A First-In-Human Phase 1 Trial of T-Cell Membrane-Anchored Tumor Targeted Il12 (Attil12)- T-Cell Therapy in Subjects With Advanced/Metastatic Soft Tissue and Bone Sarcoma

Phase 1

Active, not recruiting

• Conditions: Soft Tissue Sarcoma; Bone Sarcoma
• Interventions: Drug: Cyclophosphamide; Drug: attIL2-T cells

• Registration Number: NCT05621668
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

To find a recommended dose of attIL2-T cell therapy that can be given to patients with soft tissue or bone sarcomas and to see if it can help to control the disease.

Detailed Description

Primary Objective:

1. Part A. Determine the safety, maximum tolerated dose and/or recommended phase 2 dose of adoptively transferred T cell membrane-anchored tumor targeted IL12 (attIL12)-T cells in combination with cyclophosphamide in patients with advanced/metastatic soft tissue or bone sarcomas

2. Part B. Characterize the safety and tolerability and assess preliminary efficacy of attIL12-armed T cells in combination with cyclophosphamide by evaluating the 4-month disease control rate (DCR4 months) in patients with recurrent unresectable osteosarcoma

Secondary Objectives:

1. Evaluate the anti-tumor efficacy achieved following adoptive transfer of T cellmembrane-anchored tumor targeted IL12 (attIL12)-T cells in combination with cyclophosphamide in patients with advanced/metastatic soft tissue or bone sarcomas

Exploratory Objectives:

1. Characterize the immune response following adoptive transfer of T cell membrane-anchored tumor targeted IL12 (attIL12)-T cells in paired in pre-treatment and on-treatment tumor specimens and peripheral blood samples

2. Assess FoxP3/CD33/CD8/IFNg expression in pre-treatment and on-treatment tumor specimens and correlate with clinical benefit/anti-tumor response

3. Determine changes in cell surface vimentin (CSV)-positive circulating tumor cells (CTCs) in peripheral blood before and after adoptive transfer of T cell membrane-anchored tumor targeted IL12 (attIL12)-T cells and correlate with clinical benefit/anti-tumor response

Study Timeline

• Study First Submitted: 2022-11-10
• Study First Submitted QC: 2022-11-10
• Study First Posted: 2022-11-18
• Study Start: 2023-09-08
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-26
• Last Update Posted: 2025-04-01
• Primary Completion: 2025-09-30
• Study Completion: 2025-09-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Part A: Dose Findings (MTD)	attIL2-T cells	The dose of attIL2-T cell therapy the participants will receive will depend on when the participants joined this study. The first group of participants will receive the lowest dose level of attIL2-T cell therapy.
Part B: Osteosarcoma Dose Expansion	attIL2-T cells	Participants will receive attIL2-T cell therapy at the recommended dose that was found in Phase 1.
Part A: Dose Findings (MTD)	Cyclophosphamide	The dose of attIL2-T cell therapy the participants will receive will depend on when the participants joined this study. The first group of participants will receive the lowest dose level of attIL2-T cell therapy.
Part B: Osteosarcoma Dose Expansion	Cyclophosphamide	Participants will receive attIL2-T cell therapy at the recommended dose that was found in Phase 1.

Primary Outcome Measures

Name	Time	Method
To examine the incidence of adverse events.	through study completion; an average of 1 year.	National Cancer Institute, Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. from screening through the treatment period

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States