Trial reportCancer2023
Pediatric phase 2 trial of a WEE1 inhibitor, adavosertib (AZD1775), and irinotecan for relapsed neuroblastoma, medulloblastoma, and rhabdomyosarcoma.
Trial report in Cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Relapsed rhabdomyosarcoma: treatment recommendations from the European pediatric soft tissue sarcoma study group (EpSSG).British journal of cancer · 2025Guideline
- Paediatric therapeutic development workshop on medulloblastoma.British journal of cancer · 2026Review
- Article
- Article
- WEE1 kinase in cancer: Molecular mechanisms and inhibitor insights.EXCLI journal · 2026Review
- ATRX large deletions and truncating mutations are associated with primary induction chemotherapy resistance in high-risk neuroblastoma: a multicenter propensity-weighted cohort study.Frontiers in oncology · 2026Article
- Medulloblastoma: Current Standard of Care and Future Treatment Opportunities.Paediatric drugs · 2026Review
- Atypical R-loops in cancer: decoding molecular chaos for therapeutic gain.Journal of translational medicine · 2025Review
- Transcriptionally distinct malignant neuroblastoma populations show selective response to adavosertib treatment.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Mechanisms of telomere maintenance and associated therapeutic vulnerabilities in malignant gliomas.Neuro-oncology · 2024Review
- What are the Optimal Systemic Treatment Options for Rhabdomyosarcoma?Current treatment options in oncology · 2024Review
- Review
- Key Proteins of Replication Stress Response and Cell Cycle Control as Cancer Therapy Targets.International journal of molecular sciences · 2024Review
- Targeting WEE1 kinase as a p53-independent therapeutic strategy in high-risk and relapsed acute lymphoblastic leukemia.Cancer cell international · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundInhibition of the WEE1 kinase by adavosertib (AZD1775) potentiates replicative stress from genomic instability or chemotherapy. This study reports the pediatric solid tumor phase 2 results of the ADVL1312 trial combining irinotecan and adavosertib.
methodsPediatric patients with recurrent neuroblastoma (part B), medulloblastoma/central nervous system embryonal tumors (part C), or rhabdomyosarcoma (part D) were treated with irinotecan and adavosertib orally for 5 days every 21 days. The combination was considered effective if there were at least three of 20 responses in parts B and D or six of 19 responses in part C. Tumor tissue was analyzed for alternative lengthening of telomeres and ATRX. Patient's prior tumor genomic analyses were provided.
resultsThe 20 patients with neuroblastoma (part B) had a median of three prior regimens and 95% had a history of prior irinotecan. There were three objective responses (9, 11, and 18 cycles) meeting the protocol defined efficacy end point. Two of the three patients with objective responses had tumors with alternative lengthening of telomeres. One patient with pineoblastoma had a partial response (11 cycles), but parts C and D did not meet the protocol defined efficacy end point. The combination was well tolerated and there were no dose limiting toxicities at cycle 1 or beyond in any parts of ADVL1312 at the recommended phase 2 dose.
conclusionThis is first phase 2 clinical trial of adavosertib in pediatrics and the first with irinotecan. The combination may be of sufficient activity to consider further study of adavosertib in neuroblastoma.
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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.