1127P - Subgroup analysis of FOCUS phase III trial efficacy results

Background

The majority of metastatic uveal melanoma (mUM) patients require liver-directed therapy at some point in the course of their disease. Melphalan/Hepatic Delivery System (melphalan/HDS) is a drug/medical device combination that was recently approved by FDA for liver-directed treatment of unresectable mUM patients. The phase III FOCUS study demonstrated efficacy and safety of melphalan/HDS in a heterogenous patient population with unresectable mUM. Here we present efficacy analyses in clinically important subgroups.

Methods

Eligible patients with unresectable liver metastases from mUM, with or without extrahepatic disease, received treatment with percutaneous hepatic perfusion (PHP) of melphalan (3.0 mg/kg ideal body weight) once every 6-8 weeks for a maximum of 6 cycles. Efficacy endpoints including objective response rate (ORR), progression-free survival (PFS), overall survival (OS), were assessed among subgroups of patients with and without extrahepatic disease, previously treated and treatment-naive patients, and those with low (1-25%) and high (26-50%) liver tumor burden. Onset of ORR, serious adverse events (SAEs) and Grade 3/4 adverse events (AE) were assessed by treatment cycle.

Results

102 patients with mUM were enrolled; treatment was attempted in 95 patients, and 91 patients received treatment. Across the 6 subgroups, ORR ranged from 31.6% to 37.5%, median PFS ranged from 6.2 to 9.3 months, and median OS ranged from 16.9 to 22.4 months. 57.6% of tumor responses were observed in the first two treatment cycles. The percentages of patients who experienced SAEs in treatment cycles 1-6 were 22%, 15.5%, 13.6%, 5.5%, 7.5% and 17.6%, respectively, of the patients treated in each cycle; by-cycle percentages for Grade 3/4 AEs were 53.8%, 57.1%, 53%, 45.5%, 50% and 47.1%, respectively.

Conclusions

Treatment with melphalan/HDS provides clinically meaningful efficacy across the evaluated subgroups. Objective tumor responses occurred throughout all 6 treatment cycles, without evidence of cumulative toxicity.

Clinical trial identification

NCT02678572; EudraCT 2015-000417-44.

Editorial acknowledgement

Legal entity responsible for the study

Delcath Systems, Inc.

Funding

Delcath Systems, Inc.

Disclosure

M. Wheater: Financial Interests, Personal, Advisory Board: Delcath Systems. M. Orloff: Financial Interests, Personal, Advisory Board: Delcath Systems, Replimune; Financial Interests, Personal, Speaker, Consultant, Advisor: Immunocore; Financial Interests, Personal, Steering Committee Member: Ideaya. D. Eschelman: Financial Interests, Personal, Speaker, Consultant, Advisor: Delcath Systems. S. Ochsenreither: Financial Interests, Personal, Speaker, Consultant, Advisor: Immunocore, Delcath Systems, Janssen; Financial Interests, Personal, Speaker’s Bureau: Immunocore. G. Beasley: Financial Interests, Institutional, Research Funding: Replimune, Checkmate Pharmaceuticals, Philogen, Delcath Systems; Financial Interests, Personal, Advisory Board: BMS. R. Dummer: Financial Interests, Personal, Other, Consulting and/or advisory role: Novartis, Merck Sharp & Dohme (MSD), Bristol Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, MaviVAX SA, T3 Pharma, Pfizer, Simcere. A.M. Arance: Financial Interests, Personal, Speaker, Consultant, Advisor: Pierre Fabre, Novartis, Roche, BMS, MSD, Biontech; Financial Interests, Personal, Other, Travel, accommodations, expenses: BMS, MSD. J. John: Financial Interests, Personal, Full or part-time Employment: Delcath Systems. J.S. Zager: Financial Interests, Personal, Advisory Board: Delcath Systems; Financial Interests, Personal and Institutional, Principal Investigator: Delcath Systems; Financial Interests, Institutional, Research Grant: Delcath Systems. All other authors have declared no conflicts of interest.