{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT05081180","title":"Study of Avelumab in Combination With Lenvatinib for Children With Primary CNS Tumors","sponsor":"EMD Serono Research & Development Institute, Inc.","phases":["PHASE1"],"status":"TERMINATED","indication":null,"disease":"central nervous system cancer"},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"no","detail":"None of CD274, FLT1, FLT4, KDR has somatic-mutation evidence in central nervous system cancer","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: CD274 in central nervous system cancer","url":"https://platform.opentargets.org/evidence/ENSG00000120217/MONDO_0002714","date":"2026-11-11T18:29:50.731Z"},"context":[]},{"id":"human_genetic","label":"Human genetic evidence","value":"no","detail":"No germline or somatic evidence for CD274, FLT1, FLT4, KDR in central nervous system cancer","rule":"Any germline or somatic human genetic evidence for the target in this cancer, counted apart from animal-model and literature evidence","source":{"label":"Open Targets: CD274 in central nervous system cancer","url":"https://platform.opentargets.org/evidence/ENSG00000120217/MONDO_0002714","date":"2026-11-11T18:29:50.731Z"},"context":[]},{"id":"pediatric_target","label":"Pediatric target","value":"yes","detail":"CD274 on the FDA list","rule":"Target is on FDA's Pediatric Molecular Target List (relevant targets); membership alone neither requires nor waives a study","source":{"label":"FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01))","url":"https://www.fda.gov/media/191157/download?attachment","date":"2026-11-11T07:05:03Z"},"context":[]},{"id":"haematologic","label":"Haematologic cancer","value":"no","detail":"Solid tumour","rule":"From the indication, or the registry conditions when no indication matches","source":{"label":"ClinicalTrials.gov NCT05081180","url":"https://clinicaltrials.gov/study/NCT05081180","date":"2026-11-11T18:29:50.731Z"},"context":[{"figure":"Likelihood of approval from phase 1: 7.5% haematologic vs 4.6% solid","dataset":"BIO / Informa / QLS 2021","years":"2011–2020","caveat":"Population-level, not a prediction."}]}],"facts":[{"label":"CD274 (via Avelumab)","text":"Evidence types in central nervous system cancer: literature, clinical; literature listed separately from human genetics. Datasources: europepmc, clinical_precedence.","source":{"label":"Open Targets: CD274 in central nervous system cancer","url":"https://platform.opentargets.org/evidence/ENSG00000120217/MONDO_0002714","date":"2026-11-11T18:29:50.731Z"}},{"label":"FLT1 (via Lenvatinib)","text":"Evidence types in central nervous system cancer: literature, clinical; literature listed separately from human genetics. Datasources: europepmc, clinical_precedence.","source":{"label":"Open Targets: FLT1 in central nervous system cancer","url":"https://platform.opentargets.org/evidence/ENSG00000102755/MONDO_0002714","date":"2026-11-11T18:29:50.731Z"}},{"label":"FLT4 (via Lenvatinib)","text":"Evidence types in central nervous system cancer: literature, clinical; literature listed separately from human genetics. Datasources: europepmc, clinical_precedence.","source":{"label":"Open Targets: FLT4 in central nervous system cancer","url":"https://platform.opentargets.org/evidence/ENSG00000037280/MONDO_0002714","date":"2026-11-11T18:29:50.731Z"}},{"label":"KDR (via Lenvatinib)","text":"Evidence types in central nervous system cancer: literature, clinical; literature listed separately from human genetics. Datasources: europepmc, clinical_precedence.","source":{"label":"Open Targets: KDR in central nervous system cancer","url":"https://platform.opentargets.org/evidence/ENSG00000128052/MONDO_0002714","date":"2026-11-11T18:29:50.731Z"}}],"pending":[{"what":"Normal-tissue expression in vital organs","source":"Human Protein Atlas (ticket 36)"},{"what":"Pan-essential in cell lines","source":"DepMap (ticket 36)"},{"what":"Approved drug on this target","source":"Drugs@FDA (ticket 30)"}]},{"n":2,"question":"Can the result be trusted?","flags":[{"id":"randomised","label":"Randomised","value":"no","detail":"Single group","rule":"Registry allocation field","source":{"label":"ClinicalTrials.gov NCT05081180","url":"https://clinicaltrials.gov/study/NCT05081180","date":"2026-11-11T18:29:50.731Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"yes","detail":"17 enrolled; each patient moves a rate by 100 ÷ 17 = 5.9 