Trial reportCancer chemotherapy and pharmacology2013
A phase 2 study of KX2-391, an oral inhibitor of Src kinase and tubulin polymerization, in men with bone-metastatic castration-resistant prostate cancer.
Trial report in Cancer chemotherapy and pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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.
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Who cites it
44 citing papers in PubMed, 75 citations in OpenAlex.
- Docetaxel and dasatinib or placebo in men with metastatic castration-resistant prostate cancer (READY): a randomised, double-blind phase 3 trial.The Lancet. Oncology · 2013Trial
- Non-receptor tyrosine kinase signaling pathways and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Integrative genomic profiling of iron homeostasis predicts clinical outcomes and identifies HAMP/hepcidin as a therapeutic target in colorectal cancer.Cell & bioscience · 2026Article
- Development and validation of a CAF-related signature for prognosis and therapy response in colorectal cancer: new insights on HSPB1.NPJ precision oncology · 2025Article
- Src/FN1 pathway activation drives tumor cell cluster formation and metastasis in lung cancer: A promising therapeutic target.Science advances · 2025Article
- PM534, an Optimized Target-Protein Interaction Strategy through the Colchicine Site of Tubulin.Journal of medicinal chemistry · 2024Article
- The emerging role of osteoclasts in the treatment of bone metastases: rationale and recent clinical evidence.Frontiers in oncology · 2024Review
- Synthesis and evaluation of tirbanibulin derivatives: a detailed exploration of the structure-activity relationship for anticancer activity.RSC advances · 2023Article
- Macrophages promote anti-androgen resistance in prostate cancer bone disease.The Journal of experimental medicine · 2023Article
- Pharmacological inhibition of the SKP2/p300 signaling axis restricts castration-resistant prostate cancer.Neoplasia (New York, N.Y.) · 2023Article
- FGF19-mediated ELF4 overexpression promotes colorectal cancer metastasis through transactivating FGFR4 and SRC.Theranostics · 2023Article
- A phase Ib dose escalation study of oral monotherapy with KX2-391 in elderly patients with acute myeloid leukemia.Investigational new drugs · 2022Article
- Advancing Treatment of Bone Metastases through Novel Translational Approaches Targeting the Bone Microenvironment.Cancers · 2022Review
- Targeting p130Cas- and microtubule-dependent MYC regulation sensitizes pancreatic cancer to ERK MAPK inhibition.Cell reports · 2021Article
- Tirbanibulin: First Approval.Drugs · 2021Review
- Tirbanibulin Attenuates Pulmonary Fibrosis by Modulating Src/STAT3 Signaling.Frontiers in pharmacology · 2021Article
- Insights on Cancer Cell Inhibition, Subcellular Activities, and Kinase Profile of Phenylacetamides Pending 1Frontiers in pharmacology · 2021Article
- STAT3 and p53: Dual Target for Cancer Therapy.Biomedicines · 2020Review
- Position of Circulating Tumor Cells in the Clinical Routine in Prostate Cancer and Breast Cancer Patients.Cancers · 2020Review
- Targeting STAT3 in Cancer Immunotherapy.Molecular cancer · 2020Review
Corrections and comments
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Authors and funding
13 authors at 10 institutions in 2 countries.
Funding
Abstract
purposeKX2-391 is an oral non-ATP-competitive inhibitor of Src kinase and tubulin polymerization. In phase 1 trials, prostate-specific antigen (PSA) declines were seen in patients with advanced prostate cancer. We conducted a single-arm phase 2 study evaluating KX2-391 in men with chemotherapy-naïve bone-metastatic castration-resistant prostate cancer (CRPC).
methodsWe treated 31 patients with oral KX2-391 (40 mg twice-daily) until disease progression or unacceptable toxicity. The primary endpoint was 24-week progression-free survival (PFS); a 50 % success rate was pre-defined as clinically significant. Secondary endpoints included PSA progression-free survival (PPFS) and PSA response rates. Exploratory outcomes included pharmacokinetic studies, circulating tumor cell (CTC) enumeration, and analysis of markers of bone resorption [urinary N-telopeptide (uNTx); C-telopeptide (CTx)] and formation [bone alkaline phosphatase (BAP); osteocalcin].
resultsThe trial closed early after accrual of 31 patients, due to a pre-specified futility rule. PFS at 24 weeks was 8 %, and median PFS was 18.6 weeks. The PSA response rate (≥ 30 % decline) was 10 %, and median PPFS was 5.0 weeks. Additionally, 18 % of men with unfavorable (≥ 5) CTCs at baseline converted to favorable (<5) CTCs with treatment. The proportion of men with declines in bone turnover markers was 32 % for uNTx, 21 % for CTx, 10 % for BAP, and 25 % for osteocalcin. In pharmacokinetic studies, median C max was 61 (range 16-129) ng/mL, and median AUC was 156 (35-348) ng h/mL. Common toxicities included hepatic derangements, myelosuppression, fatigue, nausea, and constipation.
conclusionKX2-391 dosed at 40 mg twice-daily lacks antitumor activity in men with CRPC, but has modest effects on bone turnover markers. Because a C max of ≥142 ng/mL is required for tubulin polymerization inhibition (defined from preclinical studies), higher once-daily dosing will be used in future trials.
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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.