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

Gilead Sciences

Status and phase: Terminated; Phase 1

Conditions: Gastric Adenocarcinoma

Treatments: Drug: Cisplatin; Drug: Oxaliplatin; Drug: S-1; Drug: Andecaliximab; Drug: Nivolumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02862535

GS-US-296-1884

Details and patient eligibility

About

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.

Enrollment: 36 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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36 participants in 4 patient groups

Cohort 1: ADX

Experimental group

Description:

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.

Treatment:

Drug: Andecaliximab

Cohort 2: ADX + S-1 + Cisplatin

Experimental group

Description:

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.

Treatment:

Drug: S-1

Drug: Cisplatin

Drug: Andecaliximab

Cohort 3: ADX + S-1 + Oxaliplatin

Experimental group

Description:

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.

Treatment:

Drug: S-1

Drug: Oxaliplatin

Drug: Andecaliximab

Cohort 4: ADX + Nivolumab

Experimental group

Description:

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.

Treatment:

Drug: Nivolumab

Drug: Andecaliximab