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

Phase 1
Completed
Conditions
CLDN18.2-positive Gastric Adenocarcinoma
CLDN18.2-positive Adenocarcinoma of the Gastroesophageal Junction
CLDN18.2-positive Adenocarcinoma of Esophagus
Interventions
Registration Number
NCT01671774
Lead Sponsor
Astellas Pharma Global Development, Inc.
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
29
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
IMAB362 + ZAIMAB362Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1.
IMAB362 + ZAZoledronic acidParticipants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1.
IMAB362 + ZA + IL-2 (3 million IU)Interleukin-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.
IMAB362IMAB362Participants received IMAB362 only on Day 1 of each cycle every 3 weeks.
IMAB362 + ZA + IL-2 (3 million IU)IMAB362Participants 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.
IMAB362 + ZA + IL-2 (1 million IU)Interleukin-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.
IMAB362 + ZA + IL-2 (1 million IU)IMAB362Participants 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.
IMAB362 + ZA + IL-2 (1 million IU)Zoledronic acidParticipants 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.
IMAB362 + ZA + IL-2 (3 million IU)Zoledronic acidParticipants 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.
Primary Outcome Measures
NameTimeMethod
Safety and Tolerabilityat 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 kineticsat least 18 months

Descriptive statistics for treatments will be given on the number and activity of immune cells in peripheral blood of patients.

Secondary Outcome Measures
NameTimeMethod
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.

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.

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.

Trial Locations

Locations (9)

Riga East University Hospital, LLC, Latvian Oncology Center

🇱🇻

Riga, Latvia

Leipzig University Hospital, University Cancer Center (UCCL)

🇩🇪

Leipzig, Germany

Institut für Klinische Forschung, Krankenhaus Nordwest GmbH

🇩🇪

Frankfurt, Hessen, Germany

University Hospital Tuebingen, Department of Internal Medicine I - Gastroenterology, Hepatology, Infectious Diseases

🇩🇪

Tübingen, Germany

Piejuras Hospital, Oncology Clinic

🇱🇻

Liepaja, Latvia

Ulm University Hospital, Center for Internal Medicine

🇩🇪

Ulm, Germany

Charité Universitätsmedizin Berlin - CVK, Med. Klinik m.S. Hämatologie und Onkologie

🇩🇪

Berlin, Germany

Freiburg University Medical Center, Department of Internal Medicine II, Gastroenterology and Hepatology

🇩🇪

Freiburg, Germany

BAG / Onkologische Schwerpunktpraxis

🇩🇪

Dresden, Sachsen, Germany

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