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT05081180","url":"https://clinicaltrials.gov/study/NCT05081180","date":"2026-11-11T18:29:50.731Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"no","detail":"Dose Escalation Part 1: Number of Participants with Common Terminology Criteria for Adverse Events (CTCAE) Grade Grea…; Dose Escalation Part 1: Number of Participants With Dose Limiting Toxicities (DLTs); Dose Expansion Part 2: Progression-free Survival (PFS) According to Response Assessment in Neuro-Oncology (RANO) Crit…","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT05081180","url":"https://clinicaltrials.gov/study/NCT05081180","date":"2026-11-11T18:29:50.731Z"},"context":[{"figure":"Non-OS primary endpoint: odds ratio 2.79 for a positive phase 3","dataset":"Otsuka 2021, 400 phase 3 oncology trials","years":"to 2020","caveat":"Shown with the next figure: a surrogate is easier to hit, and often a weak guide to survival."},{"figure":"52% of surrogate-to-OS correlations are low","dataset":"Prasad 2015","years":"published to 2014","caveat":"Shown with the figure above."}]},{"id":"results_overdue","label":"Results overdue","value":"no","detail":"Primary completion 2026-02-11, 8 months ago; within 12 months","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT05081180","url":"https://clinicaltrials.gov/study/NCT05081180","date":"2026-11-11T18:29:50.731Z"},"context":[]}],"facts":[],"pending":[{"what":"Treated and evaluable counts, assessor, confirmed response, follow-up and data cutoff","source":"Readout extraction (ticket 32)"},{"what":"Primary endpoint changed between registry versions","source":"Registry versions in the store (ticket 32)"}]},{"n":3,"question":"What must it beat?","flags":[],"facts":[],"pending":[{"what":"Control-arm result and approved therapies for the same segment, with label links","source":"Drugs@FDA, FDA labels and readouts (tickets 30, 32)"}]},{"n":4,"question":"Too crowded, or too late?","flags":[],"facts":[{"label":"Stopped on this target","text":"415 terminated, withdrawn or suspended trials of drugs against CD274; 1 of the 200 most recent give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"CD274: what already stopped","url":"/target/ENSG00000120217#stopped","date":"2026-11-11T18:29:50.745Z"}}],"pending":[{"what":"Programs on the target by phase and months behind the leader","source":"Programs and Drugs@FDA (ticket 33)"}]},{"n":5,"question":"Can it be approved, and stay approved?","flags":[{"id":"single_country","label":"Single-country","value":"no","detail":"9 sites in 4 countries; 0 in the United States (0%)","rule":"All listed sites are in one country; the share of US sites is shown","source":{"label":"ClinicalTrials.gov NCT05081180","url":"https://clinicaltrials.gov/study/NCT05081180?tab=locations","date":"2026-11-11T18:29:50.731Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMEA-001849-PIP02-15-M05 (avelumab, Treatment of all conditions included in the category of malignant neoplasms (except central nervous system tumours, haematopoietic and lymphoid tissue neoplasms);Treatment of malignant neoplasms of lymphoid tissue;Treatment of malignant neoplasms of the central nervous system): PM: decision on the application for modification of an agreed PIP, 22 Aug 2024; EMEA-001119-PIP02-12-M08 (lenvatinib, Treatment of follicular thyroid cancer;Treatment of osteosarcoma;Treatment of papillary thyroid cancer): PM: decision on the application for modification of an agreed PIP, 10 Aug 2022; compliance positive 26 May 2023; EMEA-001119-PIP03-19-M03 (lenvatinib, Treatment of all conditions included in the category of malignant neoplasms except haematopoietic and lymphoid tissue neoplasms, papillary thyroid cancer, follicular thyroid cancer and osteosarcoma): PM: decision on the application for modification of an agreed PIP, 30 Dec 2022; compliance positive 13 Oct 2023","rule":"An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name","source":{"label":"EMA data download (dated snapshot)","url":"https://www.ema.europa.eu/en/documents/report/medicines-output-paediatric_investigation_plans-output-json-report_en.json","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"eu_orphan","label":"EU orphan designation","value":"yes","detail":"EU/3/15/1590 withdrawn 14 Dec 2015: Treatment of Merkel cell carcinoma; EU/3/16/1798 withdrawn 12 Dec 2016: Treatment of gastric cancer; EU/3/15/1460 withdrawn 19 