Trial Outcomes & Findings for Andecaliximab With mFOLFOX6 as First Line Treatment for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (NCT NCT02545504)

NCT ID: NCT02545504

Last Updated: 2020-05-26

Results Overview

OS was defined as the time interval from the date of randomization to death from any cause.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

432 participants

Primary outcome timeframe

Andecaliximab + mFOLFOX6 median follow-up at the time of final analysis: 19.43 months; Placebo + mFOLFOX6 median follow-up at the time of the final analysis: 19.45 months

Results posted on

2020-05-26

Participant Flow

Participants were enrolled at study sites in Australia, Europe, Chile, Colombia, Peru, Turkey, and the United States. The first participant was screened on 13 October 2015. The last study visit occurred on 15 May 2019.

635 participants were screened.

Participant milestones

Participant milestones
Measure	Andecaliximab + mFOLFOX6 Participants were randomized to receive andecaliximab 800 mg intravenous (IV) plus mFOLFOX6 \[leucovorin (LV)+5-fluorouracil (5-FU) + oxaliplatin (OXA)\] IV as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by andecaliximab 800 mg IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 161.7 weeks.	Placebo + mFOLFOX6 Participants were randomized to receive placebo IV plus mFOLFOX6 (LV+5-FU+OXA) as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by placebo IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 112.3 weeks.
Overall Study STARTED	218	214
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	218	214

Reasons for withdrawal

Reasons for withdrawal
Measure	Andecaliximab + mFOLFOX6 Participants were randomized to receive andecaliximab 800 mg intravenous (IV) plus mFOLFOX6 \[leucovorin (LV)+5-fluorouracil (5-FU) + oxaliplatin (OXA)\] IV as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by andecaliximab 800 mg IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 161.7 weeks.	Placebo + mFOLFOX6 Participants were randomized to receive placebo IV plus mFOLFOX6 (LV+5-FU+OXA) as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by placebo IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 112.3 weeks.
Overall Study Death	174	168
Overall Study Unknown reason	30	32
Overall Study Withdrew consent	9	11
Overall Study Investigator's discretion	3	1
Overall Study Lost to Follow-up	2	2

Baseline Characteristics

Andecaliximab With mFOLFOX6 as First Line Treatment for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Andecaliximab + mFOLFOX6 n=218 Participants Participants were randomized to receive andecaliximab 800 mg IV plus mFOLFOX6 (LV+5-FU+OXA) IV as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by andecaliximab 800 mg IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 161.7 weeks.	Placebo + mFOLFOX6 n=214 Participants Participants were randomized to receive placebo IV plus mFOLFOX6 (LV+5-FU+OXA) as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by placebo IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 112.3 weeks.	Total n=432 Participants Total of all reporting groups
Age, Continuous	60 years STANDARD_DEVIATION 11.9 • n=5 Participants	61 years STANDARD_DEVIATION 11.4 • n=7 Participants	60 years STANDARD_DEVIATION 11.7 • n=5 Participants
Sex: Female, Male Female	50 Participants n=5 Participants	61 Participants n=7 Participants	111 Participants n=5 Participants
Sex: Female, Male Male	168 Participants n=5 Participants	153 Participants n=7 Participants	321 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	186 Participants n=5 Participants	184 Participants n=7 Participants	370 Participants n=5 Participants
Race/Ethnicity, Customized Race · Not Permitted	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	38 Participants n=5 Participants	32 Participants n=7 Participants	70 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	170 Participants n=5 Participants	173 Participants n=7 Participants	343 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Permitted	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Region of Enrollment Colombia	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Romania	15 Participants n=5 Participants	13 Participants n=7 Participants	28 Participants n=5 Participants
Region of Enrollment Hungary	11 Participants n=5 Participants	15 Participants n=7 Participants	26 Participants n=5 Participants
Region of Enrollment United States	47 Participants n=5 Participants	59 Participants n=7 Participants	106 Participants n=5 Participants
Region of Enrollment Czechia	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment United Kingdom	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Spain	27 Participants n=5 Participants	28 Participants n=7 Participants	55 Participants n=5 Participants
Region of Enrollment Turkey	17 Participants n=5 Participants	18 Participants n=7 Participants	35 Participants n=5 Participants
Region of Enrollment Belgium	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Poland	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Region of Enrollment Italy	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Region of Enrollment Australia	13 Participants n=5 Participants	18 Participants n=7 Participants	31 Participants n=5 Participants
Region of Enrollment Chile	15 Participants n=5 Participants	11 Participants n=7 Participants	26 Participants n=5 Participants
Region of Enrollment France	10 Participants n=5 Participants	3 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment Peru	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment Germany	16 Participants n=5 Participants	8 Participants n=7 Participants	24 Participants n=5 Participants
Type of Cancer Gastric	142 Participants n=5 Participants	143 Participants n=7 Participants	285 Participants n=5 Participants
Type of Cancer Gastroesophageal junction	76 Participants n=5 Participants	71 Participants n=7 Participants	147 Participants n=5 Participants

PRIMARY outcome

Timeframe: Andecaliximab + mFOLFOX6 median follow-up at the time of final analysis: 19.43 months; Placebo + mFOLFOX6 median follow-up at the time of the final analysis: 19.45 months

Population: The Intent-to-Treat (ITT) Analysis Set included all randomized participants.

OS was defined as the time interval from the date of randomization to death from any cause.

