ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Safety, Antitumor Activity, and Biomarker Analysis in a Phase I Trial of the Once-daily Wee1 Inhibitor Adavosertib (AZD1775) in Patients with Advanced Solid Tumors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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The trial behind it
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Who cites it
46 citing papers in PubMed, 66 citations in OpenAlex.
- Phase II Study of Adavosertib in Patients With Tumors Containing BRCA1 and BRCA2 Mutations: Results From the NCI-MATCH ECOG-ACRIN Cancer Research Group (EAY131) Subprotocol Z1I.JCO precision oncology · 2026Trial
- A Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2-Altered Advanced Solid Tumor Malignancies (NCI 10170).Cancer research communications · 2024Trial
- Multicenter Phase II Trial of the WEE1 Inhibitor Adavosertib in Refractory Solid Tumors HarboringJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Trial
- CCNE1: A Cell Cycle Regulator That Influences Tumor Progression.Cancer medicine · 2026Review
- Article
- WEE1 kinase in cancer: Molecular mechanisms and inhibitor insights.EXCLI journal · 2026Review
- WEE1 inhibition delays resistance to CDK4/6 inhibitor and antiestrogen treatment in ER+ MCF7 cells.NPJ systems biology and applications · 2025Article
- Genome instability and crosstalk with the immune response.Genome medicine · 2025Review
- Article
- WEE1 inhibitors synergise with mRNA translation defects via activation of the kinase GCN2.Nature communications · 2025Article
- Targeting WEE1 to Overcome ARID1A Mutation-Driven Osimertinib Resistance in EGFR-Mutant Lung Cancer.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025Article
- The RING finger E3 ligase RNF25 protects DNA replication forks independently of its canonical roles in ubiquitin signaling.Nature communications · 2025Article
- Phase I Study of Adavosertib with Radiotherapy and Temozolomide in Newly Diagnosed Glioblastoma and Intratumoral Drug Levels in Recurrent Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- The RING Finger E3 Ligase RNF25 Protects DNA Replication Forks Independently of its Canonical Roles in Ubiquitin Signaling.bioRxiv : the preprint server for biology · 2025Article
- Cyclin E1/CDK2 activation defines a key vulnerability to WEE1 kinase inhibition in gynecological cancers.NPJ precision oncology · 2025Article
- High-Grade Endometrial Cancer: Molecular Subtypes, Current Challenges, and Treatment Options.Reproductive sciences (Thousand Oaks, Calif.) · 2024Review
- Copy number signatures and CCNE1 amplification reveal the involvement of replication stress in high-grade endometrial tumors oncogenesis.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Synergistic induction of mitotic pyroptosis and tumor remission by inhibiting proteasome and WEE family kinases.Signal transduction and targeted therapy · 2024Article
- Targeting WEE1 enhances the antitumor effect of KRAS-mutated non-small cell lung cancer harboring TP53 mutations.Cell reports. Medicine · 2024Article
- Current and Future Therapeutic Targets for Directed Molecular Therapies in Cholangiocarcinoma.Cancers · 2024Review
Corrections and comments
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Authors and funding
24 authors at 3 institutions in 1 country.
Funding
Abstract
purposeThe Wee1 kinase inhibitor adavosertib abrogates cell-cycle arrest, leading to cell death. Prior testing of twice-daily adavosertib in patients with advanced solid tumors determined the recommended phase II dose (RPh2D). Here, we report results for once-daily adavosertib. PATIENTS AND
methodsA 3 + 3 dose-escalation design was used, with adavosertib given once daily on days 1 to 5 and 8 to 12 in 21-day cycles. Molecular biomarkers of Wee1 activity, including tyrosine 15-phosphorylated Cdk1/2 (pY15-Cdk), were assessed in paired tumor biopsies. Whole-exome sequencing and RNA sequencing of remaining tumor tissue identified potential predictive biomarkers.
resultsAmong the 42 patients enrolled, the most common toxicities were gastrointestinal and hematologic; dose-limiting toxicities were grade 4 hematologic toxicity and grade 3 fatigue. The once-daily RPh2D was 300 mg. Six patients (14%) had confirmed partial responses: four ovarian, two endometrial. Adavosertib plasma exposures were similar to those from twice-daily dosing. On cycle 1 day 8 (pre-dose), tumor pY15-Cdk levels were higher than baseline in four of eight patients, suggesting target rebound during the day 5 to 8 dosing break. One patient who progressed rapidly had a tumor
conclusionsWe determined the once-daily adavosertib RPh2D and observed activity in patients with ovarian or endometrial carcinoma, including two with baseline
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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.