{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT04854499","title":"Study of Magrolimab Combination Therapy in Patients With Head and Neck Squamous Cell Carcinoma","sponsor":"Gilead Sciences","phases":["PHASE2"],"status":"TERMINATED","indication":null,"disease":"head and neck squamous cell carcinoma"},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"no","detail":"None of CD47, PDCD1 has somatic-mutation evidence in head and neck squamous cell carcinoma","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: CD47 in head and neck squamous cell carcinoma","url":"https://platform.opentargets.org/evidence/ENSG00000196776/MONDO_0010150","date":"2026-11-11T17:38:09.713Z"},"context":[]},{"id":"human_genetic","label":"Human genetic evidence","value":"no","detail":"No germline or somatic evidence for CD47, PDCD1 in head and neck squamous cell carcinoma","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: CD47 in head and neck squamous cell carcinoma","url":"https://platform.opentargets.org/evidence/ENSG00000196776/MONDO_0010150","date":"2026-11-11T17:38:09.713Z"},"context":[]},{"id":"pediatric_target","label":"Pediatric target","value":"yes","detail":"CD47, 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 NCT04854499","url":"https://clinicaltrials.gov/study/NCT04854499","date":"2026-11-11T17:38:09.713Z"},"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":"Background therapy","text":"5-FU: standard agents, not counted in these flags."},{"label":"CD47 (via Magrolimab)","text":"Evidence types in head and neck squamous cell carcinoma: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc.","source":{"label":"Open Targets: CD47 in head and neck squamous cell carcinoma","url":"https://platform.opentargets.org/evidence/ENSG00000196776/MONDO_0010150","date":"2026-11-11T17:38:09.713Z"}},{"label":"PDCD1 (via Pembrolizumab)","text":"Evidence types in head and neck squamous cell carcinoma: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc.","source":{"label":"Open Targets: PDCD1 in head and neck squamous cell carcinoma","url":"https://platform.opentargets.org/evidence/ENSG00000188389/MONDO_0010150","date":"2026-11-11T17:38:09.713Z"}}],"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 NCT04854499","url":"https://clinicaltrials.gov/study/NCT04854499","date":"2026-11-11T17:38:09.713Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"no","detail":"193 enrolled; each patient moves a rate by 100 ÷ 193 = 0.5 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT04854499","url":"https://clinicaltrials.gov/study/NCT04854499","date":"2026-11-11T17:38:09.713Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"no","detail":"Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) According to t…; Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities; Phase 2 Cohort 1, Arms A and B: Progression-free Survival (PFS) (and 1 more)","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT04854499","url":"https://clinicaltrials.gov/study/NCT04854499","date":"2026-11-11T17:38:09.713Z"},"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 2025-11-19","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT04854499","url":"https://clinicaltrials.gov/study/NCT04854499?tab=results","date":"2026-11-11T17:38:09.713Z"},"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":"28 terminated, withdrawn or suspended trials of drugs against CD47. Reasons are quoted as the registry gives them on the target page.","source":{"label":"CD47: what already stopped","url":"/target/ENSG00000196776#stopped","date":"2026-11-11T17:38:09.725Z"}}],"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":"88 sites in 11 countries; 22 in the United States (25%)","rule":"All listed sites are in one country; the share of US sites is shown","source":{"label":"ClinicalTrials.gov NCT04854499","url":"https://clinicaltrials.gov/study/NCT04854499?tab=locations","date":"2026-11-11T17:38:09.713Z"},"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-002819-PIP01-20-M01 (Magrolimab, Treatment of acute myeloid leukaemia;Treatment of myelodysplastic syndromes, including juvenile myelomonocytic leukemia): PM: decision on the application for modification of an agreed PIP, 14 Jul 2023; 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; +8 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/3/25/3163 positive 12 Sept 2025: Treatment of oesophageal cancer; EU/3/25/3167 positive 12 Sept 2025: Treatment of gastric cancer; EU/3/20/2288 withdrawn 26 Jun 2020: Treatment of myelodysplastic syndromes; EU/3/15/1582 withdrawn 11 Nov 2015: Treatment of acute myeloid leukaemia","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","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 EPAR Keytruda","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/keytruda","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":"2026-11-11T17:38:09.745Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"76 interventional studies of Magrolimab, Pembrolizumab, Zimberelimab include patients under 18; 43 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=%22Magrolimab%22+OR+%22Pembrolizumab%22+OR+%22Zimberelimab%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-11T17:38:09.752Z"},"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":"Gilead Sciences (industry)","source":{"label":"ClinicalTrials.gov NCT04854499","url":"https://clinicaltrials.gov/study/NCT04854499","date":"2026-11-11T17:38:09.713Z"}},{"label":"study director","text":"Gilead Study Director, Gilead Sciences","source":{"label":"Person page","url":"/person/Gilead%20Study%20Director","date":"2026-11-11T17:38:09.713Z"}}],"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 NCT04854499","url":"https://clinicaltrials.gov/study/NCT04854499","date":"2026-11-11T17:38:09.713Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T17:38:09.713Z"},{"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":"2026-11-11T17:38:09.710Z"}