Treatment With Dinutuximab Beta, Zoledronic Acid and Low-dose Interleukin (IL-2) in Patients With Leiomyosarcoma

NCT05080790 | Completed Phase 2 DMC

• 1 other identifier: DiTuSarc / GISG-20
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief Summary

Dinutuximab beta was designed to bind to neuroblastoma cells and other cancer cells that express the GD2 antigen, such as STS/LMS cells, and it is believed that this binding "labels" the cells an makes them a better target. In addition, γδ T cells can safely be expanded in-vivo using intravenous zoledronic acid and subcutaneous interleukin-2 (IL-2) in patients with different types of solid tumors \[Dieli et al., 2007; Pressey et al., 2016\]. It is supposed that combination treatment using dinutuximab beta, zoledronic acid and IL-2 is more effective than their use in isolation. The already-established safety profiles of these agents make testing of the combination in GD2 positive cancers such as GD2 expressing LMS both rational and feasible \[Fisher et al., 2015\].

Conditions

Leiomyosarcoma

Outcome Measures

Primary Outcomes (1)

• The primary objective of this study is to assess the feasibility of the combined treatment with dinutuximab beta, zoledronic acid and low-dose interleukin 2.

  Feasibility rate, defined as the number of patients still on treatment and progression-free at Cycle 4 Day 5 divided by the number of all treated subjects.

  3 years, at EOS

Secondary Outcomes (4)

• A secondary objective of this study is to assess the safety and tolerability of the combined treatment with dinutuximab beta, zoledronic acid and low-dose interleukin 2.

  3 years, at EOS

• An additional secondary objective of this study is to assess the efficacy of the combined treatment with dinutuaseximab beta, zoledronic acid and low-dose interleukin 2.

  3 years, at EOS

• An additional secondary objective of this study is to assess the efficacy of the combined treatment with dinutuaseximab beta, zoledronic acid and low-dose interleukin 2.

  3 years, at EOS

• An additional secondary objective of this study is to assess the efficacy of the combined treatment with dinutuaseximab beta, zoledronic acid and low-dose interleukin 2.

  3 years, at EOS

Other Outcomes (1)

• Tertiary/exploratory objective of this study is to evaluate and compare GD-2 immuno-histochemistry staining on cryopreserved and paraffin-embedded sarcoma tissue samples for future assessment of patient eligibility for anti-GD-2 therapy.

  3 years, at EOS

Study Arms (1)

5 cycles (Q5W) of dinutuximab beta, interleukin-2 and zoledronic acid

EXPERIMENTAL

5 cycles (Q5W) of dinutuximab beta, 20mg/m2/day, interleukin-2, 5.4x10\^6, and zoledronic acid, 4 mg

Drug: Dinutuximab Beta, Zoledronic acid, Interleukin-2

Interventions

Dinutuximab Beta, Zoledronic acid, Interleukin-2 DRUG

Five 5-week cycles (Q5W) of dinutuximab beta, zoledronic acid and low-dose interleukin (IL-2)

5 cycles (Q5W) of dinutuximab beta, interleukin-2 and zoledronic acid

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed leiomyosarcoma.
• ≥ 1 prior systemic therapy for sarcoma, including adjuvant systemic therapy (anthracycline-containing regimen).
• Patients must have a cryopreserved and formalin-fixed paraffin-embedded tumor sample available for submission to central pathology review.
• Signed Written Informed Consent.
• Men and women aged ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Measurable disease.
• Locally advanced/unresectable or metastatic disease.
• No prior therapy with any agent targeting GD2.
• Confirmed GD2-Expression proven on cryopreserved tissue tumor samples. A staining score of 2 on cryopreserved tissue is sufficient for enrollment of the patient.
• No treatment with biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy, or radiation ≤ 21 days before study registration.
• No participation in another clinical trial in the period 30 days prior to start of first dose.
• Patients should have resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE, version 5.0, grade 1 or less.
• Not pregnant and not nursing; for women of childbearing potential who are sexually active, a negative pregnancy test (urinary or serum beta-HCG) done ≤ 7 days prior to treatment start is required.
• Absolute neutrophil count (ANC) ≥ 1,000/mm3.

You may not qualify if:

• Symptomatic, untreated, or uncontrolled brain metastases present.
• Patients with a known history of hypersensitivity to interleukin-2.
• Patients with a hypersensitivity to zoledronic acid or to other bisphosphonates.
• Need for invasive dental procedures. Preventive dental exams should be performed before starting zoledronic acid.
• Patients after allogenic stem cell transplantation or other allogenic organ transplantation (e.g., liver, kidney etc.).
• Patients with different malignant diseases other than sarcoma (measurable manifestations in the last 12 months or active therapy against the other malignant disease in the last 12 months).
• Known active pulmonary disease with hypoxia defined as:
• Oxygen saturation \< 85% on room air or
• Oxygen saturation \< 88% despite supplemental oxygen.
• Uncontrolled intercurrent illness including, but not limited to, poorly controlled hypertension or diabetes, ongoing active infection, or psychiatric illness/social situation that may potentially impair the participant's compliance with study procedures.
• Patients who have received prior anti-GD2 therapy, including chimeric antigen receptor (CAR) T cells directed against GD2 antigen.
• Lactating females are not eligible unless they have agreed not to breastfeed their infants.
• Any condition that, in the opinion of the investigator, would compromise the well-being of the participant or the study or prevent the participant from meeting or performing study requirements.

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead
• RECORDATI GROUP: collaborator

Study Sites (2)

HELIOS Klinikum Bad Saarow

Bad Saarow, 15526, Germany

Location

Helios Klinikum Berlin-Buch

Berlin, 13125, Germany

Location

MeSH Terms

Conditions

Leiomyosarcoma

Interventions

dinutuximab; Zoledronic Acid; Interleukin-2

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2021
• First Posted: October 18, 2021
• Study Start: November 15, 2021
• Primary Completion: January 20, 2025
• Study Completion: January 20, 2025
• Last Updated: August 17, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)