{"entity":{"id":"idea-bio2-gdf15-stratified-enrolment","kind":"idea","name":"Select cachexia trial patients by the hormone driving their wasting","aka":[],"tldr":"Wasting has several causes. Measuring the specific hormone in each patient's blood would put the right patients into the right trial instead of mixing everyone together.","summary":"Cachexia trials have historically enrolled by weight loss criteria alone, mixing inflammatory, anorexic, hypermetabolic and mechanical causes. Plasma GDF-15, interleukin-6, C-reactive protein and resting energy expenditure define mechanistically distinct groups. Enriching for high GDF-15 in anti-GDF-15 trials, and for high interleukin-6 in anti-inflammatory trials, is straightforward and cheap.","asOf":"2026-09-08","links":[{"label":"GDF15","url":"https://en.wikipedia.org/wiki/GDF15"}],"tags":[],"related":[],"cancers":["pancreatic","nsclc"],"sections":[],"technologies":["proteomics"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-biomarker-validation","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Biomarker-stratified enrolment increases the observed treatment effect size in cachexia trials by at least 50% relative to unselected enrolment, converting historically borderline results into clear ones.","rationale":"Mechanistic stratification rescued many oncology drugs that failed in unselected populations. Cachexia is arguably the least stratified field in oncology despite having measurable, causally relevant plasma markers.","test":"Retrospectively stratify banked samples from completed cachexia trials by GDF-15 and interleukin-6 and test for treatment-by-biomarker interaction; if present, mandate stratification prospectively.","maturity":"speculative","actor":"industry","cost":"small","horizonYears":4},"route":"/ideas/idea-bio2-gdf15-stratified-enrolment/","neighbours":{"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"proteomics","kind":"technology","name":"Proteomics & phosphoproteomics","route":"/technologies/proteomics/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-cachexia-supportive","kind":"bottleneck","name":"Cachexia, toxicity and the limits of the patient","route":"/bottlenecks/b-cachexia-supportive/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"trial":[{"id":"ponsegromab-phase-2","kind":"trial","name":"Ponsegromab phase 2 in cancer cachexia","route":"/trials/ponsegromab-phase-2/"}]}}