{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT06374459","title":"Zunsemetinib in Combination With Capecitabine in Patients With Hormone Receptor-Positive and HER2-Negative Metastatic Breast Cancer With Bone Metastasis","sponsor":"Washington University School of Medicine","phases":["PHASE1","PHASE2"],"status":"RECRUITING","indication":{"slug":"breast","name":"Breast cancer"},"disease":"breast carcinoma"},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"no","detail":"None of FDPS, TNFSF11 has somatic-mutation evidence in breast carcinoma","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: FDPS in breast carcinoma","url":"https://platform.opentargets.org/evidence/ENSG00000160752/MONDO_0004989","date":"2026-11-12T00:54:36.587Z"},"context":[]},{"id":"human_genetic","label":"Human genetic evidence","value":"no","detail":"No germline or somatic evidence for FDPS, TNFSF11 in breast 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: FDPS in breast carcinoma","url":"https://platform.opentargets.org/evidence/ENSG00000160752/MONDO_0004989","date":"2026-11-12T00:54:36.587Z"},"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":"no","detail":"Solid tumour","rule":"From the indication, or the registry conditions when no indication matches","source":{"label":"ClinicalTrials.gov NCT06374459","url":"https://clinicaltrials.gov/study/NCT06374459","date":"2026-11-12T00:54:36.587Z"},"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":"Capecitabine: standard agents, not counted in these flags."},{"label":"FDPS (via Zoledronic acid)","text":"Evidence types in breast carcinoma: literature; literature listed separately from human genetics. Datasources: europepmc.","source":{"label":"Open Targets: FDPS in breast carcinoma","url":"https://platform.opentargets.org/evidence/ENSG00000160752/MONDO_0004989","date":"2026-11-12T00:54:36.587Z"}},{"label":"TNFSF11 (via Denosumab)","text":"Evidence types in breast carcinoma: literature; literature listed separately from human genetics. Datasources: europepmc.","source":{"label":"Open Targets: TNFSF11 in breast carcinoma","url":"https://platform.opentargets.org/evidence/ENSG00000120659/MONDO_0004989","date":"2026-11-12T00:54:36.587Z"}}],"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 NCT06374459","url":"https://clinicaltrials.gov/study/NCT06374459","date":"2026-11-12T00:54:36.587Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"no","detail":"152 planned; each patient moves a rate by 100 ÷ 152 = 0.7 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT06374459","url":"https://clinicaltrials.gov/study/NCT06374459","date":"2026-11-12T00:54:36.587Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"no","detail":"Number of participants with adverse events (Phase Ib only); Recommended phase II dose of zunsemetinib (Phase Ib only); Number of participants with dose-limiting toxicities (Phase Ib only) (and 2 more)","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT06374459","url":"https://clinicaltrials.gov/study/NCT06374459","date":"2026-11-12T00:54:36.587Z"},"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 expected 2032-05-31; not yet due","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT06374459","url":"https://clinicaltrials.gov/study/NCT06374459","date":"2026-11-12T00:54:36.587Z"},"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":"90 terminated, withdrawn or suspended trials of drugs against FDPS; 27 give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"FDPS: what already stopped","url":"/target/ENSG00000160752#stopped","date":"2026-11-12T00:54:36.595Z"}}],"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 NCT06374459","url":"https://clinicaltrials.gov/study/NCT06374459?tab=locations","date":"2026-11-12T00:54:36.587Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMEA-000145-PIP02-12-M05 (denosumab, Treatment of osteoporosis): PM: decision on the application for modification of an agreed PIP, 14 Apr 2023; compliance positive 13 Dec 2024; EMEA-000145-PIP01-07-M09 (denosumab, Prevention of skeletal related events in patients with bone metastases;Treatment of bone loss associated with sex hormone ablative therapy;Treatment of chronic idiopathic arthritis (including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and juvenile idiopathic arthritis);Treatment of giant cell tumour of bone;Treatment of hypercalcemia of malignancy): PM: decision on the application for modification of an agreed PIP, 16 Mar 2018; compliance positive 1 Mar 2019; EMEA-000057-PIP01-07-M07 (zoledronic acid, Treatment of osteoporosis;Treatment of Paget’s disease of the bone): PM: decision on the application for modification of an agreed PIP, 17 Jan 2020; compliance positive 30 Apr 2020; EMEA-000024-PIP01-07 (zoledronic acid, Osteogenesis imperfecta;Prevention of fracture and bone loss in postmenopausal women with early-stage breast cancer treated with aromatase inhibitors;Prevention of skeletal related events in patients with advanced malignancies involving bone;Tumour-induced hypercalcaemia): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 24 Jun 2008; compliance positive 12 Dec 2008","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/3/16/1735 positive 29 Aug 2016: Treatment of glioma; EU/3/13/1192 positive 7 Oct 2013: Treatment of complex regional pain syndrome; - negative 17 Apr 2013: Treatment of complex regional pain syndrome; EU/3/10/748 positive 9 Jun 2010: Treatment of Hutchinson-Gilford progeria","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":"Bildyos: authorised since 17 Sept 2025; Jubereq: authorised since 26 May 2025; Yaxwer: authorised since 23 Jun 2025; Prolia: authorised since 26 May 2010; +38 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":"Denosumab [Xgeva], 13 Jun 2013: Treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity","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":"2026-11-12T00:54:36.604Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"76 interventional studies of Zumsemetinib, Zoledronic acid, Denosumab include patients under 18; 12 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=%22Zumsemetinib%22+OR+%22Zoledronic+acid%22+OR+%22Denosumab%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-12T00:54:36.604Z"},"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":"Washington University School of Medicine (academic or other)","source":{"label":"ClinicalTrials.gov NCT06374459","url":"https://clinicaltrials.gov/study/NCT06374459","date":"2026-11-12T00:54:36.587Z"}},{"label":"principal investigator","text":"Cynthia X Ma, M.D., Ph.D., Washington University School of Medicine","source":{"label":"Person page","url":"/person/Cynthia%20X%20Ma%2C%20M.D.%2C%20Ph.D.?ind=breast","date":"2026-11-12T00:54:36.587Z"}}],"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 NCT06374459","url":"https://clinicaltrials.gov/study/NCT06374459","date":"2026-11-12T00:54:36.587Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-12T00:54:36.587Z"},{"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":"2026-11-12T00:54:36.586Z"}