Back to resultsStudy to Evaluate the Efficacy and Safety of Andecaliximab Combined With Nivolumab Versus Nivolumab Alone in Adults With Unresectable or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma
Primary Purpose
Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Andecaliximab
Nivolumab
Sponsored by
About this trial
This is an interventional treatment trial for Gastric Adenocarcinoma
Eligibility Criteria
Key Inclusion Criteria:
- Histologically confirmed inoperable locally advanced or metastatic adenocarcinoma of the stomach or GEJ which have progressed on at least 1 prior systemic therapy or line of treatment for unresectable/metastatic disease
- Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 1
- Measurable disease according to Response Criteria in Solid Tumors (RECIST) v1.1
- Tumor sites that can be accessed for repeat biopsies
- Archival tumor tissue, preferably obtained from the most recent available biopsy; there must be adequate tissue for a Cochran-Mantel Haenszel (CMH) test stratified by programmed death ligand 1 (PD-L1) stratification test, as assessed by central pathologist
- Individuals not receiving anticoagulant medication must have an international normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin (aPTT) ≤ 1.5 x upper limit of normal (ULN)
- Required baseline laboratory data as outlined in protocol
Key Exclusion Criteria:
- Individuals who have received only neoadjuvant or adjuvant therapy for gastric adenocarcinoma
- Radiotherapy within 28 days of randomization
- Uncontrolled intercurrent illness as outlined in protocol
- History of a concurrent or second malignancy except for those outlined in protocol
- Major surgery, within 28 days of first dose of study drug
- Known positive status for human immunodeficiency virus (HIV)
- Known acute or chronic-active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
- Chronic daily treatment with oral corticosteroids (dose of > 10 mg/day prednisone equivalent) or other immunosuppressive medications within 14 days of randomization
- Known or suspected central nervous system metastases
- Documented myocardial infarction or unstable/uncontrolled cardiac disease within 6 months of randomization
- Serious systemic fungal, bacterial, viral, or other infection that is not controlled or requires intravenous antibiotics
- Current or history of pneumonitis or interstitial lung disease
- Active known or suspected autoimmune disease with exceptions noted in protocol.
- History of bone marrow, stem cell, or allogenic organ transplantation
NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Andecaliximab + Nivolumab
Nivolumab
Arm Description
Andecaliximab 800 mg plus nivolumab 3 mg/kg administered every 2 weeks until disease progression, unacceptable toxicity, or withdrawal of consent (up to 34 weeks at the time of the primary efficacy analysis; up to 101 weeks at the time of the safety follow-up analysis).
Nivolumab 3 mg/kg administered every 2 weeks until disease progression, unacceptable toxicity, or withdrawal of consent (up to 41 weeks at the time of the primary efficacy analysis; up to 97 weeks at the time of the safety follow-up analysis).
Outcomes
Primary Outcome Measures
Objective Response Rate (ORR)
ORR was defined as the percentage of participants with confirmed overall best response of complete response (CR) or partial response (PR) after starting study drug but before starting any new chemotherapy or radiotherapy as assessed by the investigator according to Response Criteria in Solid Tumors (RECIST) version 1.1. 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.
Secondary Outcome Measures
Progression Free Survival (PFS)
PFS was defined as the interval in months from the date of randomization to the earlier of the first documentation of definitive disease progression or death from any cause. The first definitive progressive disease (PD) was defined as the first radiation therapy, the first clinical PD, and the first confirmed imaging PD, whichever came first. Participants without PD or death and participants with PD after starting new anti-cancer therapy are censored at the last tumor assessment date.
Overall Survival (OS)
OS was defined as the interval from the date of randomization to death from any cause. Surviving participants are censored at the last date known alive.
Duration of Response (DOR)
DOR was defined as the interval from the date of the first response (complete or partial response) was achieved to the earlier of the first documentation of definitive disease progression or death from any cause.
Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a clinical study participants administered a medicinal product, which does not necessarily have a causal relationship with the treatment. TEAEs are events that are defined as AEs with onset dates on or after the first dose of andecaliximab/nivolumab and up to 30 days after permanent discontinuation of andecaliximab or 5 months after permanent discontinuation of nivolumab, or led to premature discontinuation of andecaliximab or nivolumab.
