Delcath Systems, Inc. · NASDAQ:DCTH
Delcath Systems — Technical Presentation (2011)
19 slides from Delcath Systems's technical presentation, 2011
Slide 1: Percutaneous Hepatic Perfusion vs. Best Alternative Care for Melanoma Liver Metastases
#<?> Percutaneous Hepatic Perfusion vs. Best Alternative Care for Patients with Melanoma Liver Metastases: Efficacy Update of the Phase 3 Trial (NCT00324727) J. Pingpank University of Pittsburgh Cancer Institute, Surgical Oncology, Hillman Cancer Center, Pittsburgh, PA 15232, USA
Slide 2: Background
Background There is no standard of care for liver-dominant metastatic melanoma Regional therapies provide a way of delivering intensified treatment to the whole organ while limiting unwanted systemic toxicity – chemosaturation with percutaneous hepatic perfusion (CS- PHP) can deliver repeated hi
Slide 3: Chemosaturation-PHP
Chemosaturation-PHP CS-PHP isolates the liver from the systemic circulation using a purpose-designed system of catheters and filters (Delcath Systems Inc, New York, NY) It allows direct infusion of high-dose chemotherapy into the liver via the hepatic artery, delivering a saturating dose of chem
Slide 4: Chemosaturation-PHP procedure
Chemosaturation-PHP procedure 4
Slide 5: Study design and endpoints
Study design and endpoints Randomized, open-label, multicenter phase 3 study Primary study endpoint: – hepatic progression-free survival (hPFS) Secondary endpoints included: – hepatic objective response rate – overall survival – safety 5
Slide 6: Patient population
Patient population Proven ocular or cutaneous metastatic melanoma predominantly in the liver parenchyma Limited extrahepatic disease Adequate hepatic function: – total serum bilirubin <3.0 mg/dL – prothrombin time within 2 seconds of ULN – liver function tests ≤10 x ULN No portal hypertensio
Slide 7: Study treatments
Study treatments CS-PHP with melphalan – melphalan 3.0 mg/kg as a 30-minute infusion via CS-PHP – an additional 30 minutes of extracorporeal filtration after each infusion was performed – CS-PHP given while patients under general anesthesia – up to six treatments repeated every 4–8 weeks Best al
Slide 8: Patient flowchart
Patient flowchart Ocular or cutaneous melanoma with liver metastases (N=93) RANDOMIZATION CS-PHP melphalan (N=44) BAC (N=49) Did not receive treatment Active treatment (n=40) (n=4) Supportive care (n=9) H E PAT I C D I S E AS E P R O G R E S S I O N Crossover Follow-up Follow-up to CS-PHP (N=44) (N=
Slide 9: Results
Results Patient characteristics Between February 2006 and October 2009, 93 patients were enrolled at 12 US centers – most (88%) had ocular melanoma – metastases were generally confined to the liver (71%) 9
Slide 10: Baseline characteristics (ITT population)
Baseline characteristics (ITT population) CS-PHP BAC Characteristic (N=44) (N=49) P value Median age, years 55 56 NS Primary tumor site, % Ocular 89 88 NS Cutaneous 11 12 NS Hepatic tumor burden, % <50% 77 78 NS ≥50% 18 22 NS Unknown 5 0 Extrahepatic sites, % 28 33 NS Previous treatment, % Radiation
Slide 11: Treatment exposure
Treatment exposure Median of 3 (range, 1–6) CS-PHP treatments Median melphalan dose 187 mg (range, 85-220 mg) BAC constituted active treatment (n=40) or supportive care (n=9) Active BAC treatments: – single-agent chemotherapy (n=25, mostly temozolomide) – chemoembolization (n=5) – intrahepat
Slide 12: Efficacy (ITT population)
Efficacy (ITT population) CS-PHP BAC Hazard ratio Endpoint (N=44) (N=49) (95% CI) P value hPFS (investigator) Median, months 8.0 1.6 0.35 (0.23–0.54) <0.0001 hPFS (IRC) Median, months 7.0 2.3 0.61 (0.40–0.94) 0.0236 Overall survival Median, months 9.8 9.9 1.08 (0.69–1.68) 0.740 Hepatic response rate
Slide 13: Hepatic progression-free survival
Hepatic progression-free survival Investigator-assessed hPFS Intent-to-treat population 13
Slide 14: Hepatic progression-free survival
Hepatic progression-free survival IRC-assessed hPFS Intent-to-treat population 14
Slide 15: Overall survival: exploratory analysis
Overall survival: exploratory analysis BAC alone (n=21) vs. BAC with crossover to CS-PHP melphalan (n=28) Median 15.3 months Median 4.1 months 15
Slide 16: Safety
Safety The most common grade 3/4 adverse events associated with CS-PHP melphalan were thrombocytopenia, anemia and hypoalbuminemia Reductions in neutrophil and white blood cell counts during the post- procedural period were also common – febrile neutropenia documented in 6 (15%) patients Hepat
Slide 17: Most common adverse events (n=40)
Most common adverse events (n=40) Grade 3/4 events No. of patients (%) Peri-procedural* Cycle toxicity† Neutrophil count decreased <?> (<?>) 37 (93) Platelet count decreased 29 (73) 33 (83) Hemoglobin decreased 22 (55) 22 (55) White blood cell count decreased <?> (<?>) 23 (58) Blood albumin decrease
Slide 18: Adverse events of special interest (n=40)
Adverse events of special interest (n=40) Grade 3/4 events No. of patients (%) Peri-procedural* Cycle toxicity† Any bleeding event 20 (50) 22 (55) Any gastrointestinal event 0 (0) 3 (8) Abdominal pain 0 (0) 2 (5) Nausea 0 (0) 1 (3) Edema <?> (<?>) 2 (5) Febrile neutropenia 0 (0) 6 (15) Hypersensitiv
Slide 19: Conclusions
Conclusions Melphalan delivered via CS-PHP significantly prolonged hPFS compared with BAC in patients with liver-dominant metastatic melanoma, thereby meeting the study primary objective – investigator analysis of hPFS was confirmed by IRC analysis – CS-PHP melphalan also significantly improved he