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Andecaliximab

Phase 3

Gastric Adenocarcinoma | Small molecule | Oncology |Gilead Sciences, Inc.|Last Updated: Feb 1, 2021

Success Probability

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Trial Design

RandomizedDouble-BlindACTIVE_CONTROLLEDDMC
Total Trials2
Total Enrollment576

FDA Designations

No designations recorded

Clinical trial landscape

Andecaliximab · 5 trials · 9 indications

Phase 3 1Phase 2 1Phase 1 3
NCT02545504Andecaliximab With mFOLFOX6 as First Line Treatment for Advanced Gastric or Gastroesophageal Junction AdenocarcinomaGastric Adenocarcinoma
COMPLETED432 Analytics
PHASE3COMPLETED
Andecaliximab With mFOLFOX6 as First Line Treatment for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Gastric AdenocarcinomaUnlock trial analytics

Study Endpoints

Primary Endpoints

Overall Survival (OS)
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

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

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.

Percentage of Participants Experiencing Treatment-Emergent Adverse Events
First dose date up to Day 29 plus 30 days
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
First dose date up to Day 29 plus 30 days

A treatment-emergent laboratory abnormality was defined as an increase of at least 1 abnormality grade from baseline and occurring after the first dose of study drug and within 30 days after last study drug administration. The severity of laboratory abnormalities was assessed as Grade 0, 1 (mild), 2 (moderate), 3 (severe), or 4 (potentially life threatening) using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. The most severe graded abnormality from all tests was counted for each participant.

Percentage of Participants Who Developed Anti-andecaliximab Antibodies
Day 43

The presence of anti-andecaliximab antibodies in serum samples was determined using an electrochemiluminescent (ECL) assay that detects antibodies that bind to andecaliximab.

Percentage of Participants Experiencing Laboratory Abnormalities
Part A: First dose date up to 32 weeks plus 30 days; Part B: First dose date up to 181 weeks plus 30 days

Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. Participants with any laboratory abnormality were reported.

Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events (TEAEs) (SAD/MAD)
SAD Cohorts: First dose date (Day 1) plus 30 days, MAD/Adaptive MAD Cohort: First dose date up to last dose date (Maximum: Day 29) plus 30 days

TEAEs are any AEs with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug.

Pharmacokinetic (PK) Parameter: Cmax (SAD)
Predose and 1, 2, and 6 hours postdose on Day 1; Days 2, 3, 8, 15, 29, and 43

Cmax is defined as the maximum concentration of drug.

PK Parameter: Cmax (MAD)
MAD Cohorts: Predose and 1, 2, and 6 hours postdose on Days 1 and 29, Predose on Days 8 and 36; Adaptive MAD Cohort: Predose and 6 hours postdose on Days 1, and 29, Predose on Days 8 and 36

Cmax is defined as the maximum concentration of drug over the dosing interval. Data for Day 1 was based on the data collected from Day 1 through Day 8. Data for Day 29 was based on the data collected from Day 29 through Day 36.

PK Parameter: Ctau (MAD)
MAD Cohorts: Predose and 1, 2, and 6 hours postdose on Day 29; Predose on Day 36; Adaptive MAD Cohort: Predose and 6 hours postdose on Day 29; Predose on Day 36

Ctau is defined as the observed drug concentration at the end of the dosing interval.

PK Parameter: AUCinf (SAD)
Predose and 1, 2, and 6 hours postdose on Day 1; Days 2, 3, 8, 15, 29, and 43

AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time.

PK Parameter: AUCtau (MAD)
MAD Cohorts: Predose and 1, 2, and 6 hours postdose on Days 1 and 29; Predose on Days 8 and 36; Adaptive MAD Cohort: Predose and 6 hours postdose on Days 1, and 29; Predose on Days 8 and 36

AUCtau is defined as the area under the plasma concentration versus time curve over the dosing interval. Data for Day 1 was based on the data collected from Day 1 through Day 8. Data for Day 29 was based on the data collected from Day 29 through Day 36.

