{"entity":{"id":"splash","kind":"trial","name":"SPLASH","aka":[],"tldr":"In SPLASH, a second PSMA radioligand improved progression-free survival but not, so far, survival.","summary":"SPLASH, trial NCT04647526 sponsored by Lantheus through POINT Biopharma and reported in 2024, tested a second PSMA radioligand, 177Lu-PNT2002, also known as 177Lu-PSMA-I&T, against a switch of androgen receptor pathway inhibitor in PSMA-positive, taxane-naive metastatic castration-resistant prostate cancer. It randomised 412 men and met its primary radiographic progression-free survival endpoint, but the interim overall survival analysis was numerically unfavourable, with 46 percent of events and 84 percent crossover, and Lantheus deprioritised a US filing pending mature data. OnCo links it to prostate cancer and to the 177Lu-PSMA-I&T drug record; its effect was smaller than PSMAfore's with a different ligand and dosing, while ECLIPSE with the same ligand met its progression endpoint. Whether crossover masked a real benefit or the drug simply adds little is the open question.","status":"mixed","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT04647526","url":"https://clinicaltrials.gov/study/NCT04647526"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":["lu177-psma-it"],"companies":["lantheus"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-splash-front-oncol-2024"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04647526","phase":"3","setting":"PSMA-positive mCRPC after one ARPI, taxane-naive: 177Lu-PNT2002 vs ARPI switch","sponsor":"Lantheus (POINT Biopharma)","result":"rPFS HR 0.71; interim OS HR 1.11.","started":"2021-02-25","startedType":"actual","yearReported":2024,"enrolled":455,"enrolledBasis":"registry","outcomes":[{"endpoint":"Radiographic progression-free survival","primary":true,"unit":"months","arms":[{"name":"177Lu-PNT2002 (PSMA-I&T)","n":276,"value":9.5},{"name":"ARPI switch","n":136,"value":6}],"hr":0.71,"ci":[0.55,0.92],"p":"0.0088","source":"https://clinicaltrials.gov/study/NCT04647526"},{"endpoint":"Overall survival (interim)","unit":"months","arms":[{"name":"177Lu-PNT2002","note":"Numerically unfavourable at interim with crossover"},{"name":"ARPI switch"}],"hr":1.11,"source":"https://clinicaltrials.gov/study/NCT04647526"}],"replication":"Smaller effect than PSMAfore (rPFS HR 0.41) with a different ligand and dosing; ECLIPSE (177Lu-PSMA-I&T) met rPFS."},"route":"/trials/splash/","neighbours":{"cancer":[{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"radioligand-therapy","kind":"technology","name":"Radioligand therapy (beta emitters)","route":"/technologies/radioligand-therapy/"}],"drug":[{"id":"lu177-psma-it","kind":"drug","name":"177Lu-PSMA-I&T","route":"/drugs/lu177-psma-it/"}],"company":[{"id":"lantheus","kind":"company","name":"Lantheus","route":"/companies/lantheus/"}],"paper":[{"id":"paper-splash-front-oncol-2024","kind":"paper","name":"Initial clinical experience with [ 177 Lu]Lu-PNT2002 radioligand therapy in metastatic castration-resistant prostate cancer: dosimetry, safety, and efficacy from the lead-in cohort of the SPLASH trial","route":"/key-papers/paper-splash-front-oncol-2024/"}]}}