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

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02864381
• Collaborator: (none)
• Enrollment: 144
• Locations: 34
• Arms: 2
• Actual Duration (Months): 35.7
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.1

Study Details

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
• 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: Sep 1, 2016
• Actual Primary Completion Date: Nov 8, 2017
• Actual Study Completion Date: Aug 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 Names: 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) [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) [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) [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) [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) [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 [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

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1		Los Angeles	California	United States	90095
2		San Francisco	California	United States	94158
3		Chicago	Illinois	United States	60637
4		Fort Wayne	Indiana	United States	46845
5		Saint Louis	Missouri	United States	63110
6		New York	New York	United States	10065
7		Albury	New South Wales	Australia	2640
8		Wahroonga	New South Wales	Australia	2076
9		Douglas	Queensland	Australia	4818
10		Hobart	Tasmania	Australia	7000
11		La Louvière	Hainaut	Belgium	7100
12		Gent	Oost-Vlaanderen	Belgium	9000
13		Leuven	Vlaams Brabant	Belgium	3000
14		Brest	Finistère	France	29609
15		Reims	Marne	France	51092
16		Villejuif	Val-de-Marne	France	94805
17		Budapest		Hungary	H-1097
18		Debrecen		Hungary	4032
19		Meldola	Forli-Cesena	Italy	47014
20		Genova	Ligura	Italy	16128
21		Milano	Lombardia	Italy	20132
22		Pisa	Toscana	Italy	56126
23		Brzozow	Podkarpackie	Poland	36-200
24		Poznań		Poland	60-693
25		Warszawa		Poland	02-781
26		Majadahonda	Madrid	Spain	28222
27		Barcelona		Spain	08003
28		Barcelona		Spain	08035
29		Bristol		United Kingdom	BS2 8ED
30		Edgbaston		United Kingdom	B15 2PR
31		London		United Kingdom	EC1A 7BE
32		London		United Kingdom	WC1E 6BT
33		Manchester		United Kingdom	M20 4BX
34		Sutton		United Kingdom	SM2 5PT

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

• Study Protocol - Jun 16, 2017
• Statistical Analysis Plan: Final - Dec 6, 2017
• Statistical Analysis Plan: Follow-up Analysis - Jun 28, 2019

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02864381
• Other Study ID Numbers: GS-US-296-2013; 2016-001402-41
• First Posted: Aug 12, 2016
• Last Update Posted: Sep 18, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• 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; Nivolumab

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in Australia, Europe, and the United States. The first participant was screened on 01 September 2016. The last study visit occurred on 23 August 2019.
Pre-assignment Detail	187 participants were screened.

Arm/Group Title	Andecaliximab + Nivolumab	Nivolumab
Arm/Group Description	Andecaliximab 800 mg administered via intravenous (IV) infusion plus nivolumab 3 mg/kg administered via IV infusion 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 via IV infusion 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).
Period Title: Overall Study
STARTED	72	72
COMPLETED	0	0
NOT COMPLETED	72	72

Baseline Characteristics

Arm/Group Title	Andecaliximab + Nivolumab	Nivolumab	Total
Arm/Group Description	Andecaliximab 800 mg administered via intravenous (IV) infusion plus nivolumab 3 mg/kg administered via IV infusion 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 via IV infusion 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).	Total of all reporting groups
Overall Participants	72	72	144
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58 (12.1)	59 (11.8)	59 (11.9)
Sex: Female, Male (Count of Participants)
Female	23 31.9%	22 30.6%	45 31.3%
Male	49 68.1%	50 69.4%	99 68.8%
Race/Ethnicity, Customized (Count of Participants)
Asian	1 1.4%	1 1.4%	2 1.4%
Black	2 2.8%	0 0%	2 1.4%
White	55 76.4%	61 84.7%	116 80.6%
Not Permitted	12 16.7%	8 11.1%	20 13.9%
Other	2 2.8%	2 2.8%	4 2.8%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	2 2.8%	3 4.2%	5 3.5%
Not Hispanic or Latino	59 81.9%	61 84.7%	120 83.3%
Not Permitted	11 15.3%	8 11.1%	19 13.2%
Region of Enrollment (participants) [Number]
United Kingdom	17 23.6%	18 25%	35 24.3%
United States	14 19.4%	14 19.4%	28 19.4%
Belgium	5 6.9%	10 13.9%	15 10.4%
France	9 12.5%	6 8.3%	15 10.4%
Poland	5 6.9%	9 12.5%	14 9.7%
Spain	10 13.9%	4 5.6%	14 9.7%
Italy	8 11.1%	5 6.9%	13 9%
Australia	2 2.8%	5 6.9%	7 4.9%
Hungary	2 2.8%	1 1.4%	3 2.1%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The Intent-to-treat Analysis Set included all participants who were randomized in the study.

