{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT03646461","title":"Trial of Ibrutinib Combined With Nivolumab or Cetuximab to Treat Recurrent/Metastatic HNSCC","sponsor":"University of California, San Diego","phases":["PHASE2"],"status":"TERMINATED","indication":null,"disease":"head and neck cancer"},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"no","detail":"None of BTK, EGFR, PDCD1 has somatic-mutation evidence in head and neck cancer","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: BTK in head and neck cancer","url":"https://platform.opentargets.org/evidence/ENSG00000010671/MONDO_0005627","date":"2026-11-11T17:04:05.799Z"},"context":[]},{"id":"human_genetic","label":"Human genetic evidence","value":"no","detail":"No germline or somatic evidence for BTK, EGFR, PDCD1 in head and neck 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: BTK in head and neck cancer","url":"https://platform.opentargets.org/evidence/ENSG00000010671/MONDO_0005627","date":"2026-11-11T17:04:05.799Z"},"context":[]},{"id":"pediatric_target","label":"Pediatric target","value":"yes","detail":"EGFR, PDCD1 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 NCT03646461","url":"https://clinicaltrials.gov/study/NCT03646461","date":"2026-11-11T17:04:05.799Z"},"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":"BTK (via Ibrutinib)","text":"Evidence types in head and neck cancer: literature; literature listed separately from human genetics. Datasources: europepmc.","source":{"label":"Open Targets: BTK in head and neck cancer","url":"https://platform.opentargets.org/evidence/ENSG00000010671/MONDO_0005627","date":"2026-11-11T17:04:05.799Z"}},{"label":"EGFR (via Cetuximab)","text":"Evidence types in head and neck cancer: literature, affected_pathway, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, cancer_biomarkers, europepmc.","source":{"label":"Open Targets: EGFR in head and neck cancer","url":"https://platform.opentargets.org/evidence/ENSG00000146648/MONDO_0005627","date":"2026-11-11T17:04:05.799Z"}},{"label":"PDCD1 (via Nivolumab)","text":"Evidence types in head and neck cancer: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc.","source":{"label":"Open Targets: PDCD1 in head and neck cancer","url":"https://platform.opentargets.org/evidence/ENSG00000188389/MONDO_0005627","date":"2026-11-11T17:04:05.799Z"}}],"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":"yes","detail":"Randomised allocation","rule":"Registry allocation field","source":{"label":"ClinicalTrials.gov NCT03646461","url":"https://clinicaltrials.gov/study/NCT03646461","date":"2026-11-11T17:04:05.799Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"yes","detail":"5 enrolled; each patient moves a rate by 100 ÷ 5 = 20.0 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT03646461","url":"https://clinicaltrials.gov/study/NCT03646461","date":"2026-11-11T17:04:05.799Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"no","detail":"Clinical Efficacy of Combined Therapies Using RECIST v1.1","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT03646461","url":"https://clinicaltrials.gov/study/NCT03646461","date":"2026-11-11T17:04:05.799Z"},"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":"Results posted 2026-05-22","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT03646461","url":"https://clinicaltrials.gov/study/NCT03646461?tab=results","date":"2026-11-11T17:04:05.799Z"},"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":"102 terminated, withdrawn or suspended trials of drugs against BTK; 6 give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"BTK: what already stopped","url":"/target/ENSG00000010671#stopped","date":"2026-11-11T17:04:05.809Z"}}],"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":"yes","detail":"The only site is in United States","rule":"All listed sites are in one country; the share of US sites is shown","source":{"label":"ClinicalTrials.gov NCT03646461","url":"https://clinicaltrials.gov/study/NCT03646461?tab=locations","date":"2026-11-11T17:04:05.799Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMEA-002727-PIP03-23 (nivolumab;relatlimab, Treatment of melanoma): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 6 May 2024; EMA/PE/0000232936 (atigotatug;nivolumab, Treatment of small cell lung cancer): W: decision granting a waiver in all age groups for all conditions or indications, 21 Mar 2025; EMEA-001407-PIP02-15-M07 (nivolumab, 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, 6 May 2024; EMEA-002727-PIP02-23 (relatlimab;nivolumab, Treatment of all conditions included in the category of malignant neoplasms (except central nervous system tumours, hematopoietic and lymphoid tissue neoplasms and melanoma)): W: decision granting a waiver in all age groups for all conditions or indications, 1 Dec 2023; +9 more","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/3/26/3215 positive 25 Mar 2026: Treatment of pulmonary neuroendocrine carcinoma; EU/3/13/1212 withdrawn 16 Jan 2014: Treatment of follicular lymphoma; EU/3/13/1203 withdrawn 13 Nov 2013: Treatment of diffuse large B-cell lymphoma; EU/3/16/1780 withdrawn 18 Nov 2016: Treatment of graft-versus-host disease; +4 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":"Opdivo: authorised since 19 Jun 2015; Imbruvica: authorised since 21 Oct 2014; Opdualag: authorised since 15 Sept 2022; Erbitux: authorised since 29 Jun 2004; +1 more","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":"Nivolumab and hyaluronidase-nvhy [Opdivo Quantig], 24 Nov 2025: Treatment of adult and pediatric patients 12 years and older who weigh 30 kg or greater with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC) following treatment with intravenous nivolumab and ipilimumab combination therapy; Nivolumab and hyaluronidase-nvhy [Opdivo Quantig], 24 Nov 2025: Treatment of adult and pediatric patients 12 years and older who weigh 30 kg or greater, with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan; Nivolumab and hyaluronidase-nvhy [Opdivo Quantig], 24 Nov 2025: Adjuvant treatment of adult and pediatric patients 12 years and older who weigh 30 kg or greater with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma; +7 more","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":"2026-11-11T17:04:05.822Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"163 interventional studies of Ibrutinib, Cetuximab, Nivolumab include patients under 18; 80 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=%22Ibrutinib%22+OR+%22Cetuximab%22+OR+%22Nivolumab%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-11T17:04:05.826Z"},"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":"University of California, San Diego (academic or other)","source":{"label":"ClinicalTrials.gov NCT03646461","url":"https://clinicaltrials.gov/study/NCT03646461","date":"2026-11-11T17:04:05.799Z"}},{"label":"principal investigator","text":"Kathryn Gold, MD, University of California San Diego, Moores Cancer Center","source":{"label":"Person page","url":"/person/Kathryn%20Gold%2C%20MD","date":"2026-11-11T17:04:05.799Z"}}],"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 NCT03646461","url":"https://clinicaltrials.gov/study/NCT03646461","date":"2026-11-11T17:04:05.799Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T17:04:05.799Z"},{"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":"2026-11-11T17:04:05.797Z"}