Multicenter, Open-label, Exploratory Phase I Pilot Study to Investigate Safety, Pharmacodynamics, and Pharmacokinetics of Immunological Effects and Activity of Combining Multiple Doses of IMAB362 With Immunomodulation (Zoledronic Acid, Interleukin-2) in Patients With Advanced Adenocarcinoma of the Stomach, the Lower Esophagus, or the Gastroesophageal Junction
Overview
- Phase
- Phase 1
- Intervention
- IMAB362
- Conditions
- CLDN18.2-positive Gastric Adenocarcinoma
- Sponsor
- Astellas Pharma Global Development, Inc.
- Enrollment
- 29
- Locations
- 9
- Primary Endpoint
- Safety and Tolerability
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The purpose of the trial is to assess the immunological effects and their kinetics, the safety and activity of IMAB362 plus Zoledronic acid with/without low to intermediate doses of Interleukin-2 in subjects with advanced gastroesophageal cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed adenocarcinoma of the stomach, the esophagus or the gastroesophageal junction
- •Inoperable locally advanced disease, resections with R0, R1 or R2 outcome or metastatic disease.
- •CLDN18.2 expression confirmed by immunohistochemistry in paraffin embedded tumor tissue sample.
- •Measurable and/or non-measurable disease as defined according to RECIST v1.1
- •Age ≥ 18 years
- •Written informed consent
- •ECOG performance status (PS) 0-1
- •Life expectancy \> 3 months
Exclusion Criteria
- •Prior hypersensitivity reaction or intolerance to one of the compounds of the study treatment
- •Known HIV infection or known symptomatic hepatitis (A, B, C)
- •Clinical symptoms of cerebral metastases
- •Pregnancy or breastfeeding
- •Patients treated with any bisphosphonate-based therapeutic for any indication during the previous year
- •Hypocalcemia that requires medication. Corrected (adjusted for serum albumin) serum calcium \< 8 mg/dl (2 mmol/L) or \> 12 mg/dL (3.0 mmol/L)
Arms & Interventions
IMAB362 + ZA
Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1.
Intervention: IMAB362
IMAB362 + ZA
Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1.
Intervention: Zoledronic acid
IMAB362 + ZA + IL-2 (1 million IU)
Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1 and IL-2 on Days 1 to 3 of Cycles 1 and 3 only.
Intervention: IMAB362
IMAB362 + ZA + IL-2 (1 million IU)
Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1 and IL-2 on Days 1 to 3 of Cycles 1 and 3 only.
Intervention: Zoledronic acid
IMAB362 + ZA + IL-2 (1 million IU)
Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1 and IL-2 on Days 1 to 3 of Cycles 1 and 3 only.
Intervention: Interleukin-2 (1 million IU)
IMAB362 + ZA + IL-2 (3 million IU)
Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1 and IL-2 on Days 1 to 3 of Cycles 1 and 3 only.
Intervention: IMAB362
IMAB362 + ZA + IL-2 (3 million IU)
Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1 and IL-2 on Days 1 to 3 of Cycles 1 and 3 only.
Intervention: Zoledronic acid
IMAB362 + ZA + IL-2 (3 million IU)
Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1 and IL-2 on Days 1 to 3 of Cycles 1 and 3 only.
Intervention: Interleukin-2 (3 million IU)
IMAB362
Participants received IMAB362 only on Day 1 of each cycle every 3 weeks.
Intervention: IMAB362
Outcomes
Primary Outcomes
Safety and Tolerability
Time Frame: at least 18 months
Descriptive statistics for treatments will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped.
Immune cell profile and kinetics
Time Frame: at least 18 months
Descriptive statistics for treatments will be given on the number and activity of immune cells in peripheral blood of patients.
Secondary Outcomes
- Progression-free survival (PFS)(at least 18 months)
- Duration of response (DOR)(at least 18 months)
- Objective tumor response rate (ORR)(at least 18 months)
- Disease control rate (DCR)(at least 18 months)