A Study of Gemcitabine Plus Nab-paclitaxel With or Without FG-3019 in Participants With Locally Advanced, Unresectable Pancreatic Cancer

Study Overview
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Brief Summary
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This is a Phase 1/2 trial to evaluate the safety, tolerability, and efficacy of FG-3019 administered with gemcitabine and nab-paclitaxel in the treatment of locally advanced, unresectable pancreatic cancer.

Official Title
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A Randomized, Open Label, Phase 1/2 Trial of Gemcitabine Plus Nab-paclitaxel With or Without FG-3019 as Neoadjuvant Chemotherapy in Locally Advanced, Unresectable Pancreatic Cancer

Conditions
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Pancreatic Cancer (Unresectable)

Intervention / Treatment
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* Drug: FG-3019
* Drug: Gemcitabine
* Drug: Nab-paclitaxel


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male, or non-pregnant and, non-lactating female Histologically proven diagnosis of pancreatic ductal adenocarcinoma (PDAC) Radiographic and pathologic staging consistent with pancreatic cancer, locally advanced, unresectable (per National Comprehensive Cancer Network® [NCCN®] criteria) Laparoscopic confirmation that PDAC is locally advanced. Biliary stents are permitted. Measurable disease as defined by RECIST 1.1 Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Adequate liver, bone marrow, and renal function Agree to use contraception per protocol Less than Grade 2 pre-existing peripheral neuropathy Key Exclusion Criteria: Prior chemotherapy or radiation for pancreatic cancer Solid tumor contact with superior mesenteric artery (SMA) >180° Previous (within the past 5 years) or concurrent malignancy diagnosis (expect non-melanoma skin cancer and in situ carcinomas) Major surgery, within 4 weeks prior to Day 1 on study History of allergy or hypersensitivity to human, humanized or chimeric monoclonal antibodies Exposure to another investigational drug within 42 days of first dosing visit, or 5 half-lives of the study product (whichever is longer) Uncontrolled intercurrent illness Any medical condition that, in the opinion of the Investigator, may pose a safety risk to a participant in this trial, may confound the assessment of safety and efficacy, or may interfere with study participation. Current abuse of alcohol or drugs

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FG-3019 + Gemcitabine + Nab-paclitaxel<br>Participants will receive FG-3019 35 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion on Days 1 and 15 of each treatment cycle and on Day 8 of the first cycle, gemcitabine 1000 mg/square meter (m^2) and nab-paclitaxel 125 mg/m^2 by IV infusion on Days 1, 8, and 15 of each treatment cycle. Treatment will be administered over a 28-day cycle, for up to 6 cycles. | Drug: FG-3019<br>* FG-3019 will be administered per dose and schedule specified in the arm group description.<br>Drug: Gemcitabine<br>* Gemcitabine will be administered per dose and schedule specified in the arm group description.<br>* Other names: Gemzar;Drug: Nab-paclitaxel<br>* Nab-paclitaxel will be administered per dose and schedule specified in the arm group description.<br>* Other names: Abraxane;|
| Active Comparator: Gemcitabine + Nab-paclitaxel<br>Participants will receive gemcitabine 1000 mg/ meter squared (m^2) and nab-paclitaxel 125 mg/m^2 by IV infusion on Days 1, 8, and 15 of each treatment cycle. Treatment will be administered over a 28-day cycle, for up to 6 cycles. | Drug: Gemcitabine<br>* Gemcitabine will be administered per dose and schedule specified in the arm group description.<br>* Other names: Gemzar;Drug: Nab-paclitaxel<br>* Nab-paclitaxel will be administered per dose and schedule specified in the arm group description.<br>* Other names: Abraxane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A TEAE was defined as a new or worsening AE that occurred in the window of first infusion of any study drug (Day 1) and within 28 days of the last infusion of study drug or the day before surgery, whichever occurred first. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'. | From first infusion of any study drug (Day 1) up to 28 days after last infusion of study drug or the day before surgery (up to Day 196) | 
| Number of Participants Who Had Surgical Complications Post-Resection | Number of participants who had surgical complications (for example; surgical site infection, intra-abdominal abscess, or perioperative leak during surgery) has been reported | 30 days following discharge after surgery (up to Day 198) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Became Eligible for Surgery |  | After completion of 24 weeks of treatment with study drug | 
| Number of Participants in Whom R0 Resection Was Achieved | R0 resection was determined by pathological examination of the surgical specimen after resection. | After completion of 24 weeks of treatment with study drug | 
| Number of Participants in Whom R0 or R1 Resection Was Achieved | R0 or R1 resection was determined by pathological examination of the surgical specimen after resection. | After completion of 24 weeks of treatment with study drug | 
| Number of Participants With Complete Response (CR) or Partial Response (PR) Per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | CR was defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduced in short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | From randomization up to Week 52 | 
| Median Overall Survival | Overall survival was defined as the time from randomization until death from any cause. | From randomization until death from any cause, assessed up to 4 years | 
| Median Progression-Free Survival | Progression-free survival was defined as the time from randomization until objective tumor progression or death. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. | From randomization until objective tumor progression or death, assessed up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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locally, advanced, pancreatic, cancer, unresectable, pancreatic cancer