Arm/Group Title	Andecaliximab + Nivolumab	Nivolumab
Arm/Group Description	Andecaliximab 800 mg administered via intravenous (IV) infusion plus nivolumab 3 mg/kg administered via IV infusion 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 via IV infusion 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).
Measure Participants	72	72
Mean (95% Confidence Interval) [percentage of participants]	9.7 13.5%	6.9 9.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Andecaliximab + Nivolumab, Nivolumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8
	Comments	P-value is derived from Cochran-Mantel Haenszel (CMH) test stratified by programmed death ligand 1 (PD-L1) stratification factor status.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; 0.4 to 6.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds Ratio is derived from CMH test stratified by PD-L1 stratification factor status, the Nivolumab alone arm serves as the reference.

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants in the Intent-to-treat Analysis Set were analyzed.

Arm/Group Title	Andecaliximab + Nivolumab	Nivolumab
Arm/Group Description	Andecaliximab 800 mg administered via intravenous (IV) infusion plus nivolumab 3 mg/kg administered via IV infusion 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 via IV infusion 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).
Measure Participants	72	72
Median (95% Confidence Interval) [months]	1.840	1.856

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Andecaliximab + Nivolumab, Nivolumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.306
	Comments	P-value is derived from log-rank test stratified by PD-L1 stratification factor status.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.836
	Confidence Interval	(2-Sided) 95%; 0.589 to 1.189
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio is derived from Cox model stratified by PD-L1 stratification factor status, the Nivolumab alone arm serves as the reference.

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants in the Intent-to-treat Analysis Set were analyzed.

Arm/Group Title	Andecaliximab + Nivolumab	Nivolumab
Arm/Group Description	Andecaliximab 800 mg administered via intravenous (IV) infusion plus nivolumab 3 mg/kg administered via IV infusion 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 via IV infusion 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).
Measure Participants	72	72
Median (95% Confidence Interval) [months]	7.162	5.881

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Andecaliximab + Nivolumab, Nivolumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.312
	Comments	P-value is derived from log-rank test stratified by PD-L1 stratification factor status.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.786
	Confidence Interval	(2-Sided) 95%; 0.491 to 1.257
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio is derived from Cox model stratified by PD-L1 stratification factor status, the Nivolumab alone arm serves as the reference.

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants in the Intent-to-treat Analysis Set who achieved CR or PR were analyzed.

Arm/Group Title	Andecaliximab + Nivolumab	Nivolumab
Arm/Group Description	Andecaliximab 800 mg administered via intravenous (IV) infusion plus nivolumab 3 mg/kg administered via IV infusion 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 via IV infusion 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).
Measure Participants	7	5
Median (95% Confidence Interval) [months]	NA	NA

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Andecaliximab + Nivolumab	Nivolumab
Arm/Group Description	Andecaliximab 800 mg administered via intravenous (IV) infusion plus nivolumab 3 mg/kg administered via IV infusion 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 via IV infusion 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).
Measure Participants	71	70
Number [percentage of participants]	98.6 136.9%	97.1 134.9%

