Trial Outcomes & Findings for Study to Evaluate the Safety and Tolerability of Andecaliximab as Monotherapy and in Combination With Anti-Cancer Agents in Japanese Participants With Gastric or Gastroesophageal Junction Adenocarcinoma (NCT NCT02862535)

Last Updated: 2020-12-24

Results Overview

TEAEs are any AEs with an onset date of on or after the date that ADX and if applicable, nivolumab was first administered and no later than 30 days after permanent discontinuation of ADX, or if applicable, 5 months after permanent discontinuation of nivolumab (whichever is later).

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

36 participants

Primary outcome timeframe

First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab)

Results posted on

2020-12-24

Participant Flow

Participants were enrolled at study sites in Japan. The first participant was screened on 20 Sep 2016. The last study visit occurred on 25 Oct 2019.

39 participants were screened.

Participant milestones

Participant milestones
Measure	Cohort 1: ADX Participants received andecaliximab (ADX) 800 mg as monotherapy via intravenous (IV) infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.	Cohort 2: ADX + S-1 + Cisplatin Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle in combination with chemotherapy (S-1 administered orally twice daily plus cisplatin administered via IV infusion on Day 8 of every 5 weeks) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. Dose of S-1 and cisplatin was based upon participant condition, investigator discretion, institutional practice or in country label.	Cohort 3: ADX + S-1 + Oxaliplatin Participants received ADX 1200 mg via IV infusion (approximately 30 minutes) every 3 weeks on Day 1 of each 21-day treatment cycle in combination with chemotherapy (S-1 administered at 80 mg/day to 120 mg/day according to the body surface area orally twice daily for first 14 days of 21 day cycle plus oxaliplatin administered via IV infusion at 100 mg/m\^2 over 2 hours on Day 1 of each 21-day cycle) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study.	Cohort 4: ADX + Nivolumab Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks followed by chemotherapy (nivolumab 3 mg/kg via IV infusion \[approximately 60 minutes\] every 2 weeks) on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Overall Study STARTED	9	6	10	11
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	9	6	10	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: ADX Participants received andecaliximab (ADX) 800 mg as monotherapy via intravenous (IV) infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.	Cohort 2: ADX + S-1 + Cisplatin Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle in combination with chemotherapy (S-1 administered orally twice daily plus cisplatin administered via IV infusion on Day 8 of every 5 weeks) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. Dose of S-1 and cisplatin was based upon participant condition, investigator discretion, institutional practice or in country label.	Cohort 3: ADX + S-1 + Oxaliplatin Participants received ADX 1200 mg via IV infusion (approximately 30 minutes) every 3 weeks on Day 1 of each 21-day treatment cycle in combination with chemotherapy (S-1 administered at 80 mg/day to 120 mg/day according to the body surface area orally twice daily for first 14 days of 21 day cycle plus oxaliplatin administered via IV infusion at 100 mg/m\^2 over 2 hours on Day 1 of each 21-day cycle) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study.	Cohort 4: ADX + Nivolumab Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks followed by chemotherapy (nivolumab 3 mg/kg via IV infusion \[approximately 60 minutes\] every 2 weeks) on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Overall Study Death	7	3	2	5
Overall Study Study Terminated by Sponsor	1	3	8	5
Overall Study Enrolled, not Treated	1	0	0	1

Baseline Characteristics

Study to Evaluate the Safety and Tolerability of Andecaliximab as Monotherapy and in Combination With Anti-Cancer Agents in Japanese Participants With Gastric or Gastroesophageal Junction Adenocarcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: ADX n=8 Participants Participants received ADX 800 mg as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.	Cohort 2: ADX+S-1+Cisplatin n=6 Participants Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle in combination with chemotherapy (S-1 administered orally twice daily plus cisplatin administered via IV infusion on Day 8 of every 5 weeks) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. Dose of S-1 and cisplatin was based upon participant condition, investigator discretion, institutional practice or in country label.	Cohort 3: ADX+S-1+Oxaliplatin n=10 Participants Participants received ADX 1200 mg via IV infusion (approximately 30 minutes) every 3 weeks on Day 1 of each 21-day treatment cycle in combination with chemotherapy (S-1 administered at 80 mg/day to 120 mg/day according to the body surface area orally twice daily for first 14 days of 21 day cycle plus oxaliplatin administered via IV infusion at 100 mg/m\^2 over 2 hours on Day 1 of each 21-day cycle) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study.	Cohort 4: ADX+Nivolumab n=10 Participants Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks followed by chemotherapy (nivolumab 3 mg/kg via IV infusion \[approximately 60 minutes\] every 2 weeks) on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.	Total n=34 Participants Total of all reporting groups
Age, Continuous	59 years STANDARD_DEVIATION 14.7 • n=5 Participants	69 years STANDARD_DEVIATION 7.9 • n=7 Participants	56 years STANDARD_DEVIATION 15.1 • n=5 Participants	63 years STANDARD_DEVIATION 11.8 • n=4 Participants	61 years STANDARD_DEVIATION 13.3 • n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	1 Participants n=4 Participants	9 Participants n=21 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	9 Participants n=4 Participants	25 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants	10 Participants n=4 Participants	34 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	8 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants	10 Participants n=4 Participants	34 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab)

