The Current Prostate Cancer Landscape

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Marlene Hodge
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1 A Phase 1-2 Dose-Escalation and Safety Study of ADXS-PSA Alone and of ADXS-PSA in Combination with KEYTRUDA (MK-3475) in Patients with Previously Treated Metastatic Castration-Resistant Prostate Cancer (mcrpc) Dr. Naomi B. Haas, MD Associate Professor of Medicine Director of the Prostate and Kidney Cancer Programs University of Pennsylvania, Abramson Cancer Center 94

2 The Current Prostate Cancer Landscape Adjuvant/ Neoadjuvant Rising PSA Only Rising PSA and metastatic disease (noncastrate) Progression after ADT (castrate) Progression after Docetaxel ADT ADT Sipuleucel-T Cabazetaxel Docetaxel Clinical trials ADT + Docetaxel Ketoconazole Mitoxantrone and Prednisone ADT +RT Abiraterone Abiraterone Docetaxel Enzalutamide Enzalutamide Radium

3 Immunotherapy Characteristics Which Make Prostate Cancer Attractive Many tumor-associated but prostate tissue/cancer-specific antigens -PSA, prostatic acid phosphatase (PAP), and prostate-specific membrane antigen (PSMA) Elimination of all prostate cells would not interfere significantly with major organ function or general quality of life (post-castration) and any potential autoimmunity to prostate cells generated from immunotherapy would not impact patient safety. Prostate cancer is an immunologically and visible disease. Spontaneous autoantibodies, as shown by phage protein microarrays Initiation of chemical castration may result in lymphocyte infiltration into prostate tissue. Sipuleucel-T, an immunotherapy directed against PSMA improved the survival of men with prostate cancer (an improvement in median OS of 4.1 months when compared with placebo ) Prostate cancer tends to be a slow-growing disease, a relative benefit to immunotherapy. 96

4 Rationale for Combining ADXS-PSA with KEYTRUDA (MK 3475) Since in vitro studies suggested that addition of a monoclonal antibody against PD-1 was synergistic with ADXS-PSA in animal models and functioned to increase the number of tumor antigenspecific CD8+ T-cells, there is good rationale to combine these agents in the treatment of mcrpc. KEYTRUDA is a registered trademark of Merck & Co. 97

5 ADXS-PSA + KEYTRUDA (MK 3475) Phase 1/2 98

6 Objectives Primary Part A: to evaluate safety and tolerability of ADXS-PSA monotherapy and select the recommended Phase 2 dose (RP2D) in subjects with mcrpc Hypothesis: ADXS-PSA monotherapy has acceptable safety and tolerability in subjects with mcrpc Part B: to evaluate safety and tolerability of ADXS-PSA in combination with KEYTRUDA (MK 3475) and to establish the RP2D for this combination in subjects with mcrpc Hypothesis: ADXS-PSA + KEYTRUDA (MK 3475) combination therapy has acceptable safety and tolerability in subjects with mcrpc 99

7 Other Objectives Secondary Objective: to evaluate anti-tumor activity and progression free survival (PFS) signal of ADXS-PSA monotherapy and ADXS-PSA + KEYTRUDA (MK 3475) combination therapy using immune-related Response Evaluation Criteria in Solid Tumors (irrecist) and Prostate Cancer Working Group 2 (PCWG2) criteria to inform design of a subsequent randomized Phase 2 trial Exploratory Objective: to determine effects on serum prostate specific antigen (PSA) and peripheral immunologic measures of ADXS-PSA monotherapy and ADXS-PSA + KEYTRUDA (MK 3475) combination therapy Objective: to evaluate tissue samples for the evaluation of mechanism of action or predictive biomarkers 100

8 Eligibility Males 18 years old with histologically confirmed progressive mcrpc Patients must have at least 1 target lesion as defined by RECIST 1.1 No more than 3 prior systemic treatment regimens in the metastatic setting Adequate organ function 101

SESSIONE PLATINUM SERIES (Best Papers Poster o Abstract on Prostate Cancer) In Oncologia

SESSIONE PLATINUM SERIES (Best Papers Poster o Abstract on Prostate Cancer) In Oncologia Divisione di Oncologia Medica Unità Tumori Genitourinari SESSIONE PLATINUM SERIES (Best Papers Poster o Abstract