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	Andecaliximab + Nivolumab	Nivolumab
Arm/Group Description	Andecaliximab 800 mg administered via intravenous (IV) infusion plus nivolumab 3 mg/kg administered via IV infusion 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 via IV infusion 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).
Measure Participants	71	70
Alanine aminotransferase increased	20.0 27.8%	27.1 37.6%
Alkaline phosphatase increased	45.1 62.6%	40.0 55.6%
Aspartate aminotransferase increased	30.0 41.7%	28.6 39.7%
Blood bilirubin increased	8.5 11.8%	11.4 15.8%
Chronic Kidney Disease	16.9 23.5%	25.7 35.7%
Creatinine increased	1.4 1.9%	7.1 9.9%
Hyperglycemia	22.5 31.3%	18.6 25.8%
Hyperkalemia	7.1 9.9%	5.7 7.9%
Hypermagnesemia	2.8 3.9%	1.4 1.9%
Hypoalbuminemia	35.2 48.9%	38.6 53.6%
Hypoglycemia	11.3 15.7%	4.3 6%
Hypokalemia	10.0 13.9%	11.4 15.8%
Hypomagnesemia	5.6 7.8%	4.3 6%
Hyponatremia	28.2 39.2%	40.0 55.6%
Hypophosphatemia	11.3 15.7%	8.6 11.9%
Lipase increased	11.3 15.7%	8.6 11.9%
Serum amylase increased	9.9 13.8%	7.1 9.9%
Activated partial thromboplastin time prolonged	2.6 3.6%	19.4 26.9%
International Normalized Ratio (INR) increased	2.6 3.6%	12.5 17.4%
Anemia	53.5 74.3%	56.5 78.5%
Lymphocytes, Typical count decreased	35.2 48.9%	27.5 38.2%
Lymphocytes, Typical count increased	4.2 5.8%	0 0%
Neutrophil count decreased	5.6 7.8%	5.8 8.1%
Platelet count decreased	8.5 11.8%	5.8 8.1%
White blood cell decreased	9.9 13.8%	7.2 10%
Proteinuria (Dipstick)	29.4 40.8%	31.3 43.5%

