Delcath Systems, Inc. · NASDAQ:DCTH
Delcath Systems — Technical Presentation (2012)
26 slides from Delcath Systems's technical presentation, 2012
Slide 1: Chemosaturation Therapy with Percutaneous Hepatic Perfusions of Melphalan Phase 3 Study
Chemosaturation Therapy with Percutaneous Hepatic Perfusions of Melphalan Versus Standard of Care in Patients with Hepatic Metastases from Melanoma: A Randomized Multicenter Phase 3 Study C.W. Nutting & J.S. Zager on behalf of the DCTH P3 Investigators Swedish Medical Center, Englewood, CO, USA H. L
Slide 2: Study Investigators
Study Investigators Marybeth Hughes, National Cancer Institute, Bethesda, MD H. Richard Alexander, University of Maryland School of Medicine, Baltimore, MD Mark Faries, John Wayne Cancer Institute, Santa Monica, CA Gary Siskin, Albany Medical Center Hospital, Albany NY Sanjiv Agarwala, St Luke’s Hos
Slide 3: Disclosures
Disclosures • Nutting: PI • Zager: PI 2
Slide 4: Background
Background There is no standard of care for liver-dominant metastatic melanoma; if untreated, the prognosis is dismal Recently introduced drugs are limited by tolerability, long induction periods, and applicability Regional therapies deliver high chemotherapy doses to the whole organ while lim
Slide 5: Chemosaturation-PHP
Chemosaturation-PHP* Percutaneously isolates the liver from the systemic circulation using a system of special catheters Directly infuses high-dose chemotherapy into the liver via the hepatic artery, allowing saturation of the entire organ Saturation of the entire organ exposes both visible an
Slide 6: Chemotherapy Levels During Therapy
Chemotherapy Levels During Therapy Chemosaturation with PHP Hepatic Arterial Infusion with Venous Filtration Percutaneous Hepatic (Patient: William A, 3/4/03, Perfusion 3 mg/kg, 178 mg) 20 Melphalan Concentration ( g/ml) infusion Periphery Artery Pre-filter Post-filter 15 3.0 mg/kg 10 5 0 0 10 20 3
Slide 7: Melphalan Dosing Levels
Melphalan Dosing Levels Multiple Myeloma (label) 0.25 mg/kg1 Chemoembolization 0.62 mg/kg2 Surgical Isolated Hepatic Perfusion 1.5 mg/kg3 Percutaneous Hepatic Perfusion (PHP™) 3.0 mg/kg Myeloablation 2.5-3.5 mg/kg • Drug dosing 10x higher than FDA approved dose via traditional chemotherapy • Dose de
Slide 8: Angiographic considerations
Angiographic considerations 7
Slide 9: Patient population
Patient population Proven ocular or cutaneous metastatic melanoma predominantly in the liver parenchyma Limited extra-hepatic disease Adequate liver function – Total serum bilirubin <3.0 mg/dL – Prothrombin time within 2 seconds of ULN – Liver function tests ≤10 x ULN No portal hypertension
Slide 10: Study treatments
Study treatments CS-PHP with melphalan – 3.0 mg/kg as a 30-minute intra-arterial infusion – An additional 30 minutes of extracorporeal filtration at end of infusion (washout) – Under general anesthesia – Allowed up to 6 treatments, repeated every 4–8 weeks Best alternative care (BAC) – Investiga
Slide 11: Study design and endpoints
Study design and endpoints Randomized, open-label, multicenter phase 3 study Study endpoints – Primary • hepatic progression-free survival (hPFS) (RECIST) • defined as time from randomization to hepatic disease progression or death – Secondary • hepatic objective response rate • overall survival
Slide 12: Efficacy analysis
Efficacy analysis Primary analysis – Conducted after 73 hepatic progression events (per protocol) – Performed April 30 20101 Survival update – Updated findings as of 31 March 2011 presented Exploratory post-hoc analysis – BAC patients who crossed over to CS-PHP vs BAC only 1. Pingpank J, et al
Slide 13: 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 (n=4) Active treatment (n=39) Supportive care (n=10) HEPATIC DISEASE PROGRESSION Crossover Follow-up Follow-up to CS-PHP (N=44) (N=21) (N=28) 12
Slide 14: Results
