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

• ClinicalTrials.gov Identifier: NCT02864381
• Recruitment Status: Completed
• First Posted: August 12, 2016
• Results First Posted: September 18, 2020
• Last Update Posted: September 18, 2020
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

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.

Condition or disease	Intervention/treatment	Phase
Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma	Drug: Andecaliximab; Drug: Nivolumab	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 144 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 1, 2016
• Actual Primary Completion Date: November 8, 2017
• Actual Study Completion Date: August 23, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Andecaliximab + Nivolumab; 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).	Drug: Andecaliximab; 800 mg administered via IV infusion; Other Name: GS-5745; Drug: Nivolumab; 3 mg/kg administered via IV infusion
Active Comparator: Nivolumab; 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).	Drug: Nivolumab; 3 mg/kg administered via IV infusion

Outcome Measures

Primary Outcome Measures :

1. Objective Response Rate (ORR) [ Time Frame: Up to 41 weeks ]
   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 :

1. Progression Free Survival (PFS) [ Time Frame: Andecaliximab + Nivolumab median follow-up time: 7.0 months; Nivolumab median follow-up time: 7.1 months ]
   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.
2. Overall Survival (OS) [ Time Frame: Andecaliximab + Nivolumab median follow-up time: 7.0 months; Nivolumab median follow-up time: 7.0 months ]
   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.
3. Duration of Response (DOR) [ Time Frame: Andecaliximab + Nivolumab median follow-up time: 7.0 months; Nivolumab median follow-up time: 7.1 months ]
   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.
4. Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) [ 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 ]
   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.
5. Percentage of Participants Who Experienced Treatment-emergent Laboratory Abnormalities [ 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 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

Los Angeles, California, United States, 90095

San Francisco, California, United States, 94158

United States, Illinois

Chicago, Illinois, United States, 60637

United States, Indiana

Fort Wayne, Indiana, United States, 46845

United States, Missouri

Saint Louis, Missouri, United States, 63110

United States, New York

New York, New York, United States, 10065

Australia, New South Wales

Albury, New South Wales, Australia, 2640

Wahroonga, New South Wales, Australia, 2076

Australia, Queensland

Douglas, Queensland, Australia, 4818

Australia, Tasmania

Hobart, Tasmania, Australia, 7000

Belgium

La Louvière, Hainaut, Belgium, 7100

Gent, Oost-Vlaanderen, Belgium, 9000

Leuven, Vlaams Brabant, Belgium, 3000

France

Brest, Finistère, France, 29609

Reims, Marne, France, 51092

Villejuif, Val-de-Marne, France, 94805

Hungary

Budapest, Hungary, H-1097

Debrecen, Hungary, 4032

Italy

Meldola, Forli-Cesena, Italy, 47014

Genova, Ligura, Italy, 16128

Milano, Lombardia, Italy, 20132

Pisa, Toscana, Italy, 56126

Poland

Brzozow, Podkarpackie, Poland, 36-200

Poznań, Poland, 60-693

Warszawa, Poland, 02-781

Spain

Majadahonda, Madrid, Spain, 28222

Barcelona, Spain, 08003

Barcelona, Spain, 08035

United Kingdom

Bristol, United Kingdom, BS2 8ED

Edgbaston, United Kingdom, B15 2PR

London, United Kingdom, EC1A 7BE

London, United Kingdom, WC1E 6BT

Manchester, United Kingdom, M20 4BX

Sutton, United Kingdom, SM2 5PT

Sponsors and Collaborators

Gilead Sciences

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

  Study Documents (Full-Text)

Documents provided by Gilead Sciences:

Study Protocol  [PDF] June 16, 2017

Statistical Analysis Plan: Final  [PDF] December 6, 2017

Statistical Analysis Plan: Follow-up Analysis  [PDF] June 28, 2019

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02864381
• Other Study ID Numbers: GS-US-296-2013; 2016-001402-41 ( EudraCT Number )
• First Posted: August 12, 2016
• Results First Posted: September 18, 2020
• Last Update Posted: September 18, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Adenocarcinoma; Esophageal Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Nivolumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action