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Gastric AdenocarcinomaPhase 1NCT02862535

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

A Phase 1 study testing Andecaliximab, S-1 and Cisplatin in people with Gastric Adenocarcinoma, run by Gilead Sciences at 3 sites in Japan.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Gastric Adenocarcinoma
What is being tested?
Andecaliximab, S-1 and Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
3 sitesJapan
Study dates
20 Sep 2016to 25 Oct 2019
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

3 sites in 1 country.

Japan3 sites

  • Study site

    Nagoya

  • Study site

    Osaka

  • Study site

    Tokyo

Other trials in Japan

About this study

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

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.

Being tested
Andecaliximab, S-1, Cisplatin, Oxaliplatin, Nivolumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AndecaliximabDrug

    Also called GS-5745

    Administered via intravenous (IV) infusion (approximately 30 minutes)

  • S-1Drug

    Administered orally

  • CisplatinDrug

    Administered via IV infusion on Day 8 of every 5 weeks

  • OxaliplatinDrug

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

  • NivolumabDrug

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

Study groups in NCT02862535
Study groupRoleWhat they receive
Cohort 1: ADXExperimentalParticipants 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.
Receives: Drug: Andecaliximab
Cohort 2: ADX + S-1 + CisplatinExperimentalParticipants 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.
Receives: Drug: Andecaliximab; Drug: S-1; Drug: Cisplatin
Cohort 3: ADX + S-1 + OxaliplatinExperimentalParticipants 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.
Receives: Drug: Andecaliximab; Drug: S-1; Drug: Oxaliplatin
Cohort 4: ADX + NivolumabExperimentalParticipants 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.
Receives: Drug: Andecaliximab; Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)

    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).

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

  2. Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities

    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.

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

Secondary outcomes (5)

  1. Cohort 1: Plasma Concentration of Andecaliximab

    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

    Measured: 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

  2. PK Parameter: Cmax of Andecaliximab

    Cmax is defined as the maximum concentration of drug.

    Measured: 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)

  3. PK Parameter: AUClast of Andecaliximab

    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.

    Measured: 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)

  4. PK Parameter: AUC0-336h of Andecaliximab

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

    Measured: 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)

  5. Number of Participants With Positive Anti-Andecaliximab Antibodies

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Aug 2016 (estimated)
  2. Study start20 Sep 2016
  3. Primary completion25 Oct 2019
  4. Study completion25 Oct 2019

Why it stopped: Study was terminated due to sponsor's decision to not pursue further development of andecaliximab in oncology

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02862535
Sponsor's protocol ID
GS-US-296-1884
Status last verified
Nov 2020
First submitted
8 Aug 2016
Last updated
24 Dec 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

  • Ooki A, Satoh T, Muro K, Takashima A, Kadowaki S, Sakai D, Ichimura T, Mitani S, Kudo T, Chin K, Kitano S, Thai D, Zavodovskaya M, Liu J, Boku N, Yamaguchi K. A phase 1b study of andecaliximab in combination with S-1 plus platinum in Japanese patients with gastric adenocarcinoma. Sci Rep. 2022 Jun 30;12(1):11007. doi: 10.1038/s41598-022-13801-1.

    PubMed 35773363

  • Yoshikawa AK, Yamaguchi K, Muro K, Takashima A, Ichimura T, Sakai D, Kadowaki S, Chin K, Kudo T, Mitani S, Kitano S, Thai D, Zavodovskaya M, Liu J, Boku N, Satoh T. Safety and tolerability of andecaliximab as monotherapy and in combination with an anti-PD-1 antibody in Japanese patients with gastric or gastroesophageal junction adenocarcinoma: a phase 1b study. J Immunother Cancer. 2022 Jan;10(1):e003518. doi: 10.1136/jitc-2021-003518.

    PubMed 34992093

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Andecaliximab, S-1 and Cisplatin in people with Gastric Adenocarcinoma, run by Gilead Sciences at 3 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02862535, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2020.

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