Results Patient characteristics Between February 2006 and October 2009, 93 patients were enrolled at 10 US centers – Most (88%) had ocular melanoma – Metastases were generally confined to the liver (71%) 13
Slide 15: Baseline characteristics (ITT population)
Baseline characteristics (ITT population) CS-PHP BAC Characteristic (N=44) (N=49) Median age, years 55 56 Primary tumor site, % Ocular 86 90 Cutaneous 11 10 Unknown 2 0 Hepatic tumor burden, % <50% 82 80 ≥50% 18 20 Extrahepatic sites, % 28 33 Previous treatment, % Radiation therapy 52 53 Surgery/pro
Slide 16: Baseline characteristics (BAC group, n=49)
Baseline characteristics (BAC group, n=49) Crossover to CS-PHP Follow-up Characteristic (N=28) (N=21) Median age, years 56 57 Primary tumor site, % Ocular 82 95 Cutaneous 18 5 Hepatic tumor burden, % <50% 86 67 ≥50% 14 33 Extrahepatic sites, % 36 28 Previous treatment, % Radiation therapy 54 52 Surg
Slide 17: 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=39) or supportive care/watchful waiting (n=10) Active BAC treatments – Temozolomide (n=20) – Chemoembolization (n=10) – Yttrium microspheres (n=3)
Slide 18: Phase III PHP results
Phase III PHP results Baseline (7-24-2006) Crossover (3-13-2007) Post treatment (4-11-2008) 17
Slide 19: Efficacy (randomized CS-PHP vs BAC)
Efficacy (patients randomized to CS-PHP vs randomized to BAC) CS-PHP BAC HR Endpoint (N=44) (N=49) (95% CI) P value 0.35 Median hPFS, months 8.0 1.6 p<0.0001 (0.23–0.54) 1.08 Median OS, months 9.8 9.9 p=0.7403 (0.69–1.68) ORR, % 32 2 – p=0.0001 ITT population Data as of 31 March 2011 18
Slide 20: Hepatic progression-free survival
Hepatic progression-free survival 1.0 6.4 Investigator-assessed hPFS BAC PHP 0.9 0.8 Proportion of patients surviving 0.7 0.6 0.5 8.0 HR=0.35 1.6 (95% CI 0.23–0.54) 0.4 p<0.0001 0.3 0.2 0.1 0.0 0 4 8 12 16 20 24 28 32 36 40 44 48 Time to hepatic progression (months) Intent-to-treat population 19
Slide 21: Efficacy (CS-PHP and by BAC subset)
Efficacy (CS-PHP and by BAC subset) CS-PHP BAC-to-PHP randomized BAC only crossover Endpoint (N=44) (N=21) (n=28) Median hPFS, months 8.0 1.6 8.8 HR (crossover vs BAC-only) 0.32 Median overall survival, months 9.8 4.1 15.3 HR (crossover vs BAC-only) 0.33 Still alive as of 31 March 2011 4 3* 7 Follow
Slide 22: Exploratory cross-over analysis: OS
Exploratory cross-over analysis: OS 1.0 11.2 BAC only BAC cross 0.9 0.8 Proportion of patients surviving 0.7 0.6 15.3 HR=0.33 0.5 p=0.0005 4.1 0.4 0.3 0.2 0.1 0.0 0 5 10 15 20 25 30 35 40 45 50 55 Time (months) Intent-to-treat population 21
Slide 23: Most common peri-procedural grade 3/4 AEs
Most common peri-procedural* grade 3/4 AEs (n=40) No. of pts % Platelet count decreased 29 73 Hemoglobin decreased 22 55 Blood albumin decreased 15 38 AST increased 12 30 aPTT prolonged 12 30 Blood calcium decreased 8 20 ALT increased 4 10 Blood bilirubin increased 4 10 *Day of treatment through to
Slide 24: Most common in-cycle grade 3/4 AEs
Most common in-cycle* grade 3/4 AEs (n=40) No. of pts % Neutrophil count decreased 37 93 Platelet count decreased 33 83 White blood cell count decreased 23 58 Hemoglobin decreased 22 55 Blood bilirubin increased 7 18 Febrile neutropenia 6 15 AST increased 5 13 Blood alkaline phosphatase 5 13 increas
Slide 25: Safety of CS-PHP melphalan
Safety of CS-PHP melphalan Most common grade 3/4 AEs were thrombocytopenia and anemia Low neutrophils, common during in-cycle period – febrile neutropenia in 6 patients (15%) Hepatic laboratory abnormalities in 10 to 30% of patients – Transient peri-procedural transaminitis – Hyperbilirubinemi
Slide 26: Conclusions
Conclusions CS-PHP significantly prolonged hPFS compared with BAC in patients with liver-dominant metastatic melanoma Study primary objective met – Investigator analysis confirmed by IRC and secondary endpoints CS-PHP significantly improved hepatic response rate Overall survival similar in b