Delcath Systems, Inc. · NASDAQ:DCTH
Delcath Systems — Technical Presentation (June 2010)
30 slides from Delcath Systems's technical presentation, Jun 5, 2010
Slide 1: Phase-III Trial of PHP-mel vs Standard of Care for Hepatic Metastases from Melanoma
A Phase-III Random Assignment Trial Comparing Percutaneous Hepatic Perfusion with Melphalan (PHP- mel) to Standard of Care for Patients with Hepatic Metastases from Metastatic Ocular or Cutaneous Melanoma. (LBA #8512) James F. Pingpank, Jr, FACS Associate Professor of Surgery, Division of Surgical O
Slide 2: Disclosures
Disclosures James F. Pingpank, Jr., MD Scientific Advisory Board (Delcath Systems, Inc; New York, NY) Research Support (Delcath Systems, Inc; New York, NY) Jonathan Zager, MD: Scientific Advisory Board (Delcath Systems, Inc; New York, NY) All participating institutions received research support from
Slide 3: Treatment of Patients with Hepatic Metastases from Ocular Melanoma
Treatment of Patients with Hepatic Metastases from Ocular Melanoma Incidence of ocular melanoma is 3,500-4,000/year – 50 to 60% of patients with ocular melanoma will recur – Liver is the sole or dominant site of disease in over 80% • 1,500 to 2,000/year • median survival ~ 2 to 7 months • 1-year sur
Slide 4: Rationale for Regional Therapy
Rationale for Regional Therapy Regional therapy allows dose escalation to the cancer-bearing region or organ of the body while minimizing systemic exposure and toxicity, via complete separation of the regional and systemic circulation Eliminates or significantly reduces systemic toxicity, and dose e
Slide 5: Schematic of IHP Circuit and Operative Dissection (290 procedures)
Schematic of IHP Circuit and Operative Dissection (290 procedures) Supra-Hepatic IVC Retro-Hepatic IVC Porta Hepatis Dissection
Slide 6: Isolated Hepatic Perfusion (Melphalan) - Ocular Melanoma
Isolated Hepatic Perfusion (Melphalan) -Ocular Melanoma- Patients: n=29 pts Overall Response Rate: 62% Median OS: 12.1 m Alexander HR: Clin Cancer Res 2003 15;9(17):6343-9.
Slide 7: Updated IHP Dissection and Circuit
Updated IHP Dissection and Circuit (Combined percutaneous and operative technique) Supra-Hepatic IVC Retro-Hepatic IVC Zeh HJ, Bartlett DL. Ann Surg Oncol 2009; 16:385-94. Porta Hepatis Dissection
Slide 8: Percutaneous Hepatic Perfusion
Percutaneous Hepatic Perfusion Melphalan Phase I MTD: 3.0 mg/kg (based upon IBW)
Slide 9: Phase I Trial Design
Phase I Trial Design 12 Patient “Feasibility” Dose Escalation Schedule Dose Level Melphalan (mg/kg) No. of Patients 1 2.0 12 2 2.5 3 3 3.0 7 4 3.5 6 Dose Limiting Toxicity 1. Grade IV neutropenia > 72 hours or with fevers 2. Grade III thrombocytopenia > 72 hours/bleeding 3. Grade IV hemoglobin > 7 d
Slide 10: Percutaneous Hepatic Perfusion
Percutaneous Hepatic Perfusion Systemic Sample Post-Filter Sample Pre-Filter Sample Infusion Sample Pingpank JF. J Clin Oncol 2005; 23, 3465-3474
Slide 11: Chemotherapy Levels During Therapy: IHP vs PHP
Chemotherapy Levels During Therapy IHP vs PHP Isolated Hepatic Perfusion Percutaneous Hepatic Hepatic Arterial Infusion Perfusion with Venous Filtration (Patient: William A, 3/4/03, 3 mg/kg, 178 mg) 20 Melphalan Concentration (g/ml) infusion Periphery Artery 1.5 mg/kg Pre-filter Post-filter 15 10 3
Slide 12: Phase I PHP: Metastatic Melanoma
Phase I PHP: Metastatic Melanoma Radiographic Treatment Response (n=16) Response n % Duration Overall 8 50 Complete 2 13 10, 15 Partial 6 37.5 2+,8, 8, 12, 15, 16 Stable Disease 4 25 7, 7, 8, 8+ Progressive Disease 4 25 Not Evaluable 2 13 (vascular anomaly) Follow-up Status DOD (Dead of disease) 16
Slide 13: Phase III Random-Assignment PHP vs. Best Available Care (FDA SPA)
Phase III Random-Assignment PHP vs. Best Available Care (FDA SPA) Accrual goal: 92 patients (Cross-over at Hepatic progression) 10 Institutions Melphalan dose: 3.0 mg/kg Stratification: Cutaneous vs. Ocular Primary endpoint: Hepatic PFS Secondary endpoints: 1. Response rates, DFS with best available
Slide 14: Phase III Random-Assignment PHP vs. Best Available Care
Phase III Random-Assignment PHP vs. Best Available Care 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 PHP: 7.73 months Best Alternative Care (Control): 4 months Staging Scans: Baseline, 6 weeks, 12 weeks, then
Slide 15: PHP Arm Treatment Schema
PHP Arm Treatment Schema On Study Evaluation/Randomization Post Treatment Follow-up 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 4-5
