Safety and Activity of IMAB362 in Combination With Zoledronic Acid and Interleukin-2 in CLDN18.2-positive Gastric Cancer

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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CLDN18.2-positive Gastric Adenocarcinoma, CLDN18.2-positive Adenocarcinoma of the Gastroesophageal Junction, CLDN18.2-positive Adenocarcinoma of Esophagus

Intervention / Treatment
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* Drug: IMAB362
* Drug: Zoledronic acid
* Drug: Interleukin-2 (1 million IU)
* Drug: Interleukin-2 (3 million IU)


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMAB362 + ZA<br>Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1. | Drug: IMAB362<br>* 800 mg/m2 on d 1 of cycle 1. 600 mg/m2 on d 1 of every other cycle<br>Drug: Zoledronic acid<br>* 4 mg on d 1 of cycle 1 and cycle 3<br>|
| Experimental: IMAB362 + ZA + IL-2 (1 million IU)<br>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. | Drug: IMAB362<br>* 800 mg/m2 on d 1 of cycle 1. 600 mg/m2 on d 1 of every other cycle<br>Drug: Zoledronic acid<br>* 4 mg on d 1 of cycle 1 and cycle 3<br>Drug: Interleukin-2 (1 million IU)<br>* 1 million IU on day 1, 2 and 3 of cycles 1 and 3.<br>|
| Experimental: IMAB362 + ZA + IL-2 (3 million IU)<br>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. | Drug: IMAB362<br>* 800 mg/m2 on d 1 of cycle 1. 600 mg/m2 on d 1 of every other cycle<br>Drug: Zoledronic acid<br>* 4 mg on d 1 of cycle 1 and cycle 3<br>Drug: Interleukin-2 (3 million IU)<br>* 3 million IU on day 1, 2 and 3 of cycles 1 and 3.<br>|
| Active Comparator: IMAB362<br>Participants received IMAB362 only on Day 1 of each cycle every 3 weeks. | Drug: IMAB362<br>* 800 mg/m2 on d 1 of cycle 1. 600 mg/m2 on d 1 of every other cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | Descriptive statistics for treatments will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped. | at least 18 months | 
| Immune cell profile and kinetics | Descriptive statistics for treatments will be given on the number and activity of immune cells in peripheral blood of patients. | at least 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | 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. | at least 18 months | 
| Objective tumor response rate (ORR) | 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. | at least 18 months | 
| Disease control rate (DCR) | 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. | at least 18 months | 
| Duration of response (DOR) | 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. | at least 18 months |