Adverse Events

Time Frame	All-Cause Mortality: Andecaliximab + Nivolumab median follow-up time: 28.2 months; Nivolumab median follow-up time: 28.4 months; Adverse Events: 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
Adverse Event Reporting Description	All-Cause Mortality: The Intent-to treat Analysis Set included all participants randomized in the study. Adverse Events:The Safety Analysis Set included all participants who received at least 1 dose of study drug.
Arm/Group Title	Andecaliximab + Nivolumab		Nivolumab
Arm/Group Description	Andecaliximab 800 mg administered via intravenous (IV) infusion plus nivolumab 3 mg/kg administered via IV infusion 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 via IV infusion 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).
All Cause Mortality
	Andecaliximab + Nivolumab		Nivolumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/72 (84.7%)		62/72 (86.1%)
Serious Adverse Events
	Andecaliximab + Nivolumab		Nivolumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/71 (59.2%)		38/70 (54.3%)
Blood and lymphatic system disorders
Anaemia	5/71 (7%)		4/70 (5.7%)
Cardiac disorders
Ventricular fibrillation	0/71 (0%)		1/70 (1.4%)
Endocrine disorders
Hypophysitis	1/71 (1.4%)		0/70 (0%)
Eye disorders
Retinal disorder	1/71 (1.4%)		0/70 (0%)
Gastrointestinal disorders
Abdominal pain	3/71 (4.2%)		6/70 (8.6%)
Abdominal pain upper	1/71 (1.4%)		1/70 (1.4%)
Anal haemorrhage	0/71 (0%)		1/70 (1.4%)
Ascites	3/71 (4.2%)		2/70 (2.9%)
Colitis	0/71 (0%)		1/70 (1.4%)
Constipation	2/71 (2.8%)		0/70 (0%)
Diarrhoea	1/71 (1.4%)		0/70 (0%)
Dysphagia	4/71 (5.6%)		4/70 (5.7%)
Gastric haemorrhage	1/71 (1.4%)		0/70 (0%)
Gastric perforation	1/71 (1.4%)		0/70 (0%)
Gastric stenosis	1/71 (1.4%)		0/70 (0%)
Gastrointestinal haemorrhage	0/71 (0%)		3/70 (4.3%)
Gastrointestinal obstruction	0/71 (0%)		1/70 (1.4%)
Gastrointestinal perforation	1/71 (1.4%)		0/70 (0%)
Haematemesis	3/71 (4.2%)		0/70 (0%)
Haemorrhoidal haemorrhage	0/71 (0%)		1/70 (1.4%)
Intestinal obstruction	4/71 (5.6%)		0/70 (0%)
Intestinal perforation	1/71 (1.4%)		0/70 (0%)
Large intestinal obstruction	0/71 (0%)		1/70 (1.4%)
Large intestine perforation	0/71 (0%)		2/70 (2.9%)
Melaena	1/71 (1.4%)		1/70 (1.4%)
Nausea	3/71 (4.2%)		2/70 (2.9%)
Obstruction gastric	0/71 (0%)		2/70 (2.9%)
Peritoneal haemorrhage	0/71 (0%)		1/70 (1.4%)
Small intestinal obstruction	3/71 (4.2%)		0/70 (0%)
Upper gastrointestinal haemorrhage	2/71 (2.8%)		0/70 (0%)
Vomiting	3/71 (4.2%)		1/70 (1.4%)
General disorders
Complication associated with device	1/71 (1.4%)		0/70 (0%)
Euthanasia	0/71 (0%)		2/70 (2.9%)
General physical health deterioration	0/71 (0%)		2/70 (2.9%)
Oedema peripheral	0/71 (0%)		1/70 (1.4%)
Pyrexia	2/71 (2.8%)		2/70 (2.9%)
Hepatobiliary disorders
Bile duct obstruction	1/71 (1.4%)		0/70 (0%)
Cholangitis	1/71 (1.4%)		0/70 (0%)
Cholestasis	1/71 (1.4%)		0/70 (0%)
Hepatic function abnormal	0/71 (0%)		1/70 (1.4%)
Hepatitis toxic	1/71 (1.4%)		0/70 (0%)
Hyperbilirubinaemia	1/71 (1.4%)		0/70 (0%)
Jaundice	1/71 (1.4%)		0/70 (0%)
Jaundice cholestatic	0/71 (0%)		1/70 (1.4%)
Infections and infestations
Appendicitis	0/71 (0%)		1/70 (1.4%)
Cellulitis	0/71 (0%)		1/70 (1.4%)
Device related infection	1/71 (1.4%)		1/70 (1.4%)
Infection	1/71 (1.4%)		0/70 (0%)
Liver abscess	1/71 (1.4%)		0/70 (0%)
Lung abscess	1/71 (1.4%)		0/70 (0%)
Pneumonia	2/71 (2.8%)		0/70 (0%)
Postoperative wound infection	0/71 (0%)		1/70 (1.4%)
Sepsis	2/71 (2.8%)		1/70 (1.4%)
Septic shock	1/71 (1.4%)		3/70 (4.3%)
Subcutaneous abscess	1/71 (1.4%)		0/70 (0%)
Subdiaphragmatic abscess	0/71 (0%)		1/70 (1.4%)
Urosepsis	0/71 (0%)		1/70 (1.4%)
Vascular device infection	0/71 (0%)		1/70 (1.4%)
Injury, poisoning and procedural complications
Accidental overdose	0/71 (0%)		1/70 (1.4%)
Investigations
Blood alkaline phosphatase increased	0/71 (0%)		1/70 (1.4%)
