{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT02744612","title":"Ibrutinib and Brentuximab Vedotin in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma","sponsor":"City of Hope Medical Center","phases":["PHASE2"],"status":"COMPLETED","indication":null,"disease":"hyper-IgE recurrent infection syndrome 1, autosomal dominant"},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"no","detail":"None of TUBB4B, TUBB1, TUBA3C, BTK has somatic-mutation evidence in hyper-IgE recurrent infection syndrome 1, autosomal dominant","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: TUBB4B in hyper-IgE recurrent infection syndrome 1, autosomal dominant","url":"https://platform.opentargets.org/evidence/ENSG00000188229/MONDO_0007818","date":"2026-11-11T19:51:23.645Z"},"context":[]},{"id":"human_genetic","label":"Human genetic evidence","value":"no","detail":"No germline or somatic evidence for TUBB4B, TUBB1, TUBA3C, BTK in hyper-IgE recurrent infection syndrome 1, autosomal dominant","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: TUBB4B in hyper-IgE recurrent infection syndrome 1, autosomal dominant","url":"https://platform.opentargets.org/evidence/ENSG00000188229/MONDO_0007818","date":"2026-11-11T19:51:23.645Z"},"context":[]},{"id":"pediatric_target","label":"Pediatric target","value":"no","detail":"Not 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":"yes","detail":"Haematologic","rule":"From the indication, or the registry conditions when no indication matches","source":{"label":"ClinicalTrials.gov NCT02744612","url":"https://clinicaltrials.gov/study/NCT02744612","date":"2026-11-11T19:51:23.645Z"},"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":"TUBB4B (via Brentuximab Vedotin)","text":"Open Targets has no association between TUBB4B and hyper-IgE recurrent infection syndrome 1, autosomal dominant.","source":{"label":"Open Targets: TUBB4B in hyper-IgE recurrent infection syndrome 1, autosomal dominant","url":"https://platform.opentargets.org/evidence/ENSG00000188229/MONDO_0007818","date":"2026-11-11T19:51:23.645Z"}},{"label":"TUBB1 (via Brentuximab Vedotin)","text":"Open Targets has no association between TUBB1 and hyper-IgE recurrent infection syndrome 1, autosomal dominant.","source":{"label":"Open Targets: TUBB1 in hyper-IgE recurrent infection syndrome 1, autosomal dominant","url":"https://platform.opentargets.org/evidence/ENSG00000101162/MONDO_0007818","date":"2026-11-11T19:51:23.645Z"}},{"label":"TUBA3C (via Brentuximab Vedotin)","text":"Open Targets has no association between TUBA3C and hyper-IgE recurrent infection syndrome 1, autosomal dominant.","source":{"label":"Open Targets: TUBA3C in hyper-IgE recurrent infection syndrome 1, autosomal dominant","url":"https://platform.opentargets.org/evidence/ENSG00000198033/MONDO_0007818","date":"2026-11-11T19:51:23.645Z"}},{"label":"BTK (via Ibrutinib)","text":"Open Targets has no association between BTK and hyper-IgE recurrent infection syndrome 1, autosomal dominant.","source":{"label":"Open Targets: BTK in hyper-IgE recurrent infection syndrome 1, autosomal dominant","url":"https://platform.opentargets.org/evidence/ENSG00000010671/MONDO_0007818","date":"2026-11-11T19:51:23.645Z"}}],"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":"Non-randomised","rule":"Registry allocation field","source":{"label":"ClinicalTrials.gov NCT02744612","url":"https://clinicaltrials.gov/study/NCT02744612","date":"2026-11-11T19:51:23.645Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"no","detail":"39 enrolled; each patient moves a rate by 100 ÷ 39 = 2.6 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT02744612","url":"https://clinicaltrials.gov/study/NCT02744612","date":"2026-11-11T19:51:23.645Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"no","detail":"Complete Response (CR) Rate","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT02744612","url":"https://clinicaltrials.gov/study/NCT02744612","date":"2026-11-11T19:51:23.645Z"},"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 2023-07-10","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT02744612","url":"https://clinicaltrials.gov/study/NCT02744612?tab=results","date":"2026-11-11T19:51:23.645Z"},"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":"362 terminated, withdrawn or suspended trials of drugs against TUBB4B; 18 of the 200 most recent give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"TUBB4B: what already stopped","url":"/target/ENSG00000188229#stopped","date":"2026-11-11T19:51:23.679Z"}}],"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":"All 3 sites in United States","rule":"All listed sites are in one country; the share of US sites is shown","source":{"label":"ClinicalTrials.gov NCT02744612","url":"https://clinicaltrials.gov/study/NCT02744612?tab=locations","date":"2026-11-11T19:51:23.645Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMEA-001397-PIP04-17-M02 (Ibrutinib, Treatment of chronic Graft versus Host Disease (cGvHD)): PM: decision on the application for modification of an agreed PIP, 11 Aug 2023; EMEA-000980-PIP01-10-M07 (Brentuximab vedotin, Treatment of anaplastic large cell lymphoma;Treatment of Hodgkin lymphoma): PM: decision on the application for modification of an agreed PIP, 28 Jan 2021; compliance positive 25 Jun 2021; EMEA-001397-PIP03-14-M06 (Ibrutinib, Treatment of mature B-cell neoplasms): PM: decision on the application for modification of an agreed PIP, 11 Aug 2021; compliance positive 25 Feb 2022; EMEA-000980-PIP04-18 (Brentuximab vedotin, Treatment of Mature T and NK neoplasms (excluding anaplastic large-cell lymphoma and cutaneous Tcell lymphoma)): W: decision granting a waiver in all age groups for all conditions or indications, 8 Oct 2018; +5 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/3/11/939 withdrawn 11 Jan 2012: Treatment of cutaneous T-cell lymphoma; EU/3/08/596 withdrawn 15 Jan 2009: Treatment of Hodgkin's lymphoma; 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; +5 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":"Imbruvica: authorised since 21 Oct 2014; Adcetris: authorised since 25 Oct 2012","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":"Brentuximab vedotin [Adcetris], 10 Nov 2022: Treatment of pediatric patients 2 years and older with previously untreated high risk classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide","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":"2026-11-11T19:51:23.697Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"60 interventional studies of Brentuximab Vedotin, Ibrutinib include patients under 18; 23 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=%22Brentuximab+Vedotin%22+OR+%22Ibrutinib%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-11T19:51:23.703Z"},"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":"City of Hope Medical Center (academic or other)","source":{"label":"ClinicalTrials.gov NCT02744612","url":"https://clinicaltrials.gov/study/NCT02744612","date":"2026-11-11T19:51:23.645Z"}},{"label":"principal investigator","text":"Alex Herrera, City of Hope Medical Center","source":{"label":"Person page","url":"/person/Alex%20Herrera","date":"2026-11-11T19:51:23.645Z"}}],"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 NCT02744612","url":"https://clinicaltrials.gov/study/NCT02744612","date":"2026-11-11T19:51:23.645Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T19:51:23.645Z"},{"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":"2026-11-11T19:51:23.641Z"}