Andecaliximab With mFOLFOX6 as First Line Treatment for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

Study Overview
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Brief Summary
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The primary objective of this study is to compare the efficacy of andecaliximab (GS-5745) versus placebo in combination with modified fluorouracil (5-FU), leucovorin (LV), and oxaliplatin (OXA) (mFOLFOX6) as measured by overall survival.

Official Title
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A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GS-5745 Combined With mFOLFOX6 as First Line Treatment in Patients With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

Conditions
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Gastric Adenocarcinoma

Intervention / Treatment
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* Drug: Andecaliximab
* Drug: Placebo
* Drug: Leucovorin
* Drug: 5-fluorouracil
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Adults with histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction that is inoperable, locally advanced or metastatic and not amenable to curative therapy Adequate hematologic, liver, coagulation and kidney function Eastern Cooperative Oncology Group (ECOG) ≤ 1 Evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 Key Exclusion Criteria: Previous chemotherapy for locally advanced or metastatic gastric cancer. Human Epidermal Growth Factor Receptor 2 (HER2)-positive gastric cancer HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection Pregnant or breast feeding women Individuals with known or suspected central nervous system metastases or individuals requiring chronic daily treatment with oral corticosteroids Grade ≥ 2 peripheral neuropathy Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Andecaliximab<br>Andecaliximab plus mFOLFOX6 (LV+5-FU+OXA) during Cycles 1-6, followed by andecaliximab plus LV+5-FU during subsequent cycles | Drug: Andecaliximab<br>* 800 mg administered intravenously on Days 1 and 15 of each 28-day treatment cycle<br>* Other names: GS-5745;Drug: Leucovorin<br>* Administered intravenously per standard of care on Days 1 and 15 of each treatment cycle<br>* Other names: LV;Drug: 5-fluorouracil<br>* Administered intravenously per standard of care on Days 1 and 15 of each treatment cycle<br>* Other names: 5-FU;Drug: Oxaliplatin<br>* Administered intravenously per standard of care on Days 1 and 15 of each treatment cycle<br>* Other names: OXA;|
| Placebo Comparator: Placebo<br>Placebo plus mFOLFOX6 (LV+5-FU+OXA) during Cycles 1-6, followed by placebo plus LV+5-FU during subsequent cycles | Drug: Placebo<br>* Administered intravenously on Days 1 and 15 of each treatment cycle<br>Drug: Leucovorin<br>* Administered intravenously per standard of care on Days 1 and 15 of each treatment cycle<br>* Other names: LV;Drug: 5-fluorouracil<br>* Administered intravenously per standard of care on Days 1 and 15 of each treatment cycle<br>* Other names: 5-FU;Drug: Oxaliplatin<br>* Administered intravenously per standard of care on Days 1 and 15 of each treatment cycle<br>* Other names: OXA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was defined as the time interval from the date of randomization to death from any cause. | Andecaliximab + mFOLFOX6 median follow-up at the time of final analysis: 19.43 months; Placebo + mFOLFOX6 median follow-up at the time of the final analysis: 19.45 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS was defined as the interval of time from the date of randomization to the earlier of the first documentation of definitive disease progression or death from any cause. | Andecaliximab + mFOLFOX6 median follow-up at the time of the final analysis: 18.64 months; Placebo + mFOLFOX6 median follow-up at the time of the final analysis: 18.74 months | 
| Objective Response Rate (ORR) | ORR was defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. CR was defined as the disappearance of all target lesions and disappearance of all non-target lesions and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | Up to 135.4 weeks at the time of final analysis | 
| Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal product, which does not necessarily have a causal relationship with the treatment. TEAEs are events in a given study period that meet any of the following criteria: Any AE with onset date of on or after andecalizimab/placebo start date and no later than 30 days after permanent discontinuation of all study treatment (andecaliximab/placebo and chemotherapy) or Any AEs with onset date of on or after the andecaliximab/placebo start date and no later than 55 days after permanent discontinuation of andecaliximab/placebo or AEs leading to discontinuation of andecaliximab/placebo. | First dose date up to the last dose date (maximum:161.7 weeks) plus 30 to 55 days | 
| Percentage of Participants With Clinically Relevant Treatment-emergent Laboratory Abnormalities | Treatment-emergent laboratory abnormalities were graded per Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 where 0=None, 1=Mild, 2=Moderate, 3=Severe, 4=Potentially Life Threatening. Treatment-emergent laboratory abnormalities are defined as values that increase at least 1 toxicity grade from baseline at any post-baseline time point, up to 30 days after the last dose of all study treatment, or 55 days after the last dose of andecaliximab/placebo for participants who permanently discontinued all study treatments. If the relevant baseline laboratory value is missing, then any abnormality of at least Grade 1 was considered treatment-emergent. | First dose date up to the last dose date (maximum: 161.7 weeks) plus 30 to 55 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastroesophageal junction (GEJ), Stomach cancer