{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT04246177","title":"Safety and Efficacy of Lenvatinib (E7080/MK-7902) With Pembrolizumab (MK-3475) in Combination With Transarterial Chemoembolization (TACE) in Participants With Incurable/Non-metastatic Hepatocellular Carcinoma (MK-7902-012/E7080-G000-318/LEAP-012)","sponsor":"Merck Sharp & Dohme LLC","phases":["PHASE3"],"status":"TERMINATED","indication":null,"disease":"hepatobiliary disorder"},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"no","detail":"None of FLT1, FLT4, KDR, PDCD1 has somatic-mutation evidence in hepatobiliary disorder","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: FLT1 in hepatobiliary disorder","url":"https://platform.opentargets.org/evidence/ENSG00000102755/MONDO_0002515","date":"2026-11-11T20:58:28.893Z"},"context":[]},{"id":"human_genetic","label":"Human genetic evidence","value":"no","detail":"No germline or somatic evidence for FLT1, FLT4, KDR, PDCD1 in hepatobiliary disorder","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: FLT1 in hepatobiliary disorder","url":"https://platform.opentargets.org/evidence/ENSG00000102755/MONDO_0002515","date":"2026-11-11T20:58:28.893Z"},"context":[]},{"id":"pediatric_target","label":"Pediatric target","value":"yes","detail":"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 NCT04246177","url":"https://clinicaltrials.gov/study/NCT04246177","date":"2026-11-11T20:58:28.893Z"},"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":"FLT1 (via Lenvatinib)","text":"Open Targets has no association between FLT1 and hepatobiliary disorder.","source":{"label":"Open Targets: FLT1 in hepatobiliary disorder","url":"https://platform.opentargets.org/evidence/ENSG00000102755/MONDO_0002515","date":"2026-11-11T20:58:28.893Z"}},{"label":"FLT4 (via Lenvatinib)","text":"Open Targets has no association between FLT4 and hepatobiliary disorder.","source":{"label":"Open Targets: FLT4 in hepatobiliary disorder","url":"https://platform.opentargets.org/evidence/ENSG00000037280/MONDO_0002515","date":"2026-11-11T20:58:28.893Z"}},{"label":"KDR (via Lenvatinib)","text":"Evidence types in hepatobiliary disorder: literature; literature listed separately from human genetics. Datasources: europepmc.","source":{"label":"Open Targets: KDR in hepatobiliary disorder","url":"https://platform.opentargets.org/evidence/ENSG00000128052/MONDO_0002515","date":"2026-11-11T20:58:28.893Z"}},{"label":"PDCD1 (via Pembrolizumab)","text":"Evidence types in hepatobiliary disorder: literature; literature listed separately from human genetics. Datasources: europepmc.","source":{"label":"Open Targets: PDCD1 in hepatobiliary disorder","url":"https://platform.opentargets.org/evidence/ENSG00000188389/MONDO_0002515","date":"2026-11-11T20:58:28.893Z"}}],"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 NCT04246177","url":"https://clinicaltrials.gov/study/NCT04246177","date":"2026-11-11T20:58:28.893Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"no","detail":"480 enrolled; each patient moves a rate by 100 ÷ 480 = 0.2 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT04246177","url":"https://clinicaltrials.gov/study/NCT04246177","date":"2026-11-11T20:58:28.893Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"yes","detail":"Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed…; Overall Survival (OS)","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT04246177","url":"https://clinicaltrials.gov/study/NCT04246177","date":"2026-11-11T20:58:28.893Z"},"context":[]},{"id":"results_overdue","label":"Results overdue","value":"no","detail":"Results posted 2026-09-03","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT04246177","url":"https://clinicaltrials.gov/study/NCT04246177?tab=results","date":"2026-11-11T20:58:28.893Z"},"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":"450 terminated, withdrawn or suspended trials of drugs against FLT1; 16 of the 200 most recent give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"FLT1: what already stopped","url":"/target/ENSG00000102755#stopped","date":"2026-11-11T20:58:28.916Z"}}],"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":"205 sites in 27 countries; 27 in the United States (13%)","rule":"All listed sites are in one country; the share of US sites is shown","source":{"label":"ClinicalTrials.gov NCT04246177","url":"https://clinicaltrials.gov/study/NCT04246177?tab=locations","date":"2026-11-11T20:58:28.893Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMEA-003104-PIP02-22 (Favezelimab;pembrolizumab, Treatment of Hodgkin lymphoma): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), date not given; EMEA-003063-PIP03-22 (vibostolimab;pembrolizumab, Treatment of melanoma): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 27 Oct 2023; EMEA-003063-PIP02-22 (vibostolimab;pembrolizumab, Treatment of Hodgkin lymphoma): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), date not given; 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; +7 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/3/15/1460 withdrawn 19 Mar 2015: Treatment of hepatocellular carcinoma; EU/3/13/1121 withdrawn 26 Apr 2013: Treatment of papillary thyroid cancer; EU/3/13/1119 withdrawn 26 Apr 2013: Treatment of follicular thyroid cancer","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":"Keytruda: authorised since 17 Jul 2015; 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":"Pembrolizumab and berahyaluronidase alfa-pmph [Keytruda Qlex], 19 Sept 2025: Treatment of adult and pediatric patients 12 years and older with unresectable or metastatic tumor mutational burden high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options; Pembrolizumab and berahyaluronidase alfa-pmph [Keytruda Qlex], 19 Sept 2025: Adjuvant treatment of adult and pediatric patients 12 years and older with Stage IIB, IIC, or III melanoma following complete resection; Pembrolizumab and berahyaluronidase alfa-pmph [Keytruda Qlex], 19 Sept 2025: Treatment of adult and pediatric patients 12 years and older with unresectable or metastatic microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options; +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":"2026-11-11T20:58:28.944Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"90 interventional studies of Lenvatinib, Pembrolizumab include patients under 18; 49 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=%22Lenvatinib%22+OR+%22Pembrolizumab%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-11T20:58:28.959Z"},"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":"Merck Sharp & Dohme LLC (industry)","source":{"label":"ClinicalTrials.gov NCT04246177","url":"https://clinicaltrials.gov/study/NCT04246177","date":"2026-11-11T20:58:28.893Z"}},{"label":"study director","text":"Medical Director, Merck Sharp & Dohme LLC","source":{"label":"Person page","url":"/person/Medical%20Director","date":"2026-11-11T20:58:28.893Z"}}],"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 NCT04246177","url":"https://clinicaltrials.gov/study/NCT04246177","date":"2026-11-11T20:58:28.893Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T20:58:28.893Z"},{"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":"2026-11-11T20:58:28.890Z"}