{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT03520946","title":"RAMucirumab in Combination Wth TAS102 vs. TAS102 Alone in Chemotherapy Refractory Metastatic Colorectal Cancer Patients","sponsor":"Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest","phases":["PHASE3"],"status":"COMPLETED","indication":{"slug":"colorectal","name":"Colorectal cancer"},"disease":"colorectal cancer"},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"no","detail":"None of KDR has somatic-mutation evidence in colorectal cancer","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: KDR in colorectal cancer","url":"https://platform.opentargets.org/evidence/ENSG00000128052/MONDO_0005575","date":"2026-11-11T23:22:55.091Z"},"context":[]},{"id":"human_genetic","label":"Human genetic evidence","value":"no","detail":"No germline or somatic evidence for KDR in colorectal cancer","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: KDR in colorectal cancer","url":"https://platform.opentargets.org/evidence/ENSG00000128052/MONDO_0005575","date":"2026-11-11T23:22:55.091Z"},"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 NCT03520946","url":"https://clinicaltrials.gov/study/NCT03520946","date":"2026-11-11T23:22:55.091Z"},"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":"KDR (via Ramucirumab)","text":"Evidence types in colorectal cancer: literature, rna_expression, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc, expression_atlas.","source":{"label":"Open Targets: KDR in colorectal cancer","url":"https://platform.opentargets.org/evidence/ENSG00000128052/MONDO_0005575","date":"2026-11-11T23:22:55.091Z"}}],"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 NCT03520946","url":"https://clinicaltrials.gov/study/NCT03520946","date":"2026-11-11T23:22:55.091Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"no","detail":"430 enrolled; each patient moves a rate by 100 ÷ 430 = 0.2 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT03520946","url":"https://clinicaltrials.gov/study/NCT03520946","date":"2026-11-11T23:22:55.091Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"yes","detail":"Overall survival","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT03520946","url":"https://clinicaltrials.gov/study/NCT03520946","date":"2026-11-11T23:22:55.091Z"},"context":[]},{"id":"results_overdue","label":"Results overdue","value":"yes","detail":"Primary completion 2024-07-30, 27 months ago; no results posted","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT03520946","url":"https://clinicaltrials.gov/study/NCT03520946","date":"2026-11-11T23:22:55.091Z"},"context":[{"figure":"40.9% of applicable trials report results within a year","dataset":"Results-reporting studies summarised in spec §11","years":"all therapy areas","caveat":"All areas, not oncology only."}]}],"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":"382 terminated, withdrawn or suspended trials of drugs against KDR; 11 of the 200 most recent give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"KDR: what already stopped","url":"/target/ENSG00000128052#stopped","date":"2026-11-11T23:22:55.104Z"}}],"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 28 sites in Germany","rule":"All listed sites are in one country; the share of US sites is shown","source":{"label":"ClinicalTrials.gov NCT03520946","url":"https://clinicaltrials.gov/study/NCT03520946?tab=locations","date":"2026-11-11T23:22:55.091Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMEA-002074-PIP01-16 (ramucirumab, Treatment of gastric cancer and gastro-oesophageal junction adenocarcinoma;Treatment of intestinal malignant neoplasms;Treatment of liver cancer;Treatment of lung malignant neoplasms;Treatment of urinary tract malignant neoplasm): W: decision granting a waiver in all age groups for all conditions or indications, 4 Oct 2017","rule":"An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name","source":{"label":"EMA EMEA-002074-PIP01-16","url":"https://www.ema.europa.eu/en/medicines/human/paediatric-investigation-plans/emea-002074-pip01-16","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"eu_orphan","label":"EU orphan designation","value":"yes","detail":"EU/3/12/1019 withdrawn 4 Jul 2012: Treatment of hepatocellular carcinoma; EU/3/12/1004 withdrawn 4 Jul 2012: Treatment of gastric 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":"Cyramza: authorised since 19 Dec 2014","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 Cyramza","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/cyramza","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 Ramucirumab, TAS 102","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":"2026-11-11T23:22:55.120Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"12 interventional studies of Ramucirumab, TAS 102 include patients under 18; 6 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=%22Ramucirumab%22+OR+%22TAS+102%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-11T23:22:55.128Z"},"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":"Cited case","text":"In February 2022 FDA asked its Oncologic Drugs Advisory Committee whether sintilimab's application, resting on ORIENT-11, a phase 3 run only in China, needed further trials showing it applies to US patients and US practice. One case, not a rule.","source":{"label":"FDA, ODAC 10 Feb 2022, draft questions","url":"https://www.fda.gov/media/156017/download","date":"2022-02-10"}},{"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":"Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest (academic or other)","source":{"label":"ClinicalTrials.gov NCT03520946","url":"https://clinicaltrials.gov/study/NCT03520946","date":"2026-11-11T23:22:55.091Z"}},{"label":"study chair","text":"Salah-Eddin Al-Batran, Prof. Dr., Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest","source":{"label":"Person page","url":"/person/Salah-Eddin%20Al-Batran%2C%20Prof.%20Dr.?ind=colorectal","date":"2026-11-11T23:22:55.091Z"}}],"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 NCT03520946","url":"https://clinicaltrials.gov/study/NCT03520946","date":"2026-11-11T23:22:55.091Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-11T23:22:55.091Z"},{"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":"2026-11-11T23:22:55.088Z"}