CLDN18.2-positive Adenocarcinoma of Esophagus, CLDN18.2-positive Adenocarcinoma of the Gastroesophageal Junction, CLDN18.2-positive Gastric Adenocarcinoma
Conditions
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.
Interventions
DRUGInterleukin-2 (3 million IU)
3 million IU on day 1, 2 and 3 of cycles 1 and 3.
DRUGIMAB362
800 mg/m2 on d 1 of cycle 1. 600 mg/m2 on d 1 of every other cycle
DRUGZoledronic acid
4 mg on d 1 of cycle 1 and cycle 3
DRUGInterleukin-2 (1 million IU)
1 million IU on day 1, 2 and 3 of cycles 1 and 3.
Sponsors
Astellas Pharma Global Development, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | at least 18 months | PFS is defined as the time from registration of therapy to the first observation of disease progression or death from any cause or last tumor evaluation if free of progression. For patients who have not progressed either clinically or on the last scan, they will be censured as of the last tumor evaluation. |
| Objective tumor response rate (ORR) | at least 18 months | ORR comprises the fraction of patients with CR, PR according to RECIST v1.1. It is set in relation to the ITT population and PP population. |
| Disease control rate (DCR) | at least 18 months | DCR is defined as the fraction of patients with CR or PR or SD according to RECIST v1.1. It is set in relation to the ITT population and PP population. |
| Duration of response (DOR) | at least 18 months | Duration of response is determined as the time when criteria for CR, PR, and SD are first met until the first date that recurrent or progressive disease or death occurs. |
Countries
Germany, Latvia
Outcome results
None listed