Outcome measures

Outcome measures
Measure	Andecaliximab + mFOLFOX6 n=218 Participants Participants were randomized to receive andecaliximab 800 mg IV plus mFOLFOX6 (LV+5-FU+OXA) IV as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by andecaliximab 800 mg IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 135.4 weeks at the time of final analysis.	Placebo + mFOLFOX6 n=214 Participants Participants were randomized to receive placebo IV plus mFOLFOX6 (LV+5-FU+OXA) as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by placebo IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 99.7 weeks at the time of final analysis.
Overall Survival (OS)	12.52 months Interval 11.2 to 14.0	11.76 months Interval 10.3 to 13.5

SECONDARY outcome

Timeframe: Andecaliximab + mFOLFOX6 median follow-up at the time of the final analysis: 18.64 months; Placebo + mFOLFOX6 median follow-up at the time of the final analysis: 18.74 months

Population: Participants in the ITT Analysis Set were analyzed.

PFS was defined as the interval of time from the date of randomization to the earlier of the first documentation of definitive disease progression or death from any cause.

Outcome measures

Outcome measures
Measure	Andecaliximab + mFOLFOX6 n=218 Participants Participants were randomized to receive andecaliximab 800 mg IV plus mFOLFOX6 (LV+5-FU+OXA) IV as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by andecaliximab 800 mg IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 135.4 weeks at the time of final analysis.	Placebo + mFOLFOX6 n=214 Participants Participants were randomized to receive placebo IV plus mFOLFOX6 (LV+5-FU+OXA) as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by placebo IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 99.7 weeks at the time of final analysis.
Progression-free Survival (PFS)	7.46 months Interval 7.29 to 8.41	7.06 months Interval 5.52 to 7.46

SECONDARY outcome

Timeframe: Up to 135.4 weeks at the time of final analysis

Population: Participants in the ITT Analysis Set were analyzed.

ORR was defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. 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.

Outcome measures

Outcome measures
Measure	Andecaliximab + mFOLFOX6 n=218 Participants Participants were randomized to receive andecaliximab 800 mg IV plus mFOLFOX6 (LV+5-FU+OXA) IV as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by andecaliximab 800 mg IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 135.4 weeks at the time of final analysis.	Placebo + mFOLFOX6 n=214 Participants Participants were randomized to receive placebo IV plus mFOLFOX6 (LV+5-FU+OXA) as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by placebo IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 99.7 weeks at the time of final analysis.
Objective Response Rate (ORR)	50.5 percentage of participants Interval 43.6 to 57.3	41.1 percentage of participants Interval 34.5 to 48.0

SECONDARY outcome

Timeframe: First dose date up to the last dose date (maximum:161.7 weeks) plus 30 to 55 days

Population: The Safety Analysis Set included all participants who received at least one dose of andecaliximab/placebo.

An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal product, which does not necessarily have a causal relationship with the treatment. TEAEs are events in a given study period that meet any of the following criteria: Any AE with onset date of on or after andecalizimab/placebo start date and no later than 30 days after permanent discontinuation of all study treatment (andecaliximab/placebo and chemotherapy) or Any AEs with onset date of on or after the andecaliximab/placebo start date and no later than 55 days after permanent discontinuation of andecaliximab/placebo or AEs leading to discontinuation of andecaliximab/placebo.

Outcome measures

Outcome measures
Measure	Andecaliximab + mFOLFOX6 n=216 Participants Participants were randomized to receive andecaliximab 800 mg IV plus mFOLFOX6 (LV+5-FU+OXA) IV as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by andecaliximab 800 mg IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 135.4 weeks at the time of final analysis.	Placebo + mFOLFOX6 n=210 Participants Participants were randomized to receive placebo IV plus mFOLFOX6 (LV+5-FU+OXA) as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by placebo IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 99.7 weeks at the time of final analysis.
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)	99.1 percentage of participants	99.5 percentage of participants

SECONDARY outcome

Timeframe: First dose date up to the last dose date (maximum: 161.7 weeks) plus 30 to 55 days

Population: Participants in the Safety Analysis Set were analyzed.

Treatment-emergent 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 post-baseline time point, up to 30 days after the last dose of all study treatment, or 55 days after the last dose of andecaliximab/placebo for participants who permanently discontinued all study treatments. If the relevant baseline laboratory value is missing, then any abnormality of at least Grade 1 was considered treatment-emergent.

Outcome measures

Outcome measures
Measure	Andecaliximab + mFOLFOX6 n=216 Participants Participants were randomized to receive andecaliximab 800 mg IV plus mFOLFOX6 (LV+5-FU+OXA) IV as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by andecaliximab 800 mg IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 135.4 weeks at the time of final analysis.	Placebo + mFOLFOX6 n=210 Participants Participants were randomized to receive placebo IV plus mFOLFOX6 (LV+5-FU+OXA) as per standard of care on Days 1 and 15 of each 28-day treatment cycle during Cycles 1-6, followed by placebo IV plus LV+5-FU on Days 1 and 15 during subsequent cycles until disease progression, unacceptable toxicity, consent withdrawal, or the participant's refusal of treatment for up to 99.7 weeks at the time of final analysis.
Percentage of Participants With Clinically Relevant Treatment-emergent Laboratory Abnormalities Hematology	94.4 percentage of participants	89.5 percentage of participants
Percentage of Participants With Clinically Relevant Treatment-emergent Laboratory Abnormalities Serum Chemistry	91.7 percentage of participants	92.9 percentage of participants
Percentage of Participants With Clinically Relevant Treatment-emergent Laboratory Abnormalities Coagulation	7.4 percentage of participants	3.3 percentage of participants

Adverse Events

Andecaliximab + mFOLFOX6

Serious events: 103 serious events

Other events: 209 other events

Deaths: 174 deaths

Placebo + mFOLFOX6

Serious events: 108 serious events

Other events: 203 other events

Deaths: 168 deaths

Serious adverse events

Other adverse events

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

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
Publication restrictions are in place

Restriction type: OTHER