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

Outcome measures

Outcome measures
Measure	Cohort 1: ADX n=8 Participants Participants received ADX 800 mg as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.	Cohort 2: ADX + S-1 + Cisplatin n=6 Participants Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle in combination with chemotherapy (S-1 administered orally twice daily plus cisplatin administered via IV infusion on Day 8 of every 5 weeks) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. Dose of S-1 and cisplatin was based upon participant condition, investigator discretion, institutional practice or in country label.	Cohort 3: ADX + S-1 + Oxaliplatin n=10 Participants Participants received ADX 1200 mg via IV infusion (approximately 30 minutes) every 3 weeks on Day 1 of each 21-day treatment cycle in combination with chemotherapy (S-1 administered at 80 mg/day to 120 mg/day according to the body surface area orally twice daily for first 14 days of 21 day cycle plus oxaliplatin administered via IV infusion at 100 mg/m\^2 over 2 hours on Day 1 of each 21-day cycle) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study.	Cohort 4: ADX + Nivolumab n=10 Participants Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks followed by chemotherapy (nivolumab 3 mg/kg via IV infusion \[approximately 60 minutes\] every 2 weeks) on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	100.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants

PRIMARY outcome

Timeframe: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab)

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

Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. If the relevant baseline laboratory value was missing, then any abnormality of at least Grade 1 observed within the specified time frame (first dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab)) was considered treatment-emergent.Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 was used for assigning toxicity grades to laboratory results for analysis.

Outcome measures

Outcome measures
Measure	Cohort 1: ADX n=8 Participants Participants received ADX 800 mg as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.	Cohort 2: ADX + S-1 + Cisplatin n=6 Participants Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle in combination with chemotherapy (S-1 administered orally twice daily plus cisplatin administered via IV infusion on Day 8 of every 5 weeks) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. Dose of S-1 and cisplatin was based upon participant condition, investigator discretion, institutional practice or in country label.	Cohort 3: ADX + S-1 + Oxaliplatin n=10 Participants Participants received ADX 1200 mg via IV infusion (approximately 30 minutes) every 3 weeks on Day 1 of each 21-day treatment cycle in combination with chemotherapy (S-1 administered at 80 mg/day to 120 mg/day according to the body surface area orally twice daily for first 14 days of 21 day cycle plus oxaliplatin administered via IV infusion at 100 mg/m\^2 over 2 hours on Day 1 of each 21-day cycle) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study.	Cohort 4: ADX + Nivolumab n=10 Participants Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks followed by chemotherapy (nivolumab 3 mg/kg via IV infusion \[approximately 60 minutes\] every 2 weeks) on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Any Laboratory abnormalities: Hematology	87.5 percentage of participants	83.3 percentage of participants	90.0 percentage of participants	70.0 percentage of participants
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Any Laboratory abnormalities: Chemistry	100.0 percentage of participants	100.0 percentage of participants	100.0 percentage of participants	80.0 percentage of participants
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Any Laboratory abnormalities: Coagulation	0 percentage of participants	0 percentage of participants	0 percentage of participants	10.0 percentage of participants

SECONDARY outcome

Timeframe: Pre-dose and 30 (±15) min after infusion on C2D1, C3D1, C5D1; EOS (3 years and 1 month); C1 only: 30 (±15) min after infusion on D1; anytime on D2, D4 and D8; Pre-dose and 30 (±15) minutes post infusion on D15

Population: The Pharmacokinetic (PK) Analysis Set included all enrolled participants who took at least 1 dose of study drug and had at least 1 nonmissing postdose concentration value reported by the PK laboratory with available data were analyzed. Due to program discontinuation data were not collected for Cohorts 2, 3, and 4.

