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

Tracking Information

• First Submitted Date: August 10, 2016
• First Posted Date: August 12, 2016
• Results First Submitted Date: August 18, 2020
• Results First Posted Date: September 18, 2020
• Last Update Posted Date: September 18, 2020
• Actual Study Start Date: September 1, 2016
• Actual Primary Completion Date: November 8, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 17, 2020)

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.

Original Primary Outcome Measures (submitted: August 10, 2016)

Objective Response Rate [ Time Frame: Up to 2 years ]

Objective response rate will be determined from the participants' best response during treatment.

Current Secondary Outcome Measures (submitted: September 17, 2020)

• 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.
• 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.
• 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.
• 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.
• 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.

Original Secondary Outcome Measures (submitted: August 10, 2016)

• Progression Free Survival [ Time Frame: Up to 2 years ]
  Progression free survival is defined as the interval from the date of randomization to the earlier of the first documentation of definitive disease progression or death from any cause.
• Overall Survival [ Time Frame: Up to 5 years ]
  Overall survival is defined as the interval from date of randomization to death from any cause.
• Duration of Response [ Time Frame: Up to 2 years ]
  Duration of response is defined as the interval from the date of the first response (complete response or partial response) is achieved to the earlier of the first documentation of definitive disease progression or death from any cause.
• Occurrence of Adverse Events and Laboratory Abnormalities During Treatment [ Time Frame: Up to 2 years ]
  The occurrence of adverse events and laboratory abnormalities will be presented as the percentage of participants who experience treatment-emergent adverse events or treatment-emergent laboratory abnormalities.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Gastric Adenocarcinoma
• Gastroesophageal Junction Adenocarcinoma

Intervention

• Drug: Andecaliximab
  800 mg administered via IV infusion
  Other Name: GS-5745
• Drug: Nivolumab
  3 mg/kg administered via IV infusion

Study Arms

• 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).
  Interventions:

  • Drug: Andecaliximab
  • Drug: Nivolumab
• 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).
  Intervention: Drug: Nivolumab

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 7, 2017): 144
• Original Estimated Enrollment (submitted: August 10, 2016): 120
• Actual Study Completion Date: August 23, 2019
• Actual Primary Completion Date: November 8, 2017 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, France, Hungary, Italy, Poland, Spain, United Kingdom, United States
• Removed Location Countries: Germany

Administrative Information

• NCT Number: NCT02864381
• Other Study ID Numbers: GS-US-296-2013; 2016-001402-41 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: September 2020