Delcath Systems, Inc. · NASDAQ:DCTH
Delcath Systems — Technical Presentation (2012)
24 slides from Delcath Systems's technical presentation, 2012
Slide 1: Chemosaturation Therapy: Percutaneous Hepatic Perfusion vs Best Available Care
Chemosaturation Therapy Percutaneous Hepatic Perfusion (PHP) Compared with Best Available Care (BAC) For Un-resectable Metastatic Melanoma in the Liver PH-III Randomized US Multi-Center Trial Investigators APCCVIR 2012; Abstract #00136
Slide 2: Phase 3 Study Investigators
PHASE 3 STUDY INVESTIGATORS Marybeth Hughes, National Cancer Institute, Bethesda, MD H. Richard Alexander, U. of Maryland School of Medicine, Baltimore, MD Mark Faries, John Wayne Cancer Institute, Santa Monica, CA James F. Pingpank, U. of Pittsburgh, Hillman Cancer Center, Pittsburgh, PA Jonathan S
Slide 3: Chemosaturation Therapy (CS-PHP)
CHEMOSATURATION Therapy (CS- PHP) Isolation Saturatio Filtratio n n A PERCUTANEOUS ALTERNATIVE to IHP
Slide 4: Filtration Procedure
Filtration Procedure Chemo Filtration Chemo Isolation & Circuit Delivery Circuit
Slide 5: Melphalan
MELPHALAN A bi-functional alkylating agent (nitrogen mustard) Not cell-cycle specific – binds DNA strands Cytotoxic effects are related to concentration and duration of exposure Non-toxic to normal hepatocytes Track record with surgical IHP
Slide 6: Drug Levels During Therapy
Drug Levels During Therapy Pingpank JF, et al. J Clin Oncol
Slide 7: Phase III: CS-PHP vs. BAC Study Design Elements
PHASE III: CS-PHP VS. BAC STUDY DESIGN ELEMENTS • Conducted under Special Protocol Assessment (SPA) of US-FDA: • Primary Endpoint: Hepatic Progression Free Survival (hPFS) • Cross-Over: of BAC patients at hepatic progression • Stratification: Cutaneous vs. Ocular • Lead Center: National Cancer Insti
Slide 8: Phase III: Statistical Analysis Plan
PHASE III: PHP-CS VS. BAC STATISTICAL ANALYIS PLAN • Sample size: 46 patients per arm • Alpha: p≤0.05 (2-sided ) • Power: 80% to detect a difference of 4 months Hepatic PFS • Expected Hepatic PFS (used for sample size determination) • PHP (Treatment): 7.73 months • Best Alternative Care (Control): 4
Slide 9: PHP-CS Arm Treatment Schema
PHP-CS Arm Treatment Schema On Study Post Treatment Follow-up Evaluation/Randomization Interval Evaluation* (Baseline, 6-weeks, 12 weeks, 20 weeks, 28 weeks, 36 weeks) Treatments 1 through 6 - Melphalan - Angiogram (Celiac, SMA) - GDA assessment (Treatment #1) 4-5 Weeks 4-5 Weeks 4-5 Weeks 4-5 Weeks
Slide 10: Phase III Preliminary Results
PHASE III PRELIMINARY RESULTS*
Slide 11: Randomization and Treatment Schematic
Randomization and Treatment SchematicH Total Accrual: 93 patients (PHP: 44; BAC: 49, Crossover: 28) E P A T R PHP ARM I FOLLOW-UP A (N= 44) C N Cross over to D P CHEMOSATU MELANOM O R RATIOIN PHP A M O (n=28, 57%) METASTA I G TIC Z R TO LIVER E E (N = 93) BAC S 1: ARM S FOLLOW-UP 1 I (N = 49) O Scan
Slide 12: Patient Demographics
