Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02862535
Recruitment Status : Terminated (Study was terminated due to sponsor's decision to not pursue further development of andecaliximab in oncology)
First Posted : August 11, 2016
Results First Posted : December 24, 2020
Last Update Posted : December 24, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:
The primary objective of this study is to characterize the safety and tolerability of andecaliximab as monotherapy and in combination with anti-cancer agents in Japanese participants with inoperable advanced or recurrent gastric or recurrent gastroesophageal junction (GEJ) adenocarcinoma.

Condition or disease Intervention/treatment Phase
Gastric Adenocarcinoma Drug: Andecaliximab Drug: S-1 Drug: Cisplatin Drug: Oxaliplatin Drug: Nivolumab Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Study to Evaluate the Safety and Tolerability of Andecaliximab (GS-5745) as Monotherapy and in Combination With Anti-Cancer Agents in Japanese Subjects With Gastric or Gastroesophageal Junction Adenocarcinoma
Actual Study Start Date : September 20, 2016
Actual Primary Completion Date : October 25, 2019
Actual Study Completion Date : October 25, 2019

Arm Intervention/treatment
Experimental: Cohort 1: ADX
Participants will receive andecaliximab (ADX) 800 mg 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.
Drug: Andecaliximab
Administered via intravenous (IV) infusion (approximately 30 minutes)
Other Name: GS-5745

Experimental: Cohort 2: ADX + S-1 + Cisplatin
Participants will receive ADX 800 mg every 2 weeks on Days 1 and 15 of each 28-day treatment cycle in combination with S-1 orally twice daily plus cisplatin chemotherapy (dosage and regimen will be based on participant condition, investigator discretion, institutional practice, and/or the in-country label) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study drug.
Drug: Andecaliximab
Administered via intravenous (IV) infusion (approximately 30 minutes)
Other Name: GS-5745

Drug: S-1
Administered orally

Drug: Cisplatin
Administered via IV infusion on Day 8 of every 5 weeks

Experimental: Cohort 3: ADX + S-1 + Oxaliplatin
Participants will receive ADX 1200 mg every 3 weeks on Day 1 of each 21-day treatment cycle in combination with chemotherapy (S-1 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 100 mg/m^2) until disease progression, unacceptable toxicity, withdrawal of consent, or other reasons prespecified in the protocol for discontinuation of study.
Drug: Andecaliximab
Administered via intravenous (IV) infusion (approximately 30 minutes)
Other Name: GS-5745

Drug: S-1
Administered orally

Drug: Oxaliplatin
Administered via IV infusion for over 2 hours on Day 1 of each 21-day cycle

Experimental: Cohort 4: ADX + Nivolumab
Participants will receive ADX 800 mg every 2 weeks followed by chemotherapy (nivolumab 3 mg/kg) 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.
Drug: Andecaliximab
Administered via intravenous (IV) infusion (approximately 30 minutes)
Other Name: GS-5745

Drug: Nivolumab
Administered via IV infusion (approximately 60 minutes) every 2 weeks




Primary Outcome Measures :
  1. Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) [ 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) ]
    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).

  2. Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities [ 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) ]
    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.


Secondary Outcome Measures :
  1. Cohort 1: Plasma Concentration of Andecaliximab [ Time Frame: 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 ]

    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

  2. PK Parameter: Cmax of Andecaliximab [ Time Frame: 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) ]
    Cmax is defined as the maximum concentration of drug.

  3. PK Parameter: AUClast of Andecaliximab [ Time Frame: 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) ]
    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.

  4. PK Parameter: AUC0-336h of Andecaliximab [ Time Frame: 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) ]
    AUC0-336h is defined as the area under the concentration versus time curve from time zero to time 336 hour.

  5. Number of Participants With Positive Anti-Andecaliximab Antibodies [ Time Frame: 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) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Must have been born in Japan and must not have lived outside of Japan for a period > 1 year in the 5 years prior to Day 1
  • Must be able to trace their maternal and paternal ancestry of parents and grandparents as ethnically Japanese
  • Histologically confirmed inoperable advanced gastric adenocarcinoma (including adenocarcinoma of the GEJ) or relapsed gastric adenocarcinoma
  • Cohorts 1, 2, and 3: Human Epidermal Growth Factor Receptor 2 (HER2)-negative tumor (primary tumor or metastatic lesion). Enrollment in Cohort 4 is not restricted by HER2 status (adults with HER2-positive, HER2-negative, or unknown HER2 status are eligible)
  • Cohort 1: Prior antitumor therapy or cytotoxic chemotherapy is acceptable. Individuals who are not eligible to receive standard treatments should enroll on the study.
  • Cohorts 2 and 3: Prior antitumor therapy or cytotoxic chemotherapy for metastatic disease is not acceptable. Individuals must be chemo-naive in the metastatic setting
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
  • Adequate baseline organ function (within 28 days prior to Day 1)
  • Coagulation: International Normalized Ratio (INR) ≤ 1.5 (unless receiving anticoagulation therapy)
  • For females of childbearing potential, willingness to use a protocol-recommended method of contraception from the screening visit throughout the study treatment period and for defined periods following the last dose of andecaliximab and/or anti-cancer agent(s)
  • For males of childbearing potential having intercourse with females of childbearing potential, willingness to use a protocol-recommended method of contraception from the start of andecaliximab, throughout the study treatment period, and for protocol defined periods following the last dose of andecaliximab and/or anti-cancer agent(s)
  • Willingness to comply with scheduled visits, drug administration plan, imaging studies, laboratory tests, other study procedures, and study restrictions
  • In addition to the applicable criteria above, participants in Cohort 4 must meet additional inclusion criteria to be eligible for participation in this study:

    • Measurable gastric or GEJ adenocarcinoma
    • Must have progressed on at least 1 prior systemic therapy or line of treatment for unresectable/metastatic disease.
    • Activated partial thromboplastin (aPTT) ≤ 1.5 times the upper limit of normal
    • Thyroid function tests should be within normal limits.

Key Exclusion Criteria:

  • History or evidence of a clinically significant disorder, condition, or disease that, in the opinion of the investigator and medical monitor would pose a risk to participant safety or interfere with the study evaluations, procedures, or completion
  • Pregnant or lactating. Enrollment of lactating females after discontinuation of breastfeeding is not acceptable.
  • Individuals with known central nervous system (CNS) metastases, unless metastases are treated and stable and the individual does not require systemic steroids
  • Radiotherapy within 28 days of Day 1
  • Myocardial infarction, symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months of Day 1
  • History of major surgery within 28 days of Day 1
  • Serious systemic fungal, bacterial, viral, or other infection that is not controlled or requires IV antibiotics
  • Individuals known to be positive for human immunodeficiency virus (HIV), hepatitis C infection (per local standard diagnostic criteria), or acute or chronic hepatitis B infection (per local standard diagnostic criteria)
  • In addition to the applicable criteria above, participants in Cohort 4 who meet any of the following exclusion criteria will not be enrolled in this study

    • Have received only neoadjuvant or adjuvant therapy for gastric adenocarcinoma
    • Prior treatment with anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) agents, anti-programmed cell death protein 1 (anti PD-1) or anti-programmed cell death ligand 1 (anti-PD-L1) agents, anti-programmed cell death ligand 2 (anti-PD-L2) agents, anti-matrix metalloprotease (anti-MMP) agents, or other immunomodulatory therapies

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02862535


Locations
Layout table for location information
Japan
Nagoya, Japan
Osaka, Japan
Tokyo, Japan
Sponsors and Collaborators
Gilead Sciences
Investigators
Layout table for investigator information
Study Director: Gilead Study Director Gilead Sciences
  Study Documents (Full-Text)

Documents provided by Gilead Sciences:
Study Protocol  [PDF] July 14, 2017
Statistical Analysis Plan  [PDF] December 2, 2019

Publications of Results:
Yamaguchi K, Satoh T, Muro K, Takashima A, Ichimura T, et al. Phase 1b Study of Andecaliximab as Monotherapy and in Combination With Nivolumab in Japanese Patients With Gastric or GEJ Adenoracinoma [Poster L9]. Presented at ASCO GI 2019 Gastrointestinal Cancers Symposium: Jan 17-19, 2019, San Francisco, CA, USA.
Muro K, Yamaguchi K, Satoh T, Kadowaki S, Ichimura T, et al. Phase 1b Study of Andecaliximab in Combination With S-1 + Platinum Chemotherapy in Japanese Patients With Advanced Gastric or GEJ Adenocarcinoma [Poster G3]. Presented at ASCO GI 2019 Gastrointestinal Cancers Symposium: Jan 17-19, 2019, San Francisco, CA, USA.
Muro K, Satoh T, Yamaguchi K, Kadowaki S, Sakai D, et al. Phase 1b Study of Andecaliximab (ADX) as Monotherapy and in Combination With Nivolumab (nivo) in Japanese Subjects With Gastric or GEJ Adenocarcinoma. Presented at the Japanese Gastric Cancer Association: Feb 28, 2019.
Satoh T, Yamaguchi K, Muro K, Sakai D, Ichimura T, et al. Phase 1b Study of Andecaliximab (GS-5745, ADX) in Combination With S-1 + Platinum Chemotherapy in Japanese Subjects With Advanced Gastric or GEJ Adenocarcinoma. Presented at the Japanese Gastric Cancer Association: Feb 28, 2019.

Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02862535    
Other Study ID Numbers: GS-US-296-1884
First Posted: August 11, 2016    Key Record Dates
Results First Posted: December 24, 2020
Last Update Posted: December 24, 2020
Last Verified: November 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
Layout table for MeSH terms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Cisplatin
Oxaliplatin
Nivolumab
Antineoplastic Agents
Antineoplastic Agents, Immunological