Percentage of Participants Who Experienced Treatment-emergent Laboratory Abnormalities
Treatment-emergent (Chemistry, Hematology, Coagulation, and Urinalysis) 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 postbaseline time point, up to and including the date of the last dose of andecaliximab plus 30 days or nivolumab plus 5 months. If the relevant baseline laboratory value is missing, any abnormality of at least Grade 1 observed within the time frame specified above will be considered treatment-emergent. Percentage of participants with any postbaseline Grade 1 or higher laboratory abnormality is reported.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02864381
Brief Title
Study to Evaluate the Efficacy and Safety of Andecaliximab Combined With Nivolumab Versus Nivolumab Alone in Adults With Unresectable or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma
Official Title
A Phase 2, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of GS-5745 Combined With Nivolumab Versus Nivolumab Alone in Subjects With Unresectable or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
September 1, 2016 (Actual)
Primary Completion Date
November 8, 2017 (Actual)
Study Completion Date
August 23, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of this study is to evaluate and compare the efficacy of andecaliximab (GS-5745) in combination with nivolumab versus nivolumab alone in adults with recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
144 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Andecaliximab + Nivolumab
Arm Type
Experimental
Arm Description
Andecaliximab 800 mg plus nivolumab 3 mg/kg administered every 2 weeks until disease progression, unacceptable toxicity, or withdrawal of consent (up to 34 weeks at the time of the primary efficacy analysis; up to 101 weeks at the time of the safety follow-up analysis).
Arm Title
Nivolumab
Arm Type
Active Comparator
Arm Description
Nivolumab 3 mg/kg administered every 2 weeks until disease progression, unacceptable toxicity, or withdrawal of consent (up to 41 weeks at the time of the primary efficacy analysis; up to 97 weeks at the time of the safety follow-up analysis).
Intervention Type
Drug
Intervention Name(s)
Andecaliximab
Other Intervention Name(s)
GS-5745
Intervention Description
800 mg administered via IV infusion
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Intervention Description
3 mg/kg administered via IV infusion
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
ORR was defined as the percentage of participants with confirmed overall best response of complete response (CR) or partial response (PR) after starting study drug but before starting any new chemotherapy or radiotherapy as assessed by the investigator according to Response Criteria in Solid Tumors (RECIST) version 1.1. 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.
Time Frame
Up to 41 weeks
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
PFS was defined as the interval in months from the date of randomization to the earlier of the first documentation of definitive disease progression or death from any cause. The first definitive progressive disease (PD) was defined as the first radiation therapy, the first clinical PD, and the first confirmed imaging PD, whichever came first. Participants without PD or death and participants with PD after starting new anti-cancer therapy are censored at the last tumor assessment date.
Time Frame
Andecaliximab + Nivolumab median follow-up time: 7.0 months; Nivolumab median follow-up time: 7.1 months
Title
Overall Survival (OS)
Description
OS was defined as the interval from the date of randomization to death from any cause. Surviving participants are censored at the last date known alive.
Time Frame
Andecaliximab + Nivolumab median follow-up time: 7.0 months; Nivolumab median follow-up time: 7.0 months
Title
Duration of Response (DOR)
Description
DOR was defined as the interval from the date of the first response (complete or partial response) was achieved to the earlier of the first documentation of definitive disease progression or death from any cause.
Time Frame
Andecaliximab + Nivolumab median follow-up time: 7.0 months; Nivolumab median follow-up time: 7.1 months
Title
Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
Description
An adverse event (AE) is any untoward medical occurrence in a clinical study participants administered a medicinal product, which does not necessarily have a causal relationship with the treatment. TEAEs are events that are defined as AEs with onset dates on or after the first dose of andecaliximab/nivolumab and up to 30 days after permanent discontinuation of andecaliximab or 5 months after permanent discontinuation of nivolumab, or led to premature discontinuation of andecaliximab or nivolumab.
Time Frame
Andecaliximab: First dose date up to last dose (maximum: 101 weeks) + 30 days; Nivolumab: First dose date up to last dose (maximum: 101 weeks) + 5 months
Title
Percentage of Participants Who Experienced Treatment-emergent Laboratory Abnormalities
Description
Treatment-emergent (Chemistry, Hematology, Coagulation, and Urinalysis) 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 postbaseline time point, up to and including the date of the last dose of andecaliximab plus 30 days or nivolumab plus 5 months. If the relevant baseline laboratory value is missing, any abnormality of at least Grade 1 observed within the time frame specified above will be considered treatment-emergent. Percentage of participants with any postbaseline Grade 1 or higher laboratory abnormality is reported.