Patient Demographics Baseline Category PHP BAC P value* Characterist N=44 (%) N=49 (%) ic Age (years) Mean 55 55 NS Gender Male 23 (52) 22 (45) NS Female 21 (48) 27 (55) Race White 44 (100) 48 (98) NS Non-White 0 (0) 1 (2) ECOG Missing 3 (7) 4 (8) NS 0 37 (84) 42 (86) 1 4 (9) 3 (6) Primary Ocular 39
Slide 13: Therapy Prior to Randomization
Therapy Prior to Randomization Therapy CS-PHP BAC All P Value* N=44 (%) N=49 (%) N=93 (%) Radiation 23 24 47 NS (primary (52) (49) (51) tumor) Chemotherapy 7 6 13 NS (16) (12) (14) Immunotherap 6 7 13 NS y (14) (14) (14) Image 2 3 5 NS Directed Local (5) (6) (5) Therapy Unknown 0 1 1 NS (0) (2) (1)
Slide 14: PH-III Randomized US Trial Primary End Point
PH-III Randomized US Trial Primary End Point
Slide 15: Hepatic Progression-free Survival (ITT)
Hepatic Progression-free Survival (ITT) Survival probability 1.0 CS-PHP BAC 0.8 Hazard Ratio: 0.6 0.35 (CI: p<0.0001 0.23-0.54) 8.0 1.6 0.4 0.2 0.0 0 5 10 15 20 25 30 35 Months 3/31/11 Pingpank JF, et al. ECCO-ESMO 2011
Slide 16: PH-III Randomized US Trial Secondary End Points
PH-III Randomized US Trial Secondary End Points
Slide 17: Overall Progression-free Survival (ITT)
Overall Progression-free Survival (ITT) Survival probability 1.0 CS-PHP BAC 0.8 Hazard Ratio: 0.6 0.36 (CI: p<0.0001 0.23-0.57) 6.7 1.6 0.4 0.2 0.0 0 5 10 15 20 25 30 35 Months Pingpank JF, et al. ECCO-ESMO 2011
Slide 18: Overall Survival (ITT)
Overall Survival (ITT) Survival probability 1.0 CS-PHP BAC 0.8 Hazard Ratio: 0.6 1.08 (CI: p=0.74 0.69-1.68) 9.8 9.9 0.4 55% crossover 0.2 0.0 0 5 10 15 20 25 30 35 40 45 50 55 Months Pingpank JF, et al. ECCO-ESMO 2011
Slide 19: Factors Associated with Survival
Factors Associated with Survival Survival was Highly Associated with Use of Melphalan with CS-PHP Pingpank JF, et al. ASCO 2010
Slide 20: Secondary Endpoint: Hepatic Response Rate
Secondary Endpoint: Hepatic Response Rate Disease Control Rate (CR+PR+SD): CS-PHP: 39 (88.6%) versus BAC: 14 (30.6%) Pingpank JF, et al. ECCO-ESMO 2011
Slide 21: Treatment Related Toxicities of CS-PHP
Phase III: Treatment Related Toxicities of CS-PHP Treatment Related Toxicity*, Grade 3-4 and Grade 5, (116 treatments) Hematologic Grade 3-4, n(%) Grade 5, n(%) Neutropenia 71 (61) 1 (<1) Thrombocytopenia 86 (74) 1 (<1) Anemia 54 (47) Hepatic Elevated AST 14 (12) Elevated ALT 6 (5) Hyperbilirubinemi
Slide 22: Phase III Melanoma Study: Safety
PHASE 3 MELANOMA STUDY: SAFETY Most common grade 3/4 AEs (peri-procedure) o thrombocytopenia, anemia and hypoalbuminemia Melphalan-related neutropenia, leukopenia (in cycle) o febrile neutropenia in 6 (15%) patients Transient peri-procedural transaminitis and hyper-bilirubinemia (10 - 30%) N
Slide 23: Conclusions
Conclusions • Significant improvement in hPFS (INV) – 6.4 months at median: HR 0.35 (p < 0.0001) • Consistent with IRC (incl. secondary endpoints) • No difference in mOS due to cross-over (ITT) – 55% crossover from BAC to PHP-melphalan • Transient LFT elevations – no Rx required • Expected & managea
Slide 24: Thank you
= f°) >) ~~ = © — -