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

NCT02862535 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: GS-US-296-1884
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

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.

Conditions

Gastric Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• 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).

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

• 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.

  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)

• Cohort 1: Plasma Concentration of Andecaliximab

  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

• PK Parameter: Cmax of Andecaliximab

  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)

• PK Parameter: AUClast of Andecaliximab

  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)

• PK Parameter: AUC0-336h of Andecaliximab

  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)

• Number of Participants With Positive Anti-Andecaliximab Antibodies

  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)

Study Arms (4)

Cohort 1: ADX

EXPERIMENTAL

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

Cohort 2: ADX + S-1 + Cisplatin

EXPERIMENTAL

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; Drug: S-1; Drug: Cisplatin

Cohort 3: ADX + S-1 + Oxaliplatin

EXPERIMENTAL

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; Drug: S-1; Drug: Oxaliplatin

Cohort 4: ADX + Nivolumab

EXPERIMENTAL

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; Drug: Nivolumab

Interventions

Andecaliximab DRUG

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

Also known as: GS-5745

Cohort 1: ADX; Cohort 2: ADX + S-1 + Cisplatin; Cohort 3: ADX + S-1 + Oxaliplatin; Cohort 4: ADX + Nivolumab

S-1 DRUG

Administered orally

Cohort 2: ADX + S-1 + Cisplatin; Cohort 3: ADX + S-1 + Oxaliplatin

Cisplatin DRUG

Administered via IV infusion on Day 8 of every 5 weeks

Cohort 2: ADX + S-1 + Cisplatin

Oxaliplatin DRUG

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

Cohort 3: ADX + S-1 + Oxaliplatin

Nivolumab DRUG

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

Cohort 4: ADX + Nivolumab

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (3)

Unknown Facility

Nagoya, Japan

Location

Unknown Facility

Osaka, Japan

Location

Unknown Facility

Tokyo, Japan

Location

Related Publications (6)

• 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.

  RESULT

• 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.

  RESULT

• 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.

  RESULT

• 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.

  RESULT

• 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.

  PMID: 35773363 DERIVED

• 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.

  PMID: 34992093 DERIVED

MeSH Terms

Interventions

andecaliximab; S 1 (combination); Cisplatin; Oxaliplatin; Nivolumab

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

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

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2016
• First Posted: August 11, 2016
• Study Start: September 20, 2016
• Primary Completion: October 25, 2019
• Study Completion: October 25, 2019
• Last Updated: December 24, 2020
• Results First Posted: December 24, 2020

Record last verified: 2020-11

Locations

JP (3)