Melphalan/HDS treatment for patients with hepatic dominant metastatic uveal melanoma: Results from an expanded access program.

e21519 Background: Uveal melanoma has a poor prognosis once liver metastases occur. Melphalan/Hepatic Delivery System (Melphalan/HDS) is a drug/device combination therapy used for liver-directed treatment of metastatic UM (mUM) patients. The purpose of the Expanded Access Program (EAP) was to provide access to Melphalan/HDS in patients with unresectable mUM and to assess safety and efficacy. Methods: In the EAP 15 eligible patients with unresectable mUM were treated with Melphalan/HDS at 4 institutions. The primary objective was to provide access to Melphalan/HDS treatment to mUM patients. Secondary objectives included evaluation of safety, objective response rate (ORR), duration of response (DOR) and progression-free survival (PFS). Melphalan/HDS treatment was administered every 6-8 weeks for a maximum of 6 cycles with imaging every 12 weeks. Melphalan dose was 3 mg/kg ideal body weight. Results: The median age was 62 years (range 32-78), male 9 (60%) female 6 (40%), treatment naïve 8 (53.3%) previously treated 7 (46.7%), hepatic only metastases 12 (80%) hepatic and extrahepatic metastases 3 (20%). The 15 patients received a total of 59 treatment cycles and the median number of cycles received was 4. Four patients discontinued from study treatment as they transferred to standard of care (SOC) treatment with Melphalan/HDS once it became available outside the EAP at their treating institution. Grade 3 or 4 SAEs occurred in 3 (20%) patients with 1 patient having thrombocytopenia and febrile neutropenia, 1 patient having pulmonary edema and 1 patient having ventricular tachycardia. Efficacy analysis was conducted on 13 patients as 2 patients transferred to SOC did not have follow-up imaging prior to transfer. ORR was 46.2% (95% CI: 19.22-74.87) confirmed by repeat assessment at the next scheduled imaging timepoint. Median DOR was 11.29 months (95% CI: 8.38-NC). In the DOR analysis 2 of the 6 patients (33.3%) were censored. Median PFS was 14.2 months (95% CI: 2.89-NC). In the PFS analysis 6 of 13 patients (46.2%) were censored. The disease control rate (DCR) was 92.3%. Conclusions: Treatment with Melphalan/HDS provides a clinically meaningful response rate and demonstrates a favorable benefit-risk profile in patients with unresectable mUM. Toxicities were manageable and overall treatment with Melphalan/HDS was well tolerated. Clinical trial information: NCT05022901 . Best overall response. Best Overall Response EAP Patients (n = 13)n (%) CR 1 (7.7) PR 5 (38.5) SD 6 (46.2) PD 1 (7.7)