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

NCT ID: NCT02862535

Last Updated: 2020-12-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-20
• Study Completion Date: 2019-10-25

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

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

S-1

Intervention Type: DRUG

Administered orally

Cisplatin

Intervention Type: DRUG

Administered via IV infusion on Day 8 of every 5 weeks

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.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

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

S-1

Intervention Type: DRUG

Administered orally

Oxaliplatin

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Andecaliximab

Intervention Type: DRUG

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

Nivolumab

Intervention Type: DRUG

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

Interventions

Andecaliximab

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

Intervention Type: DRUG

S-1

Administered orally

Intervention Type: DRUG

Cisplatin

Administered via IV infusion on Day 8 of every 5 weeks

Intervention Type: DRUG

Oxaliplatin

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

Intervention Type: DRUG

Nivolumab

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

Intervention Type: DRUG

Other Intervention Names

GS-5745

Eligibility Criteria

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

• 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.

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)

• 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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Nagoya, , Japan

Osaka, , Japan

Tokyo, , Japan

Countries

Japan

References

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.

Reference Type: 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.

Reference Type: 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.

Reference Type: 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.

Reference Type: 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.

Reference Type: DERIVED

PMID: 35773363 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34992093 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GS-US-296-1884

Identifier Type: -

Identifier Source: org_study_id