Ignite Creation Date:
2025-12-24 @ 9:57 PM
Ignite Modification Date:
2026-01-01 @ 12:47 PM
Study NCT ID:
NCT07101432
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-12-08
First Post:
2025-07-28
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Phase I Study of Preconditioning Radiation Therapy With IL-15 Transduced TGFBR2 KO CAR.TROP2-engineered Cord Blood-derived NK Cells in Patients With Advanced Head and Neck Cancer (RADIANCE-NK)
Sponsor:
M.D. Anderson Cancer Center
Organization:
Study Overview
Official Title:
Phase I Study of Preconditioning Radiation Therapy With IL-15 Transduced TGFBR2 KO CAR.TROP2-engineered Cord Blood-derived NK Cells in Patients With Advanced Head and Neck Cancer (RADIANCE-NK)
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To find the recommended dose of an investigational therapy called chimeric antigen receptor (CAR).TROP2/interleukin (IL)15-transduced TGFBR2 KO cord blood (CB)-derived natural killer (NK) cells (TROP2 CAR/IL-15 TGFBR2 KO NK cells) that can be given with and without preconditioning radiation therapy in patients with advanced head and neck squamous cell carcinoma.
Detailed Description:
Primary Objective:
To determine the safety, tolerability, and recommended Phase 2 dose (RP2D) of chimeric antigen receptor (CAR).TROP2/interleukin (IL)15-transduced TGFBR2 KO cord blood (CB)-derived natural killer (NK) cells (TROP2 CAR/IL-15 TGFBR2 KO NK cells) combined with and without preconditioning RT in patients with advanced head and neck squamous cell carcinoma.
Secondary Objectives:
1. To determine the antitumor activity of TROP2 CAR/IL-15 TGFBR2 KO NK cells, including those with pre-CAR-NK bridging SBRT in patients eligible to receive this. Although the clinical benefit of TG TROP2 CAR/IL-15 TGFBR2 KO NK cells has not yet been established (and is currently being investigated in other solid tumors in other clinical trials we have rendered), the intent of offering this treatment is to provide a possible therapeutic benefit and thus, the patient will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability. Efficacy will be determined in each cohort, and for this, we will have a pre-planned subset analysis of patients with metastatic disease where one site is not irradiated.
2. To quantify the persistence of infused allogeneic donor CAR-transduced CB-derived NK cells in the peripheral blood of the recipient.
3. To conduct comprehensive immune modulation studies by evaluating tissue and bloodbased biomarkers associated with response and resistance to TROP2 CAR/IL-15 TGFBR2 KO NK cell infusion.
4. To obtain preliminary data on quality of life and patient experience.
5. To evaluate longitudinal changes in circulating tumor DNA (ctDNA).
Exploratory Objectives:
1. In patients who do not receive SBRT due to ineligibility, they are still eligible to receive CAR-NK cell therapy. This inadvertent biologic randomization may enable cross-sectional comparison of outcomes and correlatives among the patients who receive RT vs. not.
2. To quantify the progression-free survival, overall survival, and the duration of responses of TGFBR2 KO CAR.TROP2/IL15-transduced CB-derived NK cells combined with preconditioning RT in patients with advanced head and neck squamous cell carcinoma.
To determine the safety, tolerability, and recommended Phase 2 dose (RP2D) of chimeric antigen receptor (CAR).TROP2/interleukin (IL)15-transduced TGFBR2 KO cord blood (CB)-derived natural killer (NK) cells (TROP2 CAR/IL-15 TGFBR2 KO NK cells) combined with and without preconditioning RT in patients with advanced head and neck squamous cell carcinoma.
Secondary Objectives:
1. To determine the antitumor activity of TROP2 CAR/IL-15 TGFBR2 KO NK cells, including those with pre-CAR-NK bridging SBRT in patients eligible to receive this. Although the clinical benefit of TG TROP2 CAR/IL-15 TGFBR2 KO NK cells has not yet been established (and is currently being investigated in other solid tumors in other clinical trials we have rendered), the intent of offering this treatment is to provide a possible therapeutic benefit and thus, the patient will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability. Efficacy will be determined in each cohort, and for this, we will have a pre-planned subset analysis of patients with metastatic disease where one site is not irradiated.
2. To quantify the persistence of infused allogeneic donor CAR-transduced CB-derived NK cells in the peripheral blood of the recipient.
3. To conduct comprehensive immune modulation studies by evaluating tissue and bloodbased biomarkers associated with response and resistance to TROP2 CAR/IL-15 TGFBR2 KO NK cell infusion.
4. To obtain preliminary data on quality of life and patient experience.
5. To evaluate longitudinal changes in circulating tumor DNA (ctDNA).
Exploratory Objectives:
1. In patients who do not receive SBRT due to ineligibility, they are still eligible to receive CAR-NK cell therapy. This inadvertent biologic randomization may enable cross-sectional comparison of outcomes and correlatives among the patients who receive RT vs. not.
2. To quantify the progression-free survival, overall survival, and the duration of responses of TGFBR2 KO CAR.TROP2/IL15-transduced CB-derived NK cells combined with preconditioning RT in patients with advanced head and neck squamous cell carcinoma.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2025-05464 | OTHER | NCI-CTRP Clinical Trials Registry | View |