PK Parameter: AUClast (SAD)
Predose and 1, 2, and 6 hours postdose on Day 1; Days 2, 3, 8, 15, 29, and 43

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

Secondary Endpoints

Progression-free Survival (PFS)
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
Objective Response Rate (ORR)
Up to 135.4 weeks at the time of final analysis
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
First dose date up to the last dose date (maximum:161.7 weeks) plus 30 to 55 days
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
AndecaliximabEXPERIMENTALAndecaliximab plus mFOLFOX6 (LV+5-FU+OXA) during Cycles 1-6, followed by andecaliximab plus LV+5-FU during subsequent cycles
PlaceboPLACEBO_COMPARATORPlacebo plus mFOLFOX6 (LV+5-FU+OXA) during Cycles 1-6, followed by placebo plus LV+5-FU during subsequent cycles
Andecaliximab + NivolumabEXPERIMENTALAndecaliximab 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).
NivolumabACTIVE_COMPARATORNivolumab 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).
Placebo to match andecaliximabPLACEBO_COMPARATORParticipants will receive placebo to match andecaliximab every 2 weeks for a total of 3 infusions.
Part A: ADX 200 mgEXPERIMENTALParticipants with advanced solid tumors who fail or are intolerant to standard therapy or for whom no standard therapy exists, will receive 200 mg ADX as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Part A: ADX 600 mgEXPERIMENTALParticipants with advanced solid tumors who fail or are intolerant to standard therapy or for whom no standard therapy exists, will receive 600 mg ADX as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Part A: ADX 1800 mgEXPERIMENTALParticipants with advanced solid tumors who fail or are intolerant to standard therapy or for whom no standard therapy exists, will receive 1800 mg ADX as monotherapy via IV infusion (approximately 30 minutes) every 2 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug
Part B: PAC, ADX 800 mgEXPERIMENTALParticipants with PAC will receive ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (gemcitabine and nab paclitaxel, on Days 1, 8, and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Part B: LAC, ADX 1200 mgEXPERIMENTALParticipants with lung adenocarcinoma (LAC) will receive ADX 1200 mg every 3 weeks via IV infusion in addition to the 21-day cycle chemotherapy (carboplatin and pemetrexed, on Day 1) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Part B: LSC, ADX 1200 mgEXPERIMENTALParticipants with lung squamous cell carcinoma (LSC) will receive ADX 1200 mg every 3 weeks via IV infusion in addition to the 21-day cycle chemotherapy (carboplatin and paclitaxel, on Day 1) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Part B: EGC, ADX 800 mgEXPERIMENTALParticipants with esophagogastric adenocarcinoma (EGC) will receive ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (leucovorin+oxaliplatin+5-fluorouracil {5-FU} \[mFOLFOX6\], on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Part B: FL CRC, ADX 800 mg+BEV 5 mg/kgEXPERIMENTALParticipants with colorectal cancer (CRC) will receive first-line (FL) treatment with ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (mFOLFOX6 and bevacizumab 5 mg/kg, on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Part B: FL CRC, ADX 800 mg+BEV 10 mg/kgEXPERIMENTALParticipants with CRC will receive FL treatment with ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (mFOLFOX6 and bevacizumab 10 mg/kg, on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Part B: SL CRC, ADX 800 mg+BEV 5 mg/kgEXPERIMENTALParticipants with CRC will receive second-line (SL) treatment with ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (leucovorin+irinotecan+5-FU \[FOLFIRI\] and bevacizumab 5 mg/kg, on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Part B: SL CRC, ADX 800 mg+BEV 10 mg/kgEXPERIMENTALParticipants with CRC will receive SL treatment with ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (FOLFIRI and bevacizumab 10 mg/kg, on Days 1 and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Part B: BRCA, ADX 800 mgEXPERIMENTALParticipants with breast cancer (BRCA) will receive ADX 800 mg every 2 weeks via IV infusion in addition to the 28-day cycle chemotherapy (paclitaxel, on Days 1, 8, and 15) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Andecaliximab 0.3 mg/kg IV single ascending dose (SAD)EXPERIMENTALParticipants will receive andecaliximab 0.3 milligrams per kilogram (mg/kg) on Day 1.
Andecaliximab 1.0 mg/kg IV (SAD)EXPERIMENTALParticipants will receive andecaliximab 1.0 mg/kg on Day 1.
Andecaliximab 2.5 mg/kg IV (SAD)EXPERIMENTALParticipants will receive andecaliximab 2.5 mg/kg on Day 1.
Andecaliximab 5.0 mg/kg IV (SAD)EXPERIMENTALParticipants will receive andecaliximab 5.0 mg/kg on Day 1.
Placebo Pooled (SAD)PLACEBO_COMPARATORParticipants will receive placebo on Day 1.
Andecaliximab 0.3 mg/kg IV multiple ascending doses (MAD)EXPERIMENTALParticipants will receive andecaliximab 0.3 mg/kg on Days 1, 15, and 29.
Andecaliximab 1.0 mg/kg IV (MAD)EXPERIMENTALParticipants will receive andecaliximab 1.0 mg/kg on Days 1, 15, and 29.
Andecaliximab 2.5 mg/kg IV (MAD)EXPERIMENTALParticipants will receive andecaliximab 2.5 mg/kg on Days 1, 15, and 29.
Andecaliximab 5.0 mg/kg IV (MAD)EXPERIMENTALParticipants will receive andecaliximab 5.0 mg/kg on Days 1, 15, and 29.
Andecaliximab 150 mg SC (Adaptive MAD)EXPERIMENTALParticipants will receive andecaliximab 150 mg on Days 1, 8, 15, 22, and 29.
Placebo Pooled (MAD)PLACEBO_COMPARATORParticipants will receive placebo on Days 1, 15, and 29.

