{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT07492641","title":"BGB-43395 Plus Letrozole Versus CDK4/6i Plus Letrozole for Patients With Advanced or Metastatic HR+/HER2- Breast Cancer Who Have Not Received Prior Treatment for Advanced or Metastatic Disease","sponsor":"BeOne Medicines","phases":["PHASE3"],"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":"yes","detail":"CDK4, CDK6, CCND1 in breast carcinoma","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: CDK4 in breast carcinoma","url":"https://platform.opentargets.org/evidence/ENSG00000135446/MONDO_0004989","date":"2026-11-11T18:15:33.397Z"},"context":[{"figure":"2.3× relative success for targets with somatic (IntOGen) support in oncology","dataset":"Minikel et al., Nature 2024","years":"drug programs to 2023","caveat":"A ratio between groups, not a probability for this program; mostly phase 2 to 3."}]},{"id":"human_genetic","label":"Human genetic evidence","value":"yes","detail":"CDK4: somatic; CDK6: somatic; CCND1: germline, somatic","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: CDK4 in breast carcinoma","url":"https://platform.opentargets.org/evidence/ENSG00000135446/MONDO_0004989","date":"2026-11-11T18:15:33.397Z"},"context":[{"figure":"2.6× relative probability of success, phase 1 to launch, with human genetic support","dataset":"Minikel et al., Nature 2024","years":"drug programs to 2023","caveat":"All therapy areas, mostly germline evidence; not a probability for this program."}]},{"id":"pediatric_target","label":"Pediatric target","value":"yes","detail":"CDK4, CDK6, CCND1 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 NCT07492641","url":"https://clinicaltrials.gov/study/NCT07492641","date":"2026-11-11T18:15:33.397Z"},"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":"CYP19A1 (via Letrozole)","text":"Evidence types in breast carcinoma: literature, rna_expression, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc, expression_atlas.","source":{"label":"Open Targets: CYP19A1 in breast carcinoma","url":"https://platform.opentargets.org/evidence/ENSG00000137869/MONDO_0004989","date":"2026-11-11T18:15:33.397Z"}},{"label":"CDK4 (via Abemaciclib)","text":"Evidence types in breast carcinoma: literature, affected_pathway, somatic_mutation, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, cancer_gene_census, crispr, europepmc.","source":{"label":"Open Targets: CDK4 in breast carcinoma","url":"https://platform.opentargets.org/evidence/ENSG00000135446/MONDO_0004989","date":"2026-11-11T18:15:33.397Z"}},{"label":"CDK6 (via Abemaciclib)","text":"Evidence types in breast carcinoma: literature, rna_expression, somatic_mutation, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, cancer_gene_census, europepmc, expression_atlas.","source":{"label":"Open Targets: CDK6 in breast carcinoma","url":"https://platform.opentargets.org/evidence/ENSG00000105810/MONDO_0004989","date":"2026-11-11T18:15:33.397Z"}},{"label":"CCND1 (via Palbociclib)","text":"Evidence types in breast carcinoma: rna_expression, clinical, affected_pathway, literature, genetic_association, somatic_mutation; literature listed separately from human genetics. Datasources: clinical_precedence, cancer_gene_census, crispr, gwas_credible_sets, europepmc, expression_atlas.","source":{"label":"Open Targets: CCND1 in breast carcinoma","url":"https://platform.opentargets.org/evidence/ENSG00000110092/MONDO_0004989","date":"2026-11-11T18:15:33.397Z"}}],"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 NCT07492641","url":"https://clinicaltrials.gov/study/NCT07492641","date":"2026-11-11T18:15:33.397Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"no","detail":"1056 planned; each patient moves a rate by 100 ÷ 1056 = 0.1 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT07492641","url":"https://clinicaltrials.gov/study/NCT07492641","date":"2026-11-11T18:15:33.397Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"no","detail":"Progression-Free Survival (PFS) Determined by Blinded Independent Central Review (BICR)","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT07492641","url":"https://clinicaltrials.gov/study/NCT07492641","date":"2026-11-11T18:15:33.397Z"},"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 2029-04; not yet due","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT07492641","url":"https://clinicaltrials.gov/study/NCT07492641","date":"2026-11-11T18:15:33.397Z"},"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":"165 terminated, withdrawn or suspended trials of drugs against CYP19A1; 19 give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"CYP19A1: what already stopped","url":"/target/ENSG00000137869#stopped","date":"2026-11-11T18:15:33.455Z"}}],"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":"241 sites in 16 countries; 84 in the United States (35%)","rule":"All listed sites are in one country; the share of US sites is shown","source":{"label":"ClinicalTrials.gov NCT07492641","url":"https://clinicaltrials.gov/study/NCT07492641?tab=locations","date":"2026-11-11T18:15:33.397Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMA/PE/0000228776 (abemaciclib, Treatment of glioma): PM: decision on the application for modification of an agreed PIP, 28 Jan 2025; EMEA-002342-PIP01-18-M04 (abemaciclib, Treatment of Ewing sarcoma): PM: decision on the application for modification of an agreed PIP, 7 Feb 2024; EMEA-002342-PIP05-23 (abemaciclib, Treatment of prostate cancer): W: decision granting a waiver in all age groups for all conditions or indications, 8 Sept 2023; EMEA-002146-PIP01-17-M04 (Palbociclib, Treatment of Ewing sarcoma): PM: decision on the application for modification of an agreed PIP, 13 Apr 2022; +2 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":"no","detail":"No EU orphan designation names BGB-43395, Letrozole, Abemaciclib, Palbociclib","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":"Palbociclib Viatris: authorised since 19 Jun 2026; Verzenios: authorised since 26 Sept 2018; Ibrance: authorised since 9 Nov 2016","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":"no","detail":"FDA's table lists no pediatric approval of BGB-43395, Letrozole, Abemaciclib, Palbociclib","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":"2026-11-11T18:15:33.475Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"65 interventional studies of BGB-43395, Letrozole, Abemaciclib, Palbociclib include patients under 18; 18 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=%22BGB-43395%22+OR+%22Letrozole%22+OR+%22Abemaciclib%22+OR+%22Palbociclib%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-11T18:15:33.479Z"},"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":"BeOne Medicines (industry)","source":{"label":"ClinicalTrials.gov NCT07492641","url":"https://clinicaltrials.gov/study/NCT07492641","date":"2026-11-11T18:15:33.397Z"}},{"label":"study director","text":"Study Director, BeOne Medicines","source":{"label":"Person page","url":"/person/Study%20Director?ind=breast","date":"2026-11-11T18:15:33.397Z"}}],"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 NCT07492641","url":"https://clinicaltrials.gov/study/NCT07492641","date":"2026-11-11T18:15:33.397Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T18:15:33.397Z"},{"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":"2026-11-11T18:15:33.390Z"}