Slide 16: Randomization and Treatment Schema
Results: Randomization and Treatment Schema -93 Patients at 10 Institutions- H E P A PHP Arm T R Follow-up (n= 44) I A C N Melanoma D Metastatic P O Cross over to PHP R to Liver M (n=27, 55%) O (n = 93) I G Z R E E BAC Arm S Follow-up 1:1 (n = 49) S I Total Accrual: 93 patients O (PHP: 44, BAC: 49,
Slide 17: Patient Demographics
Results: Patient Demographics Baseline Characteristic Category PHP (N=44) BAC (N=49) P value* Age (years) Mean 54.8 54.8 0.9866 Male 23 (52.3%) 22 (44.9%) Gender 0.5362 Female 21 (47.7) 27 (55.1) White 44 (100.0) 48 (98) Race 1.0000 Non-White 0 (0.0) 1 (2.0) Missing 3 (6.8) 4 (8.2) ECOG 0 37 (84.1)
Slide 18: Patient Demographics - Prior Therapy
Results: Patient Demographics -Prior Therapy- Therapy PHP (N=44) BAC (N=49) All (N=93) P Value* Radiation 24 47 23 Therapy (49.0%) (50.5%) 0.8364 (52.3%) (primary tumor) 6 13 7 Chemotherapy (12.2%) (14.0%) 0.7664 (15.9%) 7 13 6 Immunotherapy (14.3%) (14.0%) 1.0000 (13.6%) 3 5 Image Directed 2 (6.1%)
Slide 19: Treatment Related Toxicities
Results: Treatment Related Toxicities (40 Patients, 116 Treatments) Treatment Related Toxicity, Grade 3-4 and Grade 5 (n=116 treatments) Hematologic Grade 3-4 (n,%) Grade 5 (n,%) Neutropenia 71 (61.2%) 2 (1.7%) Thrombocytopenia 86 (74.1%) Anemia 54 (46.6%) Hepatic Elevated AST 14 (12.1%) Elevated AL
Slide 20: Primary Endpoint - Hepatic Progression Free Survival (ITT)
Results: Primary Endpoint -Hepatic Progression Free Survival (ITT) - Hazard Ratio: 0.301 (CI: 0.183-0.497)
Slide 21: Secondary Endpoint - Overall Progression Free Survival (ITT)
Results: Secondary Endpoint -Overall Progression Free Survival (ITT)- Hazard Ratio: 0.404 (CI: 0.252-0.648)
Slide 22: Secondary Endpoint - Overall Survival (ITT)
Results: Secondary Endpoint -Overall Survival (ITT)- Hazard Ratio: 0.920 (CI: 0.524-1.615)
Slide 23: Secondary Endpoint - Overall Survival BAC Patients
Results: Secondary Endpoint -Overall Survival BAC Patients-
Slide 24: Analysis of Factors Associated with Survival
Results: Analysis of Factors Associated with Survival Variable Hazard Ratio Confidence Interval Melphalan 0.301 0.18 – 0.50 Gender 1.1 0.70 – 1.81 >65 years old 1.3 0.66 – 2.56 Ocular/Cutaneous 0.7 0.32 – 1.71 >1 year of disease 0.8 0.45 – 1.46 Melphalan, controlling 0.283 0.17 – 0.47 for all of the
Slide 25: Secondary Endpoint - Response (ITT)
Results: Secondary Endpoint -Response (ITT)- Best Alternative Care PHP All Crossover Non-Cross Overall Response: n (%) (N= 44) (n=49) (N= 27) (N= 22) CR 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) PR 15 (34.1) 1 (2.0) 6 (22.2) 1 (4.5) SD 23 (52.3) 13 (26.5) 11 (40.7) 6 (27.3) PD 2 (4.5) 31 (63.3) 1 (3.7) 12 (54
Slide 26: Secondary Endpoint - Response (ITT)
Results: Secondary Endpoint -Response (ITT)- Best Alternative Care PHP All Crossover Non-Cross Overall Response: n (%) (N= 44) (n=49) (N= 27) (N= 22) CR 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) PR 15 (34.1) 1 (2.0) 6 (22.2) 1 (4.5) SD 23 (52.3) 13 (26.5) 11 (40.7) 6 (27.3) PD 2 (4.5) 31 (63.3) 1 (3.7) 12 (54
Slide 27: Secondary Endpoint - Response (ITT)
Results: Secondary Endpoint -Response (ITT)- Best Alternative Care PHP All Crossover Non-Cross Overall Response: n (%) (N= 44) (n=49) (N= 27) (N= 22) CR 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) PR 15 (34.1) 1 (2.0) 6 (22.2) 1 (4.5) SD (median 259 days) 23 (52.3) 13 (26.5) 11 (40.7) 6 (27.3) PD 2 (4.5) 31 (63
Slide 28: Conclusions
Conclusions Increased drug delivery achieved through novel regional therapeutic approaches may increase efficacy of a given agent (vs. systemic administration) by overcoming a low therapeutic index. High-dose Melphalan, delivered via intra-arterial administration with subsequent hepatic venous hemof
Slide 29: Acknowledgements
Acknowledgements NCI (Bethesda, MD) Atlantic Health Care System Marybeth Hughes, MD, FACS (Morristown, NJ) Eric Whitman, MD Bradford J. Wood, MD Swedish Medical Center (Denver, CO) Maryann Toomey, RN Charles Nutting, DO University of Maryland Albany Medical Center (NY) H. Richard Alexander, MD, FACS
Slide 30: Phase-III Trial of PHP-mel vs Standard of Care for Hepatic Metastases from Melanoma
A Phase-III Random Assignment Trial Comparing Percutaneous Hepatic Perfusion with Melphalan (PHP- mel) to Standard of Care for Patients with Hepatic Metastases from Metastatic Ocular or Cutaneous Melanoma. (LBA #8512) James F. Pingpank, Jr, FACS Associate Professor of Surgery, Division of Surgical O