Plasma concentration is defined as the measured drug concentration. Blood samples were drawn at pre-dose and 30 (±15) minutes after infusion on Day 1 of Cycles 2, 3, 5; End of study (EOS) (3 years and 1 month); Cycle 1 only: 30 (±15) minutes after infusion on Day 1; anytime on Day 2, 4, and 8; pre-dose and 30 (±15) minutes post infusion on Day 15. The duration of each cycle for Cohort 1, 2, and 4 was 28 days and for Cohort 3 was 21 days. Infusion duration = 30 to 35 minutes. * min=minutes * D=Days * C=Cycle

Outcome measures

Outcome measures
Measure	Cohort 1: ADX n=8 Participants Participants received ADX 800 mg as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.	Cohort 2: ADX + S-1 + Cisplatin Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle in combination with chemotherapy (S-1 administered orally twice daily plus cisplatin administered via IV infusion on Day 8 of every 5 weeks) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. Dose of S-1 and cisplatin was based upon participant condition, investigator discretion, institutional practice or in country label.	Cohort 3: ADX + S-1 + Oxaliplatin Participants received ADX 1200 mg via IV infusion (approximately 30 minutes) every 3 weeks on Day 1 of each 21-day treatment cycle in combination with chemotherapy (S-1 administered at 80 mg/day to 120 mg/day according to the body surface area orally twice daily for first 14 days of 21 day cycle plus oxaliplatin administered via IV infusion at 100 mg/m\^2 over 2 hours on Day 1 of each 21-day cycle) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study.	Cohort 4: ADX + Nivolumab Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks followed by chemotherapy (nivolumab 3 mg/kg via IV infusion \[approximately 60 minutes\] every 2 weeks) on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Cohort 1: Plasma Concentration of Andecaliximab 30 minutes Postdose: Cycle 1 Day 1	262,625.0 nanograms per milliliter Standard Deviation 57410.64	—	—	—
Cohort 1: Plasma Concentration of Andecaliximab Postdose: Cycle 1 Day 2	211,875.0 nanograms per milliliter Standard Deviation 56688.21	—	—	—
Cohort 1: Plasma Concentration of Andecaliximab Postdose: Cycle 1 Day 4	133,100.0 nanograms per milliliter Standard Deviation 57485.39	—	—	—
Cohort 1: Plasma Concentration of Andecaliximab Postdose: Cycle 1 Day 8	90100.0 nanograms per milliliter Standard Deviation 18127.25	—	—	—
Cohort 1: Plasma Concentration of Andecaliximab Predose: Cycle 1 Day 15	54800.0 nanograms per milliliter Standard Deviation 12011.66	—	—	—
Cohort 1: Plasma Concentration of Andecaliximab 30 minutes Postdose: Cycle 1 Day 15	310,971.4 nanograms per milliliter Standard Deviation 128,365.39	—	—	—
Cohort 1: Plasma Concentration of Andecaliximab Predose: Cycle 2 Day 1	122,200.0 nanograms per milliliter Standard Deviation 52872.68	—	—	—
Cohort 1: Plasma Concentration of Andecaliximab 30 minutes Postdose: Cycle 2 Day 1	458,666.7 nanograms per milliliter Standard Deviation 211,613.64	—	—	—
Cohort 1: Plasma Concentration of Andecaliximab Predose: Cycle 3 Day 1	158,000.0 nanograms per milliliter Standard Deviation 16970.56	—	—	—
Cohort 1: Plasma Concentration of Andecaliximab 30 minutes Postdose: Cycle 3 Day 1	349,300.0 nanograms per milliliter Standard Deviation 402,626.60	—	—	—
Cohort 1: Plasma Concentration of Andecaliximab Predose: Cycle 5 Day 1	154,500.0 nanograms per milliliter Standard Deviation 6363.96	—	—	—
Cohort 1: Plasma Concentration of Andecaliximab 30 minutes Postdose: Cycle 5 Day 1	510,500.0 nanograms per milliliter Standard Deviation 136,471.61	—	—	—
Cohort 1: Plasma Concentration of Andecaliximab End of study	61960.0 nanograms per milliliter Standard Deviation 37635.40	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 only: 30 (± 15) minutes after the end of infusion on Day 1; anytime on Days 2, 4, and 8; prior to dosing on Day 15 (Cycle length= 28 days) (infusion duration= 30 to 35 minutes)

Population: Participants in the PK Analysis Set were analyzed. Due to program discontinuation data were not collected for Cohorts 2, 3, and 4.

Cmax is defined as the maximum concentration of drug.

