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

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

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.

Study Overview

• Status: Completed
• Conditions: CLDN18.2-positive Adenocarcinoma of the Gastroesophageal Junction; CLDN18.2-positive Adenocarcinoma of Esophagus; CLDN18.2-positive Gastric Adenocarcinoma
• Intervention / Treatment: Drug: IMAB362; Drug: Zoledronic acid; Drug: Interleukin-2 (1 million IU); Drug: Interleukin-2 (3 million IU)

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Charité Universitätsmedizin Berlin - CVK, Med. Klinik m.S. Hämatologie und Onkologie
  • Freiburg, Germany, 79106
    • Freiburg University Medical Center, Department of Internal Medicine II, Gastroenterology and Hepatology
  • Leipzig, Germany, 04109
    • Leipzig University Hospital, University Cancer Center (UCCL)
  • Tübingen, Germany, 72076
    • University Hospital Tuebingen, Department of Internal Medicine I - Gastroenterology, Hepatology, Infectious Diseases
  • Ulm, Germany, 89070
    • Ulm University Hospital, Center for Internal Medicine
  • Hessen
    • Frankfurt, Hessen, Germany, 60488
      • Institut für Klinische Forschung, Krankenhaus Nordwest GmbH
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • BAG / Onkologische Schwerpunktpraxis
• Latvia
  • Liepaja, Latvia, 3401
    • Piejuras Hospital, Oncology Clinic
  • Riga, Latvia, LV1038
    • Riga East University Hospital, LLC, Latvian Oncology Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2012
• Primary Completion (Actual): October 13, 2014
• Study Completion (Actual): October 13, 2014

Study Registration Dates

• First Submitted: August 21, 2012
• First Submitted That Met QC Criteria: August 21, 2012
• First Posted (Estimate): August 24, 2012

Study Record Updates

• Last Update Posted (Actual): October 18, 2019
• Last Update Submitted That Met QC Criteria: October 16, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antineoplastic Agents; Bone Density Conservation Agents; Zoledronic Acid; Interleukin-2
• Other Study ID Numbers: GM-IMAB-001-04; 2011-005509-64 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."