Clinical trial NCT02862535: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Gastric Adenocarcinoma
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2016-08-11
Enrollment: 36
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
timeFrame: First dose date up to 82.4 weeks plus 30 days (or if applicable, up to 5 months after permanent withdrawal of nivolumab)
measure: Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
timeFrame: 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:
measure: Cohort 1: Plasma Concentration of Andecaliximab
timeFrame: 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
measure: PK Parameter: Cmax of Andecaliximab
timeFrame: 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)
measure: PK Parameter: AUClast of Andecaliximab
timeFrame: 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)
measure: PK Parameter: AUC0-336h of Andecaliximab
timeFrame: 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)
measure: Number of Participants With Positive Anti-Andecaliximab Antibodies
timeFrame: 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)
Other outcomes:
Locations:
city: Nagoya
country: Japan
city: Osaka
country: Japan
city: Tokyo
country: Japan
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.