ArticleBritish journal of cancer2024
Phase 1b study of enzalutamide plus CC-115, a dual mTORC1/2 and DNA-PK inhibitor, in men with metastatic castration-resistant prostate cancer (mCRPC).
Article in British journal of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02833883 (A Phase 1b Study of Enzalutamide Plus CC-115 in Men With Castration-Resistant Prostate Cancer), which is not on this map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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 Study of Enzalutamide Plus CC-115 in Men With Castration-Resistant Prostate Cancer (CRPC)
Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Targeting DNA-PK: medicinal chemistry insights into small-molecule inhibitor discovery and optimisation.RSC medicinal chemistry · 2026Review
- Novel therapeutic strategies for metastatic castration‑resistant prostate cancer: Beyond androgen receptor pathway inhibition (Review).International journal of oncology · 2026Review
- Intermittent Fasting and Androgen Receptor Signaling in Prostate Cancer: Metabolic Crosstalk and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Identification of CAND1 as a DNA-dependent protein kinase-regulated coactivator of androgen receptor and the ARv7 splice variant.PloS one · 2026Article
- Medicinal chemistry breakthroughs on ATM, ATR, and DNA-PK inhibitors as prospective cancer therapeutics.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Design, synthesis, and structure-activity relationship studies of 4-substituted phenylpyrazolidinone derivatives as potent Ku70/80 targeted DNA-PK inhibitors.RSC medicinal chemistry · 2025Article
- Novel hormone therapies for advanced prostate cancer: Understanding and countering drug resistance.Journal of pharmaceutical analysis · 2025Review
- Unlocking the Therapeutic Potential of DNA-PKcs in Cancer: Comprehensive Insights into Mechanisms and Clinical Applications.Cancers · 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
- Targeted and immunotherapeutic strategies for castration-resistant prostate cancer: emerging strategies, challenges, and future directions.Frontiers in immunology · 2025Review
- Impact of Optimized Ku-DNA Binding Inhibitors on the Cellular and In Vivo DNA Damage Response.Cancers · 2024Article
- Enzalutamide inhibits PEX10 function and sensitizes prostate cancer cells to ROS activators.Cell death & disease · 2024Article
- Advancing cancer therapy: new frontiers in targeting DNA damage response.Frontiers in pharmacology · 2024Review
- Review
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 5 countries.
Funding
Abstract
backgroundCC-115, a dual mTORC1/2 and DNA-PK inhibitor, has promising antitumour activity when combined with androgen receptor (AR) inhibition in pre-clinical models.
methodsPhase 1b multicentre trial evaluating enzalutamide with escalating doses of CC-115 in AR inhibitor-naive mCRPC patients (n = 41). Primary endpoints were safety and RP2D. Secondary endpoints included PSA response, time-to-PSA progression, and radiographic progression.
resultsCommon adverse effects included rash (31.7% Grades 1-2 (Gr); 31.7% Gr 3), pruritis (43.9% Gr 1-2), diarrhoea (37% Gr 1-2), and hypertension (17% Gr 1-2; 9.8% Gr 3). CC-115 RP2D was 5 mg twice a day. In 40 evaluable patients, 80% achieved ≥50% reduction in PSA (PSA50), and 58% achieved ≥90% reduction in PSA (PSA90) by 12 weeks. Median time-to-PSA progression was 14.7 months and median rPFS was 22.1 months. Stratification by PI3K alterations demonstrated a non-statistically significant trend towards improved PSA50 response (PSA50 of 94% vs. 67%, p = 0.08). Exploratory pre-clinical analysis suggested CC-115 inhibited mTOR pathway strongly, but may be insufficient to inhibit DNA-PK at RP2D.
conclusionsThe combination of enzalutamide and CC-115 was well tolerated. A non-statistically significant trend towards improved PSA response was observed in patients harbouring PI3K pathway alterations, suggesting potential predictive biomarkers of response to a PI3K/AKT/mTOR pathway inhibitor. CLINICAL
trial registrationClinicalTrials.gov identifier: NCT02833883.
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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.