Details

Details

Title A Phase 1b/2 Study of OMP-59R5 in Combination with Nab-Paclitaxel and Gemcitabine in Subjects with Previously Untreated Stage IV Pancreatic Cancer ALPINE: Antibody therapy in first-Line Pancreatic cancer Investigating anti-Notch Efficacy and safety

IRB OMP1213

CC 14-124

Hospital Main Campus

Stage Stage 4

Phase Phase 1, Phase 2

Disease Pancreas

Drug Gemcitabine , Nab-Paclitaxel, OMP-59R5

Description

Description

Primary Objectives:
  • To determine the maximum tolerated dose (MTD) of tarextumab when administered every other week (Days 1 and 15) in combination with nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 on Days 1, 8 and 15 of every 28-day cycle in subjects with previously untreated stage IV pancreatic cancer (Phase 1b portion)
  • To determine the clinical benefit, as measured by overall survival (OS) of the addition of tarextumab to nabpaclitaxel and gemcitabine (Nab-P+Gem) in all subjects who are receiving first-line therapy for stage IV pancreatic cancer (Phase 2 portion)
  • To determine the clinical benefit, as measured by OS of the addition of tarextumab to Nab-P+Gem across the four subject subsets: subjects with Notch3 ≥25th percentile, subjects with Notch3 ≥50th percentile, subjects with Notch3 ≥75th percentile and all subjects receiving first-line therapy for stage IV pancreatic cancer
Secondary Objectives:
  • To determine the pharmacokinetics of tarextumab in combination with Nab-P+Gem in subjects with previously untreated stage IV pancreatic cancer (Phase 1b and 2 portions)
  • To determine the immunogenicity of tarextumab in combination with Nab-P+Gem in subjects with previously untreated stage IV pancreatic cancer (Phase 1b and 2 portions)
  • To estimate the clinical benefit, as measured by Progression free survival (PFS), 12 months OS rate and overall response rate (ORR) of the addition of tarextumab to Nab-P+Gem in all subjects who are receiving first-line therapy for stage IV pancreatic cancer (Phase 2 portion)
  • To determine the clinical benefit, as measured by PFS of the addition of tarextumab to Nab-P+Gem across the four subject subsets: subjects with Notch3 ≥25th percentile, subjects with Notch3 ≥50th percentile, subjects with Notch3 ≥75th percentile and all subjects receiving first-line therapy for stage IV pancreatic cancer (Phase 2 portion)
  • To determine the safety and tolerability of tarextumab in combination with Nab-P+Gem in subjects with stage IV pancreatic cancer (Phase 1b and 2 portions in subjects receiving tarextumab with Nab-P+Gem)
Exploratory Objectives:
  • To assess exploratory pharmacodynamic biomarkers, including Notch pathway related genes and proteins and circulating tumor cells following tarextumab treatment
  • To correlate the clinical benefit, as measured by PFS of the addition of tarextumab to Nab-P+Gem in subjects receiving first-line therapy for stage IV pancreatic cancer with Notch3 high expression level (Phase 1b)
  • To estimate the clinical benefit, as measured by response of CA19-9 (≥50% reduction from the baseline) of the addition of tarextumab to Nab-P+Gem in all subjects who are receiving first-line therapy for stage IV pancreatic cancer (Phase 2 portion)
  • To evaluate the dependence of the clinical benefit, as measured by response of CA19-9 (≥50% reduction from the baseline) of the addition of tarextumab to Nab-P+Gem in subjects who are receiving first-line therapy for stage IV pancreatic cancer on the level of Notch3 expression level (Phase 2 portion)
Inclusion Criteria

Inclusion Criteria

  1. 18 years of age or older
  2. Histologically or cytologically documented stage IV adenocarcinoma of the pancreas.
  3. Performance Status (ECOG) 0 or 1.
  4. FFPE tumor tissue from metastatic site(s), either fresh core needle biopsied (two cores preferred wheneverpossible), or archived available for Notch3 analysis.
  5. Adequate organ function:
    • Adequate hematologic function (absolute neutrophil count [ANC] ≥1.5 x 109/L; hemoglobin ≥9 g/dL, platelets ≥100 x 109/L) - have not received hematopoietic growth factors, transfusion of blood and blood products ≥ 1 week prior to meeting the eligibility criteria.
    • Adequate renal function (serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥60 mL/min using Cockcroft and Gault formula).
    • Adequate hepatic function (bilirubin ≤ 1.5 x upper limit of normal [ULN], alanine aminotransferase [ALT] ≤ 3 x ULN, aspartate aminotransferase [AST] ≤ 3 x ULN).
    • Prothrombin Time (PT)/International Normalized Ration (INR) ≤1.5 x ULN, activated partial thromboplastin time (aPTT) ≤1.5 x ULN.
  6. Written consent on an IRB/IEC-approved Informed Consent Form prior to any study-specific evaluation.
  7. For women of child-bearing potential, negative serum pregnancy test at screening and use of physicianapproved method of birth control from 30 days prior to the first study drug administration to 30 days following the last study drug administration.
  8. Male subjects must be surgically sterile or must agree to use physician-approved contraception from 30 days prior to the first study drug administration to 30 days following the last study drug administration.
    9. Additionally, for individuals eligible to participate in Phase 2 portion of the study:
  9. Subject must have evidence of measurable disease per RECIST 1.1 criteria.
Exclusion Criteria

Exclusion Criteria

  1. Neuroendocrine tumors (i.e., carcinoid, islet cell cancer) of the pancreas.
  2. Known brain metastases.
  3. Prior therapy, including systemic therapy, surgical resection or radiation for the treatment of newly diagnosed stage IV pancreatic cancer.
  4. Presence of uncontrolled Grade ≥1 diarrhea.
  5. Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, uncontrolled intercurrent illness including active infection, arterial thrombosis, symptomatic pulmonary embolism).
  6. Any disorder that would significantly compromise protocol compliance.
  7. A history of malignancy with the exception of:
    • Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer
      • .
    • Superficial bladder cancer
    • Adequately treated stage I cancer from which the subject is currently in remission, or
    • Any other cancer from which the subject has been disease-free for ≥ 3 years
  8. Known human immunodeficiency virus (HIV) infection.
  9. Females who are pregnant or breastfeeding.
  10. Concurrent use of therapeutic warfarin.
  11. Major surgery <4 weeks prior to the first study drug administration.