{"entity":{"id":"nct02678572","kind":"trial","name":"FOCUS","aka":["PHP-OCM-301A","PHP-OCM-301","Percutaneous Hepatic Perfusion in Patients With Hepatic-dominant Ocular Melanoma"],"tldr":"FOCUS showed that pumping high-dose melphalan through the liver's blood supply, then filtering it out before the blood returns to the body, shrank tumours in about one in three patients whose eye melanoma had spread to the liver, and it supported the treatment's US approval in 2023.","summary":"FOCUS was an open-label phase 3 trial of melphalan delivered by percutaneous hepatic perfusion with the Hepatic Delivery System in patients with unresectable metastatic uveal melanoma and liver-dominant disease. Of 102 patients enrolled, treatment was attempted in 95 and 91 received it. Melphalan 3 mg per kg ideal body weight was given once every 6 to 8 weeks for up to six cycles. The primary endpoint was objective response rate by independent central review, judged against the upper confidence bound of a benchmark meta-analysis. The registry's outcome definitions date events from the eligibility date for PHP-OCM-301A patients and from the randomisation date for PHP-OCM-301 patients, the trace of an earlier randomised phase of the same study.\n\nIn the 91 treated patients the objective response rate was 36.3 percent (95% CI 26.44 to 47.01), including complete responses in 7.7 percent. The lower confidence bound exceeded the 8.3 percent benchmark, so the study met its primary endpoint. Median duration of response was 14 months, median overall survival 20.5 months (80 percent alive at 1 year) and median progression-free survival 9 months (65 percent progression-free at 6 months). The most common serious treatment-emergent adverse events were thrombocytopenia (15.8 percent) and neutropenia (10.5 percent), and there were no treatment-related deaths (Annals of Surgical Oncology 2024). The registry results section adds a disease control rate of 73.6 percent and gives the duration-of-response median as 14.00 months (95% CI 8.31 to 17.74).\n\nFOCUS is the efficacy trial in the US label of the Hepzato Kit, approved in August 2023, whose Table 4 reports the same 36.3 percent response (complete 7.7 percent, partial 28.6 percent) and a median duration of response of 14.0 months among 33 responders. Its result is judged against a historical benchmark rather than a concurrent control, and it did not compare liver-directed treatment with tebentafusp, which improved overall survival in HLA-A*02:01-positive metastatic uveal melanoma in IMCgp100-202.","status":"positive","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov NCT02678572","url":"https://clinicaltrials.gov/study/NCT02678572"},{"label":"Annals of Surgical Oncology 2024","url":"https://doi.org/10.1245/s10434-024-15293-x"},{"label":"Hepzato Kit label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4f83c8f7-4cc0-4219-88d5-7cfddce91198"}],"tags":[],"related":["imcgp100-202","nct06519266"],"cancers":["uveal-melanoma"],"sections":[],"technologies":["percutaneous-hepatic-perfusion"],"targets":[],"drugs":["hepzato","melphalan"],"companies":["delcath"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["reinhard-dummer"],"bottlenecks":[],"keyPapers":["paper-zager-ann-surg-oncol"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02678572","phase":"3","setting":"Unresectable liver-dominant metastatic uveal melanoma: melphalan by percutaneous hepatic perfusion with the Hepatic Delivery System, single arm, judged against a historical benchmark","sponsor":"Delcath Systems Inc.","result":"Objective response rate 36.3% by independent central review in 91 treated patients (complete response 7.7%), above the prespecified historical benchmark; median duration of response 14 months and median overall survival 20.5 months.","started":"2016-02-01","startedType":"actual","yearReported":2024,"enrolled":102,"enrolledBasis":"registry","outcomes":[{"endpoint":"Objective response rate (independent central review, treated population)","primary":true,"unit":"%","arms":[{"name":"Melphalan / Hepatic Delivery System","n":91,"value":36.3,"note":"95% CI 26.44 to 47.01; complete response 7.7%"}],"source":"https://doi.org/10.1245/s10434-024-15293-x"},{"endpoint":"Duration of response (independent central review)","unit":"months","arms":[{"name":"Melphalan / Hepatic Delivery System","n":33,"value":14,"note":"Responders only (33 in the US label Table 4)"}],"source":"https://doi.org/10.1245/s10434-024-15293-x"},{"endpoint":"Progression-free survival (treated population)","unit":"months","arms":[{"name":"Melphalan / Hepatic Delivery System","n":91,"value":9,"note":"65% progression-free at 6 months"}],"source":"https://doi.org/10.1245/s10434-024-15293-x"},{"endpoint":"Overall survival (treated population)","unit":"months","arms":[{"name":"Melphalan / Hepatic Delivery System","n":91,"value":20.5,"note":"80% alive at 1 year"}],"source":"https://doi.org/10.1245/s10434-024-15293-x"},{"endpoint":"Disease control rate (independent central review, treated population)","unit":"%","arms":[{"name":"Melphalan / Hepatic Delivery System","n":91,"value":73.6,"note":"95% CI 63.35 to 82.31; registry results section"}],"source":"https://clinicaltrials.gov/study/NCT02678572?tab=results"}],"replication":"Single-arm result judged against a historical benchmark; the randomised phase 3 NCT06519266 tests percutaneous hepatic perfusion added to ipilimumab and nivolumab against ipilimumab and nivolumab alone."},"route":"/trials/nct02678572/","neighbours":{"trial":[{"id":"imcgp100-202","kind":"trial","name":"IMCgp100-202","route":"/trials/imcgp100-202/"},{"id":"nct06519266","kind":"trial","name":"PHP in Combination With IPI1/NIVO3 Compared to IPI3/NIVO1 Only in Patients With Uveal Melanoma Liver Metastases","route":"/trials/nct06519266/"}],"cancer":[{"id":"uveal-melanoma","kind":"cancer","name":"Uveal melanoma","route":"/cancers/uveal-melanoma/"}],"technology":[{"id":"percutaneous-hepatic-perfusion","kind":"technology","name":"Percutaneous hepatic perfusion (chemosaturation)","route":"/technologies/percutaneous-hepatic-perfusion/"}],"drug":[{"id":"melphalan","kind":"drug","name":"Melphalan (including hepatic delivery system)","route":"/drugs/melphalan/"},{"id":"hepzato","kind":"drug","name":"Melphalan hepatic delivery system","route":"/drugs/hepzato/"}],"company":[{"id":"delcath","kind":"company","name":"Delcath Systems","route":"/companies/delcath/"}],"person":[{"id":"reinhard-dummer","kind":"person","name":"Reinhard Dummer","route":"/people/reinhard-dummer/"}],"paper":[{"id":"paper-zager-ann-surg-oncol","kind":"paper","name":"Efficacy and Safety of the Melphalan/Hepatic Delivery System in Patients with Unresectable Metastatic Uveal Melanoma: Results from an Open-Label, Single-Arm, Multicenter Phase 3 Study","route":"/key-papers/paper-zager-ann-surg-oncol/"}]}}