Blood bilirubin increased	1/71 (1.4%)		2/70 (2.9%)
Blood creatinine increased	0/71 (0%)		1/70 (1.4%)
Blood magnesium decreased	0/71 (0%)		1/70 (1.4%)
General physical condition abnormal	1/71 (1.4%)		0/70 (0%)
Transaminases increased	1/71 (1.4%)		0/70 (0%)
Metabolism and nutrition disorders
Decreased appetite	2/71 (2.8%)		1/70 (1.4%)
Dehydration	1/71 (1.4%)		1/70 (1.4%)
Hyponatraemia	1/71 (1.4%)		1/70 (1.4%)
Hypophagia	0/71 (0%)		2/70 (2.9%)
Malnutrition	0/71 (0%)		1/70 (1.4%)
Musculoskeletal and connective tissue disorders
Back pain	2/71 (2.8%)		1/70 (1.4%)
Pain in extremity	0/71 (0%)		1/70 (1.4%)
Pathological fracture	1/71 (1.4%)		0/70 (0%)
Polymyalgia rheumatica	1/71 (1.4%)		0/70 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	1/71 (1.4%)		0/70 (0%)
Nervous system disorders
Cerebral haemorrhage	0/71 (0%)		1/70 (1.4%)
Dizziness	0/71 (0%)		1/70 (1.4%)
Hepatic encephalopathy	1/71 (1.4%)		0/70 (0%)
Myasthenia gravis	1/71 (1.4%)		0/70 (0%)
Seizure	0/71 (0%)		1/70 (1.4%)
Psychiatric disorders
Confusional state	0/71 (0%)		1/70 (1.4%)
Renal and urinary disorders
Acute kidney injury	1/71 (1.4%)		1/70 (1.4%)
Renal failure	1/71 (1.4%)		1/70 (1.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/71 (2.8%)		2/70 (2.9%)
Hypoxia	2/71 (2.8%)		0/70 (0%)
Pleural effusion	1/71 (1.4%)		1/70 (1.4%)
Pleurisy	1/71 (1.4%)		0/70 (0%)
Pneumonia aspiration	2/71 (2.8%)		0/70 (0%)
Productive cough	1/71 (1.4%)		0/70 (0%)
Pulmonary embolism	0/71 (0%)		1/70 (1.4%)
Respiratory failure	2/71 (2.8%)		0/70 (0%)
Other (Not Including Serious) Adverse Events
	Andecaliximab + Nivolumab		Nivolumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/71 (93%)		62/70 (88.6%)
Blood and lymphatic system disorders
Anaemia	14/71 (19.7%)		14/70 (20%)
Gastrointestinal disorders
Abdominal distension	4/71 (5.6%)		2/70 (2.9%)
Abdominal pain	11/71 (15.5%)		16/70 (22.9%)
Abdominal pain upper	11/71 (15.5%)		2/70 (2.9%)
Ascites	7/71 (9.9%)		4/70 (5.7%)
Constipation	18/71 (25.4%)		18/70 (25.7%)
Diarrhoea	14/71 (19.7%)		9/70 (12.9%)
Dry mouth	2/71 (2.8%)		5/70 (7.1%)
Dyspepsia	5/71 (7%)		2/70 (2.9%)
Dysphagia	12/71 (16.9%)		8/70 (11.4%)
Gastrooesophageal reflux disease	6/71 (8.5%)		2/70 (2.9%)
Nausea	27/71 (38%)		17/70 (24.3%)
Vomiting	22/71 (31%)		18/70 (25.7%)
General disorders
Asthenia	21/71 (29.6%)		12/70 (17.1%)
Chest pain	1/71 (1.4%)		4/70 (5.7%)
Fatigue	22/71 (31%)		25/70 (35.7%)
Oedema peripheral	6/71 (8.5%)		6/70 (8.6%)
Pyrexia	10/71 (14.1%)		4/70 (5.7%)
Infections and infestations
Nasopharyngitis	4/71 (5.6%)		0/70 (0%)
Oral candidiasis	3/71 (4.2%)		4/70 (5.7%)
Urinary tract infection	7/71 (9.9%)		1/70 (1.4%)
Investigations
Alanine aminotransferase increased	4/71 (5.6%)		4/70 (5.7%)
Aspartate aminotransferase increased	4/71 (5.6%)		4/70 (5.7%)
Weight decreased	5/71 (7%)		7/70 (10%)
Metabolism and nutrition disorders
Decreased appetite	24/71 (33.8%)		20/70 (28.6%)
Dehydration	2/71 (2.8%)		5/70 (7.1%)
Hyperkalaemia	2/71 (2.8%)		4/70 (5.7%)
Hypoalbuminaemia	1/71 (1.4%)		4/70 (5.7%)
Hypokalaemia	5/71 (7%)		7/70 (10%)
Hypomagnesaemia	4/71 (5.6%)		1/70 (1.4%)
Hyponatraemia	2/71 (2.8%)		5/70 (7.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/71 (5.6%)		6/70 (8.6%)
Back pain	11/71 (15.5%)		5/70 (7.1%)
Muscle spasms	0/71 (0%)		4/70 (5.7%)
Myalgia	3/71 (4.2%)		4/70 (5.7%)
Nervous system disorders
Dizziness	6/71 (8.5%)		8/70 (11.4%)
Headache	6/71 (8.5%)		6/70 (8.6%)
Paraesthesia	1/71 (1.4%)		4/70 (5.7%)
Psychiatric disorders
Anxiety	5/71 (7%)		2/70 (2.9%)
Insomnia	3/71 (4.2%)		9/70 (12.9%)
Respiratory, thoracic and mediastinal disorders
Cough	4/71 (5.6%)		8/70 (11.4%)
Dyspnoea	10/71 (14.1%)		9/70 (12.9%)
Skin and subcutaneous tissue disorders
Pruritus	3/71 (4.2%)		6/70 (8.6%)
Vascular disorders
Hypotension	5/71 (7%)		2/70 (2.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years