Time Frame
Andecaliximab: First dose date up to last dose (maximum: 101 weeks) + 30 days; Nivolumab: First dose date up to last dose (maximum: 101 weeks) + 5 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Histologically confirmed inoperable locally advanced or metastatic adenocarcinoma of the stomach or GEJ which have progressed on at least 1 prior systemic therapy or line of treatment for unresectable/metastatic disease
Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 1
Measurable disease according to Response Criteria in Solid Tumors (RECIST) v1.1
Tumor sites that can be accessed for repeat biopsies
Archival tumor tissue, preferably obtained from the most recent available biopsy; there must be adequate tissue for a Cochran-Mantel Haenszel (CMH) test stratified by programmed death ligand 1 (PD-L1) stratification test, as assessed by central pathologist
Individuals not receiving anticoagulant medication must have an international normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin (aPTT) ≤ 1.5 x upper limit of normal (ULN)
Required baseline laboratory data as outlined in protocol
Key Exclusion Criteria:
Individuals who have received only neoadjuvant or adjuvant therapy for gastric adenocarcinoma
Radiotherapy within 28 days of randomization
Uncontrolled intercurrent illness as outlined in protocol
History of a concurrent or second malignancy except for those outlined in protocol
Major surgery, within 28 days of first dose of study drug
Known positive status for human immunodeficiency virus (HIV)
Known acute or chronic-active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
Chronic daily treatment with oral corticosteroids (dose of > 10 mg/day prednisone equivalent) or other immunosuppressive medications within 14 days of randomization
Known or suspected central nervous system metastases
Documented myocardial infarction or unstable/uncontrolled cardiac disease within 6 months of randomization
Serious systemic fungal, bacterial, viral, or other infection that is not controlled or requires intravenous antibiotics
Current or history of pneumonitis or interstitial lung disease
Active known or suspected autoimmune disease with exceptions noted in protocol.
History of bone marrow, stem cell, or allogenic organ transplantation
NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46845
Country
United States
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
City
Albury
State/Province
New South Wales
ZIP/Postal Code
2640
Country
Australia
City
Wahroonga
State/Province
New South Wales
ZIP/Postal Code
2076
Country
Australia
City
Douglas
State/Province
Queensland
ZIP/Postal Code
4818
Country
Australia
City
Hobart
State/Province
Tasmania
ZIP/Postal Code
7000
Country
Australia
City
La Louvière
State/Province
Hainaut
ZIP/Postal Code
7100
Country
Belgium
City
Gent
State/Province
Oost-Vlaanderen
ZIP/Postal Code
9000
Country
Belgium
City
Leuven
State/Province
Vlaams Brabant
ZIP/Postal Code
3000
Country
Belgium
City
Brest
State/Province
Finistère
ZIP/Postal Code
29609
Country
France
City
Reims
State/Province
Marne
ZIP/Postal Code
51092
Country
France
City
Villejuif
State/Province
Val-de-Marne
ZIP/Postal Code
94805
Country
France
City
Budapest
ZIP/Postal Code
H-1097
Country
Hungary
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
City
Meldola
State/Province
Forli-Cesena
ZIP/Postal Code
47014
Country
Italy
City
Genova
State/Province
Ligura
ZIP/Postal Code
16128
Country
Italy
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20132
Country
Italy
City
Pisa
State/Province
Toscana
ZIP/Postal Code
56126
Country
Italy
City
Brzozow
State/Province
Podkarpackie
ZIP/Postal Code
36-200
Country
Poland
City
Poznań
ZIP/Postal Code
60-693
Country
Poland
City
Warszawa
ZIP/Postal Code
02-781
Country
Poland
City
Majadahonda
State/Province
Madrid
ZIP/Postal Code
28222
Country
Spain
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
City
Bristol
ZIP/Postal Code
BS2 8ED
Country
United Kingdom
City
Edgbaston
ZIP/Postal Code
B15 2PR
Country
United Kingdom
City
London
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom
City
London
ZIP/Postal Code
WC1E 6BT
Country
United Kingdom
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
City
Sutton
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34893523
Citation
Shah MA, Cunningham D, Metges JP, Van Cutsem E, Wainberg Z, Elboudwarej E, Lin KW, Turner S, Zavodovskaya M, Inzunza D, Liu J, Patterson SD, Zhou J, He J, Thai D, Bhargava P, Brachmann CB, Cantenacci DVT. Randomized, open-label, phase 2 study of andecaliximab plus nivolumab versus nivolumab alone in advanced gastric cancer identifies biomarkers associated with survival. J Immunother Cancer. 2021 Dec;9(12):e003580. doi: 10.1136/jitc-2021-003580.
Results Reference
derived
Learn more about this trial
Study to Evaluate the Efficacy and Safety of Andecaliximab Combined With Nivolumab Versus Nivolumab Alone in Adults With Unresectable or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma
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