Ignite Creation Date:
2024-05-06 @ 3:06 PM
Last Modification Date:
2024-10-26 @ 1:43 PM
Study NCT ID:
NCT04520711
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-08-01
First Post:
2020-08-15
Brief Title:
Hotspot TCR-T A Phase IIb Study of Adoptively Transferred T-cell Receptor Gene-engineered T Cells TCR-T
Sponsor:
Providence Health Services
Organization:
Providence Health Services
Study Overview
Official Title:
Hotspot TCR-T A Phase IIb Study of Adoptively Transferred T-cell Receptor Gene-engineered T Cells TCR-T Targeting Tumor-Specific Neoantigens With in Vivo CD40 Activation and PD-1 Blockade for Patients With Incurable Cancers 2020000584
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a phase IIb study of adoptively transferred T-cell receptor gene-engineered T cells TCR-T targeting tumor-specific antigens with in vivo CD40 activation and PD-1 blockade for patients with incurable cancers The study design is a safety lead-in TCR-T with CD40PD-1 33 followed by Simons Two-Stage expansion design 80 power and 5 one-sided alpha stage-one futility assessment at n 10 stage-two assessment at n 22 accrual up to 24 to allow for potential study drop-out
Detailed Description:
Patients will be infused with T cells engineered to express TCRs targeting one to five tumor-specific antigens expressed by their autologous tumor The number of T cells infused will range from 1e9 to 1e11 Monoclonal antibodies targeting PD-1 pembrolizumab and CD40 CDX-1140 Celldex Therapeutics43 will be administered in that order starting within 24 hours of cell infusion and re-administered at approximately 3 week intervals Clinic visits will include longitudinal evaluation of toxicities and monitoring of immunological parameters The presence or absence of replication competent retrovirus RCR will be evaluated for the first year following adoptive cell transfer or longer if there is evidence of RCR
Tumor Response assessment by RECIST 11 is performed every 9-12 weeks Study treatment continues until progression Option repeat TCR-T infusion is allowed and in addition may incorporate preconditioning chemotherapy using a de-intensified non-myeloablative NMA regimen consisting of a single dose of gemcitabine and a single dose of either cyclophosphamide or epirubicin designed to elicit immunogenic cell death and transient lymphopenia
The primary objective of this study is to determine the safety of the adoptive transfer of TCR-gene engineered T cells targeting TSA in combination with CD40 and PD-1 immunotherapy The secondary objective is to determine whether this therapy can mediate objective clinical responses as determined by objective criteria eg RECIST 11 The study will also characterize the differentiation and functional state of the TCR-gene modified T cells before and after cell therapy and monitor their persistence in the patient after treatment Up to 24 patients will be enrolled in this study Based on published trials treating patients with TCR-transduced T cells adverse events such as fever chills dyspnea hypotension fatigue edema rash and rarely acute cytokine release syndrome may occur
Clinical and immunological data will be analyzed which will determine whether this therapy is safe and effective and whether there are biomarkers or immunological signatures that correlate to efficacy andor lack of efficacy This data will determine whether additional studies are warranted
Tumor Response assessment by RECIST 11 is performed every 9-12 weeks Study treatment continues until progression Option repeat TCR-T infusion is allowed and in addition may incorporate preconditioning chemotherapy using a de-intensified non-myeloablative NMA regimen consisting of a single dose of gemcitabine and a single dose of either cyclophosphamide or epirubicin designed to elicit immunogenic cell death and transient lymphopenia
The primary objective of this study is to determine the safety of the adoptive transfer of TCR-gene engineered T cells targeting TSA in combination with CD40 and PD-1 immunotherapy The secondary objective is to determine whether this therapy can mediate objective clinical responses as determined by objective criteria eg RECIST 11 The study will also characterize the differentiation and functional state of the TCR-gene modified T cells before and after cell therapy and monitor their persistence in the patient after treatment Up to 24 patients will be enrolled in this study Based on published trials treating patients with TCR-transduced T cells adverse events such as fever chills dyspnea hypotension fatigue edema rash and rarely acute cytokine release syndrome may occur
Clinical and immunological data will be analyzed which will determine whether this therapy is safe and effective and whether there are biomarkers or immunological signatures that correlate to efficacy andor lack of efficacy This data will determine whether additional studies are warranted
Study Oversight
Has Oversight DMC:
None
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?:
False
Is an FDA AA801 Violation?:
None