Trial reportJournal of hematology & oncology2014
A phase I study of AST1306, a novel irreversible EGFR and HER2 kinase inhibitor, in patients with advanced solid tumors.
Trial report in Journal of hematology & oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- A randomized, open-label, two-cycle, two-crossover phase I clinical trial comparing the bioequivalence and safety of afatinib and GiotrifJournal of cancer research and clinical oncology · 2023Trial
- Randomized Phase 2 Trial of Pharmacodynamic Separation of Pemetrexed and Intercalated Erlotinib Versus Pemetrexed Alone for Advanced Nonsquamous, Non-small-cell Lung Cancer.Clinical lung cancer · 2017Trial
- Exploring tyrosine kinase inhibitors for HER2-positive breast cancer: comprehensive review on a complete pharmacology-molecular mechanisms, safety profiles, and insights from preclinical and clinical studies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Advances in Small-molecule Dual Inhibitors Targeting EGFR and HER2 Receptors as Anti-cancer Agents.Current medicinal chemistry · 2025Review
- Mechanisms and therapeutic targets of ErbB family receptors in hepatocellular carcinoma: a narrative review.Translational cancer research · 2024Review
- New clinical trial design in precision medicine: discovery, development and direction.Signal transduction and targeted therapy · 2024Review
- The impact of nitric oxide on HER family post-translational modification and downstream signaling in cancer.Frontiers in physiology · 2024Review
- Recent advances in targeting the "undruggable" proteins: from drug discovery to clinical trials.Signal transduction and targeted therapy · 2023Review
- Prognostic biomarkers and molecular pathways mediating Helicobacter pylori-induced gastric cancer: a network-biology approach.Genomics & informatics · 2023Article
- Efficacy of Combined Use of Everolimus and Second-Generation Pan-EGRF Inhibitors inInternational journal of molecular sciences · 2022Article
- A Review of HER4 (ErbB4) Kinase, Its Impact on Cancer, and Its Inhibitors.Molecules (Basel, Switzerland) · 2021Review
- EGFR-TKIs resistance via EGFR-independent signaling pathways.Molecular cancer · 2018Review
- AKT can modulate theOncotarget · 2017Article
- Optofluidic device for the quantification of circulating tumor cells in breast cancer.Scientific reports · 2017Article
- Emerging therapeutic agents for lung cancer.Journal of hematology & oncology · 2016Review
- MiR-31 Regulates Rho-Associated Kinase-Myosin Light Chain (ROCK-MLC) Pathway and Inhibits Gastric Cancer Invasion: Roles of RhoA.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
- CD44 correlates with clinicopathological characteristics and is upregulated by EGFR in breast cancer.International journal of oncology · 2016Article
- Cytotoxicity of allitinib, an irreversible anti-EGFR agent, in a large panel of human cancer-derived cell lines: KRAS mutation status as a predictive biomarker.Cellular oncology (Dordrecht, Netherlands) · 2016Article
- Long lasting MDM2/Translocator protein modulator: a new strategy for irreversible apoptosis of human glioblastoma cells.Oncotarget · 2016Article
- Tumor suppressor microRNA-31 inhibits gastric carcinogenesis by targeting Smad4 and SGPP2.Cancer gene therapy · 2015Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAST1306 is an orally active irreversible small molecule inhibitor of EGFR (erbB1), HER2 (erbB2) and HER4 (erbB4) signaling. This is a phase I, open-label, dose-escalation study to evaluate the safety and tolerability, pharmacokinetics (PK), and preliminary anti-tumor effects of oral AST1306. In addition the effects of food on PK was tested.
methodsA modified Fibonacci 3 plus 3 dose-escalation design was employed to determine the dose-limiting toxicity (DLT) and recommended phase II dose (RP2D) in patients with advanced solid tumors. The following dose levels were investigated: once daily (QD) at two dose levels (400-and 800 mg), twice daily (BID) in five dose levels (600-, 800-, 1000-, 1200- and 1500 mg), and three times daily (TID) in three dose levels (800-, 1000- and 1200 mg). In the PK and extension study, at least eight patients per dose cohort in three dose levels (maximum tolerated dose [MTD], one or two doses level lower than the MTD) were enrolled to evaluate the PK profiles.
resultsSeventy-one patients were enrolled, with breast (n = 22) and lung cancers (n = 14) being the most common primary cancers. The most frequent drug-related adverse events were grade 1 to 3 diarrhea and rash, grade 1 to 2 fatigue. During dose escalation, the key DLT was grade 3 diarrhea observed in 5 patients at 1000 mg BID (n = 1), 1500 mg BID (n = 1), 800 mg TID (n = 1) and 1200 mg TID (n = 2). AST1306 was rapidly absorbed and had moderate to high clearance. PK concentration parameters increased with dose over the range evaluated, with no evidence of accumulation over time. Under fed conditions, the mean T(max) was prolonged, C(max) was increased, and AUC(0-∞) was raised. Of the 55 evaluable patients, 7 patients experienced partial responses, including 5 with breast cancer, 1 with lung cancer, and 1 with gastric cancer. The best response with stable disease for ≥ 6 months was achieved in 7 patients.
conclusionsBased on the DLT and PK profile, the RP2D was defined as 1000 mg TID with evidence of preliminary anti-tumor activity. Further studies are recommended.
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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.