Safety and Efficacy Study of AVB-S6-500 (Batiraxcept) in Patients With Advanced Pancreatic Adenocarcinoma

Study Overview
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Brief Summary
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This is a Phase 1b/2 study of batiraxcept (AVB-S6-500) designed to evaluate the safety and efficacy of batiraxcept in combination with nab-paclitaxel and gemcitabine in subjects with locally advanced, recurrent, or metastatic pancreatic adenocarcinoma as first line therapy. The phase 1b portion of the study is open label and patients will receive batiraxcept, nab-paclitaxel, and gemcitabine. The Phase 2 portion of the study is randomized, 2-arm, open-label study to compare efficacy and tolerability of batiraxcept, nab-paclitaxel, and gemcitabine versus nab-paclitaxel and gemcitabine as first line therapy.

Official Title
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A Phase 1b/2 Randomized Study of AVB-S6-500 Plus Nab-paclitaxel and Gemcitabine in Patients With Locally Advanced or Metastatic Pancreatic Adenocarcinoma

Conditions
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Pancreatic Adenocarcinoma

Intervention / Treatment
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* Drug: batiraxcept
* Drug: Nab paclitaxel
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older Histologically or cytologically confirmed pancreatic adenocarcinoma. Must have locally advanced, recurrent, or metastatic disease ineligible for curative intent treatment(s) and eligible for first line systemic treatment. Must have radiologic imaging with a computed tomography (CT) scan or magnetic resonance imaging (MRI) within 22 days of study entry Must have at least one measurable lesion according to RECIST 1.1 Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Adequate gastrointestinal (GI), bone marrow, liver and kidney function Life expectancy minimum of > 12 weeks Adequate recovery from surgery to Grade 1 or baseline with at least 28 days from time of major surgery Exclusion Criteria: Received last dose of chemotherapy (neoadjuvant or adjuvant), surgery, or radiation treatment with curative intent within 6 months prior to study entry Islet-cell neoplasms Prior malignancy within the past 3 years except adequately treated basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the prostate, cervix, breast or melanoma Symptomatic uncontrolled central nervous system (CNS) metastasis or brain metastases unless adequately treated and controlled Evidence of clinically significant third spacing (e.g. pleural effusion, ascites, anasarca, etc.) within 28 days prior to study entry Serious active infection requiring IV antibiotics and/or hospitalization at study entry Active human immune deficiency (HIV) syndrome, hepatitis B, hepatitis C, or other active viral illness

Ages Eligible for Study
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Minimum Age: 18 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1b: batiraxcept+ nab-paclitaxel and gemcitabine<br>Up to three dose levels of bactiraxcept plus nab-paclitaxel and gemcitabine | Drug: batiraxcept<br>* Batiraxcept is experimental drug<br>* Other names: AVB-S6-500;Drug: Nab paclitaxel<br>* Nab paclitaxel is active comparator<br>* Other names: Abraxane;Drug: Gemcitabine<br>* Gemcitabine is active comparator<br>|
| Experimental: Phase 2: batiraxcept+ nab-paclitaxel and gemcitabine<br> | Drug: batiraxcept<br>* Batiraxcept is experimental drug<br>* Other names: AVB-S6-500;Drug: Nab paclitaxel<br>* Nab paclitaxel is active comparator<br>* Other names: Abraxane;Drug: Gemcitabine<br>* Gemcitabine is active comparator<br>|
| Active Comparator: Phase 2: nab-paclitaxel and gemcitabine alone<br> | Drug: Nab paclitaxel<br>* Nab paclitaxel is active comparator<br>* Other names: Abraxane;Drug: Gemcitabine<br>* Gemcitabine is active comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) | Measured by the number of patients with AEs in Phase 1b portion of the study. | 12 months | 
| Anti-tumor activity of batiraxcept in combination with nab-paclitaxel and gemcitabine in Phase 1b portion of the study | Measured by Objective Response Rate (ORR): Proportion of subjects who have a partial or complete response to therapy relative to baseline in Phase 1b portion of the study. | 12 months | 
| Anti-tumor activity of batiraxcept in combination with nab-paclitaxel and gemcitabine in Phase 2 portion of the study | Measured by progression free survival (PFS) in patients receiving batiraxcept, nab-paclitaxel, and gemcitabine versus patients receiving nab-paclitaxel, and gemcitabine alone in Phase 2. | 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: AUC | Area under the batiraxcept concentration-time curve. | 30 months | 
| Pharmacokinetics: Cmax | Maximum observed batiraxcept concentration. | 30 months | 
| Pharmacokinetics: Tmax | Time of maximum observed batiraxcept concentration. | 30 months | 
| Pharmacokinetics: t1/2 | Apparent terminal half-life of batiraxcept. | 30 months | 
| Pharmacodynamic marker assessment | Change from the baseline in GAS6 serum levels. | 30 months | 
| Anti-drug antibody (ADA) titers | Change from baseline in ADA titer. | 30 months | 
| Disease control rate | Proportion of subjects who have a complete or partial response to therapy or maintain stable disease. | 30 months | 
| Duration of response (DOR) | Measured from the date of partial or complete response to therapy until the cancer progresses. | 30 months | 
| Overall survival | Time following the treatment until death. | 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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locally advanced, recurrent, metastatic, pancreatic, exocrine, pancreas, adenocarcinoma