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

NCT01671774 | Completed Phase 1 DMC

• 2 other identifiers: GM-IMAB-001-042011-005509-64
• Study Type: interventional
• Target: 29
• Locations: 2 countries
• Sites: 9

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Progression-free survival (PFS)

  at least 18 months

• Objective tumor response rate (ORR)

  at least 18 months

• Disease control rate (DCR)

  at least 18 months

• Duration of response (DOR)

  at least 18 months

Study Arms (4)

IMAB362 + ZA

EXPERIMENTAL

Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1.

Drug: IMAB362; Drug: Zoledronic acid

IMAB362 + ZA + IL-2 (1 million IU)

EXPERIMENTAL

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; Drug: Zoledronic acid; Drug: Interleukin-2 (1 million IU)

IMAB362 + ZA + IL-2 (3 million IU)

EXPERIMENTAL

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; Drug: Zoledronic acid; Drug: Interleukin-2 (3 million IU)

IMAB362

ACTIVE COMPARATOR

Participants received IMAB362 only on Day 1 of each cycle every 3 weeks.

Drug: IMAB362

Interventions

IMAB362 DRUG

800 mg/m2 on d 1 of cycle 1. 600 mg/m2 on d 1 of every other cycle

IMAB362; IMAB362 + ZA; IMAB362 + ZA + IL-2 (1 million IU); IMAB362 + ZA + IL-2 (3 million IU)

Zoledronic acid DRUG

4 mg on d 1 of cycle 1 and cycle 3

IMAB362 + ZA; IMAB362 + ZA + IL-2 (1 million IU); IMAB362 + ZA + IL-2 (3 million IU)

Interleukin-2 (1 million IU) DRUG

1 million IU on day 1, 2 and 3 of cycles 1 and 3.

IMAB362 + ZA + IL-2 (1 million IU)

Interleukin-2 (3 million IU) DRUG

3 million IU on day 1, 2 and 3 of cycles 1 and 3.

IMAB362 + ZA + IL-2 (3 million IU)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (9)

Institut für Klinische Forschung, Krankenhaus Nordwest GmbH

Frankfurt am Main, Hesse, 60488, Germany

Location

BAG / Onkologische Schwerpunktpraxis

Dresden, Saxony, 01307, Germany

Location

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

Berlin, 13353, Germany

Location

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

Freiburg im Breisgau, 79106, Germany

Location

Leipzig University Hospital, University Cancer Center (UCCL)

Leipzig, 04109, Germany

Location

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

Tübingen, 72076, Germany

Location

Ulm University Hospital, Center for Internal Medicine

Ulm, 89070, Germany

Location

Piejuras Hospital, Oncology Clinic

Liepāja, 3401, Latvia

Location

Riga East University Hospital, LLC, Latvian Oncology Center

Riga, LV1038, Latvia

Location

Related Publications (1)

• Lordick F, Thuss-Patience P, Bitzer M, Maurus D, Sahin U, Tureci O. Immunological effects and activity of multiple doses of zolbetuximab in combination with zoledronic acid and interleukin-2 in a phase 1 study in patients with advanced gastric and gastroesophageal junction cancer. J Cancer Res Clin Oncol. 2023 Aug;149(9):5937-5950. doi: 10.1007/s00432-022-04459-3. Epub 2023 Jan 6.

  PMID: 36607429 DERIVED

Related Links

• Link to plain language summary of the study on the Trial Results Summaries website

MeSH Terms

Interventions

zolbetuximab; Zoledronic Acid; Interleukin-2

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2012
• First Posted: August 24, 2012
• Study Start: October 16, 2012
• Primary Completion: October 13, 2014
• Study Completion: October 13, 2014
• Last Updated: November 14, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (7); LA (2)