Outcome measures

Outcome measures
Measure	Cohort 1: ADX n=8 Participants Participants received ADX 800 mg as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.	Cohort 2: ADX + S-1 + Cisplatin Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle in combination with chemotherapy (S-1 administered orally twice daily plus cisplatin administered via IV infusion on Day 8 of every 5 weeks) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. Dose of S-1 and cisplatin was based upon participant condition, investigator discretion, institutional practice or in country label.	Cohort 3: ADX + S-1 + Oxaliplatin Participants received ADX 1200 mg via IV infusion (approximately 30 minutes) every 3 weeks on Day 1 of each 21-day treatment cycle in combination with chemotherapy (S-1 administered at 80 mg/day to 120 mg/day according to the body surface area orally twice daily for first 14 days of 21 day cycle plus oxaliplatin administered via IV infusion at 100 mg/m\^2 over 2 hours on Day 1 of each 21-day cycle) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study.	Cohort 4: ADX + Nivolumab Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks followed by chemotherapy (nivolumab 3 mg/kg via IV infusion \[approximately 60 minutes\] every 2 weeks) on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
PK Parameter: Cmax of Andecaliximab	264.0 micrograms per milliliter Standard Deviation 56.42	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 only: 30 (± 15) minutes after the end of infusion on Day 1; anytime on Days 2, 4, and 8; prior to dosing on Day 15 (Cycle length= 28 days) (infusion duration= 30 to 35 minutes)

Population: Participants in the PK Analysis Set were analyzed. Due to program discontinuation data were not collected for Cohorts 2, 3, and 4.

AUClast is defined as the area under the concentration versus time curve to the last measurable concentration of drug from time zero to the last observable concentration.

Outcome measures

Outcome measures
Measure	Cohort 1: ADX n=8 Participants Participants received ADX 800 mg as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.	Cohort 2: ADX + S-1 + Cisplatin Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle in combination with chemotherapy (S-1 administered orally twice daily plus cisplatin administered via IV infusion on Day 8 of every 5 weeks) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. Dose of S-1 and cisplatin was based upon participant condition, investigator discretion, institutional practice or in country label.	Cohort 3: ADX + S-1 + Oxaliplatin Participants received ADX 1200 mg via IV infusion (approximately 30 minutes) every 3 weeks on Day 1 of each 21-day treatment cycle in combination with chemotherapy (S-1 administered at 80 mg/day to 120 mg/day according to the body surface area orally twice daily for first 14 days of 21 day cycle plus oxaliplatin administered via IV infusion at 100 mg/m\^2 over 2 hours on Day 1 of each 21-day cycle) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study.	Cohort 4: ADX + Nivolumab Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks followed by chemotherapy (nivolumab 3 mg/kg via IV infusion \[approximately 60 minutes\] every 2 weeks) on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
PK Parameter: AUClast of Andecaliximab	33500.2 hoursmicrograms per milliliter(hμg/mL) Standard Deviation 8397.01	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 only: 30 (± 15) minutes after the end of infusion on Day 1; anytime on Days 2, 4, and 8; prior to dosing on Day 15 (Cycle length= 28 days) (infusion duration= 30 to 35 minutes)

Population: Participants in the PK Analysis Set with available data were analyzed. Due to program discontinuation data were not collected for Cohorts 2, 3, and 4.

AUC0-336h is defined as the area under the concentration versus time curve from time zero to time 336 hour.

Outcome measures

Outcome measures
Measure	Cohort 1: ADX n=7 Participants Participants received ADX 800 mg as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.	Cohort 2: ADX + S-1 + Cisplatin Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle in combination with chemotherapy (S-1 administered orally twice daily plus cisplatin administered via IV infusion on Day 8 of every 5 weeks) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. Dose of S-1 and cisplatin was based upon participant condition, investigator discretion, institutional practice or in country label.	Cohort 3: ADX + S-1 + Oxaliplatin Participants received ADX 1200 mg via IV infusion (approximately 30 minutes) every 3 weeks on Day 1 of each 21-day treatment cycle in combination with chemotherapy (S-1 administered at 80 mg/day to 120 mg/day according to the body surface area orally twice daily for first 14 days of 21 day cycle plus oxaliplatin administered via IV infusion at 100 mg/m\^2 over 2 hours on Day 1 of each 21-day cycle) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study.	Cohort 4: ADX + Nivolumab Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks followed by chemotherapy (nivolumab 3 mg/kg via IV infusion \[approximately 60 minutes\] every 2 weeks) on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
PK Parameter: AUC0-336h of Andecaliximab	34341.9 h*μg/mL Standard Deviation 8697.66	—	—	—

SECONDARY outcome

Timeframe: Pre-dose on Day 1 of Cycles 1, 2, 3, 5, 7 and every third cycle and anytime at EOT (82.4 weeks) and EOS visit (maximum: 3 years and 1 month) (Each Cycle= 28 days for Cohort 1, 2 and 4; 21 days for Cohort 3)

Population: The Immunogenicity Analysis Set included all participants who took at least 1 dose of study drug and had at least 1 nonmissing postdose antidrug antibody status reported.

