A Study of AGS-1C4D4 Given in Combination With Gemcitabine in Subjects With Metastatic Pancreatic Cancer

• Overall Survival (OS) [ Time Frame: Throughout treatment period and post-treatment every 2 months until death, or subject discontinues the study ] [ Designated as safety issue: No ]
• Progression free survival (PFS) [ Time Frame: Throughout treatment period or post-treatment every 2 months until disease progression or death, respectively, or subject discontinues the study ] [ Designated as safety issue: No ]
• Change in level of serum tumor marker CA 19-9 [ Time Frame: Week 1, Week 4, Week 7 and every 3 weeks during the extended treatment period ] [ Designated as safety issue: No ]
• Incidence of anti-AGS-1C4D4 antibody formation [ Time Frame: Week 1, Week 7 and every 8 weeks during the extended treatment period ] [ Designated as safety issue: No ]
• Objective Response Rate (Partial Response or better per RECIST criteria version 1.1 [ Time Frame: Week 8, and every 8 weeks during the extended treatment period ] [ Designated as safety issue: No ]
• Disease Control (Stable Disease or better per RECIST criteria) [ Time Frame: Week 8, and every 8 weeks during the extended treatment period ] [ Designated as safety issue: No ]

• Overall Survival (OS) [ Time Frame: Throughout treatment period and post-treatment every 2 months until death, or subject discontinues the study ] [ Designated as safety issue: No ]
• Progression free survival (PFS) [ Time Frame: Throughout treatment period or post-treatment every 2 months until disease progression or death, respectively, or subject discontinues the study ] [ Designated as safety issue: No ]
• Best tumor response (stable disease, or better per RECIST criteria) [ Time Frame: Week 8, and every 8 weeks during the extended treatment period ] [ Designated as safety issue: No ]
• Change in level of serum tumor marker CA 19-9 [ Time Frame: Week 1, Week 4, Week 7 and every 3 weeks during the extended treatment period ] [ Designated as safety issue: No ]
• Incidence of anti-AGS-1C4D4 antibody formation [ Time Frame: Week 1, Week 7 and every 8 weeks during the extended treatment period ] [ Designated as safety issue: No ]

A study to evaluate AGS-1C4D4 administered in combination with Gemcitabine chemotherapy in subjects with Metastatic Pancreatic Cancer.

A disease assessment will be performed at study week 8 (± 3 days) by the investigator. The assessment will be based both on changes in clinical symptoms, and radiographic images. Subjects without evidence of disease progression may continue to receive treatment based on their original treatment assignment until disease progression or intolerability. Disease assessments will be performed every 8 weeks during the extended period. A safety follow-up visit will occur 4 weeks after the last dose infusion of AGS-1C4D4 and/or gemcitabine.

Post-Treatment: Subjects terminating from protocol therapy for reasons unrelated to documented disease progression will be followed by telephone contact every 2 months until they begin a new anticancer therapy, their disease progresses, they die, become lost to follow-up or withdrawal consent for further follow-up, whichever of these events occurs first.

Overall survival: All subjects will be followed by telephone contact every 2 months until death, loss to follow-up, or withdrawal of consent, whichever of these events occurs first.

• Carcinoma, Pancreatic Ductal
• Pancreatic Cancer
• Pancreatic Disease

• Biological: AGS-1C4D4
  IV infusion
• Biological: Gemcitabine
  IV infusion

• Active Comparator: 1. Gemcitabine monotherapy
  Intervention: Biological: Gemcitabine
• Experimental: 2. Gemcitabine plus AGS-1C4D4
  Interventions:

  • Biological: AGS-1C4D4
  • Biological: Gemcitabine

Inclusion Criteria:

• Pathologically confirmed metastatic adenocarcinoma of the pancreas (AJCC Stage IV). Subjects with islet cell neoplasms are excluded
• Non-measurable or measurable disease based on the RECIST criteria
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Life expectancy of > 3 months

• Hematologic function, as follows:

  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  • Platelet count ≥ 100 x 109/L
  • Hemoglobin ≥ 9 g/dL (transfusion independent)

• Renal function, as follows:

  • Creatinine ≤ 2.0 mg/dL

• Hepatic function, as follows:

  • Aspartate aminotransferase (AST) ≤ 2.5 x ULN or ≤ 5 x ULN if known liver metastases.
  • Alanine aminotransferase (ALT) ≤ 2.5 x ULN or ≤ 5 x ULN if known liver metastases
  • Bilirubin ≤ 2 x ULN
• INR < 1.3 (or ≤ 3 if on warfarin for therapeutic anti-coagulation)

Exclusion Criteria:

• Prior systemic therapy for metastatic pancreatic cancer

  • Subjects who have received adjuvant treatment with gemcitabine and who had relapse metastatically are allowed
  • Subjects with advanced local disease who have received treatment with gemcitabine and in whom progression has been observed with the onset of metastases less than 6 months are excluded
• Chemotherapy and/or radiation within 4 weeks of study enrollment
• Prior monoclonal antibody therapy within 60 days of study enrollment
• Known brain or leptomeningeal disease

• History of other primary malignancy, unless:

  • Curatively resected non-melanomatous skin cancer
  • Other malignancy curatively treated with no known active disease present and no treatment administered for the last 3 years
• Active angina or Class III or IV Congestive Heart Failure (New York Heart Association CHF Functional Classification System)
• Use of any investigational product within 4 weeks of study enrollment
• Major surgery (that requires general anesthesia) within 4 weeks before study enrollment
• Women who are pregnant (confirmed by positive pregnancy test) or lactating
• Man or woman of childbearing potential not consenting to use adequate contraceptive precautions during the course of the study and for 4 weeks after the last AGS-1C4D4 and/or gemcitabine infusion administration
• Subject known to be human immunodeficiency, hepatitis B or hepatitis C virus positive
• Active serious infection not controlled with antibiotics