did not improve complete response rates at tolerable dose levels. The study was closed without declaring the MTD/RP2D.
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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.