A Phase 1b/2 Study of OMP-59R5 (Tarextumab) in Combination With Nab-Paclitaxel and Gemcitabine in Subjects With Previously Untreated Stage IV Pancreatic Cancer

Study Overview
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Brief Summary
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The study consists of a Phase1b lead-in portion to determine the maximum tolerated dose (MTD) of OMP-59R5 in combination with nab-paclitaxel and gemcitabine followed by a Phase 2, multicenter, randomized, placebo-controlled portion to evaluate the efficacy and safety of OMP-59R5 in combination with nab-paclitaxel and gemcitabine in subjects with previously untreated stage IV pancreatic cancer.

Official Title
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A Phase 1b/2 Study of OMP-59R5 in Combination With Nab-Paclitaxel and Gemcitabine in Subjects With Previously Untreated Stage IV Pancreatic Cancer

Conditions
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Stage IV Pancreatic Cancer

Intervention / Treatment
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* Drug: OMP-59R5
* Drug: Gemcitabine
* Drug: Placebo
* Drug: Nab-Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet all of the following major inclusion criteria to be eligible for the study: 18 years of age or older Histologically or cytologically documented stage IV ductal adenocarcinoma of the pancreas. Performance Status (ECOG) 0 or 1 FFPE tumor tissue from metastatic site(s Adequate organ function Written consent on an IRB/IEC-approved Informed Consent Form prior to any study-specific evaluation. For women of child-bearing potential, negative serum pregnancy test at screening and use of physician-approved method of birth control from 30 days prior to the first study drug administration to 30 days following the last study drug administration. 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. Exclusion Criteria: Subjects who meet any of the following major exclusion criteria will not be eligible for participation in the study: Neuroendocrine tumors (i.e., carcinoid, islet cell cancer) of the pancreas. Known brain metastases. Prior therapy, including systemic therapy, surgical resection or radiation for newly diagnosed stage IV pancreatic cancer. 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). Any disorder that would significantly compromise protocol compliance. Prior non-pancreatic malignancy treated with chemotherapy. Prior malignancies treated with surgery and/or radiotherapy alone must be in remission ≥3 years. The following prior malignancies are allowable irrespective of when they occurred: in situ carcinoma of the cervix, in situ ductal breast cancer, low-grade local bladder cancer, and nonmelanotic skin cancer. Known human immunodeficiency virus (HIV) infection. Females who are pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OMP-59R5 plus Gemcitabine and Nab-Paclitaxel<br>OMP-59R5 plus Gemcitabine and Nab-Paclitaxel | Drug: OMP-59R5<br>* OMP-59R5 administered intravenously<br>Drug: Gemcitabine<br>* administered intravenously<br>Drug: Nab-Paclitaxel<br>* administered intravenously<br>* Other names: Abraxane;|
| Experimental: Gemcitabine and Nab-Paclitaxel plus Placebo<br>Gemcitabine and Nab-Paclitaxel plus Placebo | Drug: Gemcitabine<br>* administered intravenously<br>Drug: Placebo<br>* administered IV<br>Drug: Nab-Paclitaxel<br>* administered intravenously<br>* Other names: Abraxane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase Ib: Number of Participants With Dose-limiting Toxicities (DLT) | Number of participants with dose-limiting toxicities when administered OMP-59R5 every of other week (Days 1 and 15) in combination with nab-paclitaxel (Nab-P) 125 mg/m2 and gemcitabine (Gem) 1000 mg/m2 on Days 1, 8, and 15 of every 28-day cycle in subjects with previously untreated stage IV pancreatic cancer. In the event that no DLTs are observed, maximum tested dose would be considered the Maximum Tolerated Dose (MTD). | Up to 1 year in absence of unacceptable toxicity or disease progression. | 
| Phase 2: Overall Survival (ITT Population) | To determine the clinical benefit, as measured by overall survival (OS) ofthe addition of OMP-59R5 to nab-paclitaxel and gemcitabine in all subjects who are receiving first-line therapy for stage IV pancreatic cancer. | Up to 1 year in absence of unacceptable toxicity or disease progression. | 
| Phase 2: Median OS by Notch 3 Percentile (ITT Population) | To determine the clinical benefit, as measured by OS of the addition of OMP-59R5 to Nab-P+Gem across the 4 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 with Notch3 high expression level. | Up to 1 year in absence of unacceptable toxicity or disease progression. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Newly diagnosed Stage IV Pancreatic Cancer