Mar 2015: Treatment of hepatocellular carcinoma; EU/3/13/1121 withdrawn 26 Apr 2013: Treatment of papillary thyroid cancer; +1 more","rule":"An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status","source":{"label":"EMA data download (dated snapshot)","url":"https://www.ema.europa.eu/en/documents/report/medicines-output-orphan_designations-json-report_en.json","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"eu_authorised","label":"Authorised in the EU","value":"yes","detail":"Bavencio: authorised since 18 Sept 2017; Kisplyx: authorised since 25 Aug 2016; Lenvima: authorised since 28 May 2015","rule":"An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file","source":{"label":"EMA data download (dated snapshot)","url":"https://www.ema.europa.eu/en/documents/report/medicines-output-medicines_json-report_en.json","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"fda_orphan","label":"FDA orphan designation","value":"not published","detail":"FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the link","rule":"Would be: an FDA orphan designation names the drug","source":{"label":"FDA orphan designations search","url":"https://www.accessdata.fda.gov/scripts/opdlisting/oopd/","date":""},"context":[]},{"id":"fda_ped_approval","label":"FDA pediatric oncology approval","value":"yes","detail":"Avelumab [Bavencio], 23 Mar 2017: Treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC)","rule":"FDA's Pediatric Oncology Drug Approvals table names the drug","source":{"label":"FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03)","url":"https://www.fda.gov/about-fda/oncology-center-excellence/pediatric-oncology-drug-approvals","date":"2026-11-11T18:29:50.760Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"23 interventional studies of Avelumab, Lenvatinib include patients under 18; 7 are recruiting, not yet recruiting or active","rule":"The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age","source":{"label":"ClinicalTrials.gov search","url":"https://clinicaltrials.gov/search?intr=%22Avelumab%22+OR+%22Lenvatinib%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-11T18:29:50.769Z"},"context":[]}],"facts":[{"label":"Caveat","text":"Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where the sites are is a fact about the record, not a judgement of its quality."},{"label":"Rare pediatric disease voucher","text":"FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news.","source":{"label":"FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs","url":"https://www.fda.gov/industry/medical-products-rare-diseases-and-conditions/rare-pediatric-disease-designation-and-priority-review-voucher-programs","date":"2026-11-11"}}],"pending":[{"what":"Precedent approvals for target, modality and endpoint; accelerated-approval status","source":"Drugs@FDA and FDA accelerated-approval tables (ticket 30)"}]},{"n":6,"question":"Can the sponsor finish?","flags":[],"facts":[{"label":"Sponsor","text":"EMD Serono Research & Development Institute, Inc. (industry)","source":{"label":"ClinicalTrials.gov NCT05081180","url":"https://clinicaltrials.gov/study/NCT05081180","date":"2026-11-11T18:29:50.731Z"}},{"label":"study director","text":"Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany","source":{"label":"Person page","url":"/person/Medical%20Responsible","date":"2026-11-11T18:29:50.731Z"}}],"pending":[{"what":"Filed cash, quarterly spend and the runway arithmetic","source":"SEC XBRL company facts (ticket 37)"},{"what":"Sponsor's completed vs stopped oncology trials and results-reporting record","source":"Registry, by company (ticket 37)"}]}],"limits":"Public records cannot show: sales forecasts; a probability of success for this asset; full deal terms and net prices; FDA designations and action dates before approval (shown only as company-reported); clinical holds unless the company disclosed them; manufacturing; patents on unapproved drugs; whether preclinical findings have been replicated.","sources":[{"label":"ClinicalTrials.gov NCT05081180","url":"https://clinicaltrials.gov/study/NCT05081180","date":"2026-11-11T18:29:50.731Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T18:29:50.731Z"},{"label":"FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01))","url":"https://www.fda.gov/media/191157/download?attachment","date":"2026-11-11T07:05:03Z"}]},"source":"ClinicalTrials.gov + Open Targets","fetchedAt":"2026-11-11T18:29:50.728Z"}