Outcome measures

Outcome measures
Measure	Cohort 1: ADX n=8 Participants Participants received ADX 800 mg as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.	Cohort 2: ADX + S-1 + Cisplatin n=6 Participants Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle in combination with chemotherapy (S-1 administered orally twice daily plus cisplatin administered via IV infusion on Day 8 of every 5 weeks) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. Dose of S-1 and cisplatin was based upon participant condition, investigator discretion, institutional practice or in country label.	Cohort 3: ADX + S-1 + Oxaliplatin n=10 Participants Participants received ADX 1200 mg via IV infusion (approximately 30 minutes) every 3 weeks on Day 1 of each 21-day treatment cycle in combination with chemotherapy (S-1 administered at 80 mg/day to 120 mg/day according to the body surface area orally twice daily for first 14 days of 21 day cycle plus oxaliplatin administered via IV infusion at 100 mg/m\^2 over 2 hours on Day 1 of each 21-day cycle) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study.	Cohort 4: ADX + Nivolumab n=10 Participants Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks followed by chemotherapy (nivolumab 3 mg/kg via IV infusion \[approximately 60 minutes\] every 2 weeks) on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Number of Participants With Positive Anti-Andecaliximab Antibodies	0 Participants	0 Participants	0 Participants	0 Participants

Adverse Events

Cohort 1: ADX

Serious events: 2 serious events

Other events: 8 other events

Deaths: 7 deaths

Cohort 2: ADX + S-1 + Cisplatin

Serious events: 2 serious events

Other events: 6 other events

Deaths: 3 deaths

Cohort 3: ADX + S-1 + Oxaliplatin

Serious events: 1 serious events

Other events: 10 other events

Deaths: 2 deaths

Cohort 4: ADX + Nivolumab

Serious events: 5 serious events

Other events: 10 other events

Deaths: 5 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1: ADX n=8 participants at risk Participants received ADX 800 mg as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.	Cohort 2: ADX + S-1 + Cisplatin n=6 participants at risk Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks on Days 1 and 15 of each 28-day treatment cycle in combination with chemotherapy (S-1 administered orally twice daily plus cisplatin administered via IV infusion on Day 8 of every 5 weeks) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug. Dose of S-1 and cisplatin was based upon participant condition, investigator discretion, institutional practice or in country label.	Cohort 3: ADX + S-1 + Oxaliplatin n=10 participants at risk Participants received ADX 1200 mg via IV infusion (approximately 30 minutes) every 3 weeks on Day 1 of each 21-day treatment cycle in combination with chemotherapy (S-1 administered at 80 mg/day to 120 mg/day according to the body surface area orally twice daily for first 14 days of 21 day cycle plus oxaliplatin administered via IV infusion at 100 mg/m\^2 over 2 hours on Day 1 of each 21-day cycle) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study.	Cohort 4: ADX + Nivolumab n=10 participants at risk Participants received ADX 800 mg via IV infusion (approximately 30 minutes) every 2 weeks followed by chemotherapy (nivolumab 3 mg/kg via IV infusion \[approximately 60 minutes\] every 2 weeks) on Days 1 and 15 of each 28-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Blood and lymphatic system disorders Anaemia	0.00% 0/8 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/6 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	10.0% 1/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.
General disorders Malaise	0.00% 0/8 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/6 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	10.0% 1/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.
General disorders Pyrexia	0.00% 0/8 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/6 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	10.0% 1/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.
Hepatobiliary disorders Bile duct stenosis	0.00% 0/8 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/6 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	10.0% 1/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.
Hepatobiliary disorders Cholangitis	0.00% 0/8 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/6 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	10.0% 1/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/8 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	16.7% 1/6 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.
Investigations Blood bilirubin increased	0.00% 0/8 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/6 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	10.0% 1/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.
Metabolism and nutrition disorders Decreased appetite	12.5% 1/8 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	16.7% 1/6 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/8 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	16.7% 1/6 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/8 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/6 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	10.0% 1/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.
Renal and urinary disorders Hydronephrosis	12.5% 1/8 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/6 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.	0.00% 0/10 • Adverse Events: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab) All-Cause Mortality: From study start date up to study completion date (3 years and 1 month) The Safety Analysis Set included all participants who took at least 1 dose of study drug.

Other adverse events

Additional Information

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Gilead Sciences

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Results disclosure agreements

Principal investigator is a sponsor employee 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
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Restriction type: OTHER