Interventions

NameTypeDescription
AndecaliximabDRUG800 mg administered intravenously on Days 1 and 15 of each 28-day treatment cycle
PlaceboDRUGAdministered intravenously on Days 1 and 15 of each treatment cycle
LeucovorinDRUGAdministered intravenously per standard of care on Days 1 and 15 of each treatment cycle
5-fluorouracilDRUGAdministered intravenously per standard of care on Days 1 and 15 of each treatment cycle
OxaliplatinDRUGAdministered intravenously per standard of care on Days 1 and 15 of each treatment cycle
NivolumabDRUG3 mg/kg administered via IV infusion
Placebo to match AndecaliximabDRUGPlacebo to match andecaliximab administered intravenously
GemcitabineDRUGAdministered intravenously on Days 1, 8, and 15 of each 28-day treatment cycle
Nab-paclitaxelDRUGAdministered intravenously on Days 1, 8, and 15 of each 28-day treatment cycle
CarboplatinDRUGAdministered intravenously on Day 1 of each 21-day treatment cycle
PemetrexedDRUGAdministered intravenously on Day 1 of each 21-day treatment cycle
5-FUDRUGAdministered intravenously on Days 1 and 15 of each 28-day treatment cycle
BevacizumabDRUGAdministered intravenously on Days 1 and 15 of each 28-day treatment cycle
IrinotecanDRUGAdministered intravenously on Days 1 and 15 of each 28-day treatment cycle
PaclitaxelDRUGAdministered intravenously on Days 1, 8 and 15 of each 28-day treatment cycle (Breast cancer) or on Day 1 of each 21-day treatment cycle (NSCLC)
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites134

Key Inclusion Criteria: * Adults with histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction that is inoperable, locally advanced or metastatic and not amenable to curative therapy * Adequate hematologic, liver, coagulation and kidney function * Eastern Cooperative Onco...

Countries:United StatesAustraliaBelgiumChileColombiaCzechiaFranceGermanyHungaryItalyPeruPolandRomaniaSpainTurkey (Türkiye)United KingdomCanadaMoldovaNetherlands
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Frequently asked questions about Andecaliximab

What is Andecaliximab used for?

Andecaliximab is an investigational drug being studied for ulcerative colitis, chronic obstructive pulmonary disease, pancreatic cancer, and gastric adenocarcinoma. It has been evaluated in clinical trials for these conditions, though it remains in clinical development and is not approved for any use.

Who makes Andecaliximab?

Andecaliximab is being developed by Gilead Sciences, Inc., which trades on the NASDAQ under the ticker GILD. The company has sponsored clinical trials of the drug across multiple indications.

What phase is Andecaliximab in?

Andecaliximab has completed Phase 1, Phase 2, and Phase 3 clinical trials. Its development program includes early-stage safety studies and later-stage efficacy trials in gastric adenocarcinoma. The drug is investigational and has not been approved by regulatory authorities.

What clinical trials is Andecaliximab in?

Andecaliximab has been studied in several completed trials, including NCT01831427 for ulcerative colitis, NCT02077465 for chronic obstructive pulmonary disease, NCT02545504 for gastric adenocarcinoma, and NCT02864381 for gastric and gastroesophageal junction adenocarcinoma. These trials have all been completed.

Is Andecaliximab the same as GS-5745?

Yes, Andecaliximab is also known as GS-5745. One clinical trial, NCT01831427, refers to the drug as GS-5745 in its title, confirming that the two names refer to the same investigational compound.

How does Andecaliximab work?

Andecaliximab is a small molecule being developed by Gilead Sciences. Its specific molecular target has not been disclosed in the available clinical trial information, so its mechanism of action is not described here.