Ignite Creation Date:
2025-12-26 @ 11:48 AM
Ignite Modification Date:
2026-03-01 @ 9:45 AM
Study NCT ID:
NCT02990416
Status:
UNKNOWN
Last Update Posted:
2016-12-13
First Post:
2016-11-28
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A-dmDT390-bisFv(UCHT1) Fusion Protein With Ionizing Radiation and Pembrolizumab for the Treatment of Stage IV Melanoma
Sponsor:
Angimmune LLC
Organization:
Study Overview
Official Title:
Phase I/II Trial of the A-dmDT390-bisFv(UCHT1) Fusion Protein in Combination With Ionizing Radiation and Pembrolizumab for the Treatment of Stage IV Melanoma
Status:
UNKNOWN
Status Verified Date:
2016-12
Last Known Status:
NOT_YET_RECRUITING
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 study evaluates the effectiveness of adding a single four-day treatment of the fusion protein A-dmDT390-bisFv(UCHT1) - plus single palliative tumor radiation - with standard of care KEYTRUDA (Pembrolizumab) therapy for the treatment of metastatic melanoma. The results will be measured by comparing the combined therapy to historical data of KEYTRUDA alone.
Detailed Description:
The purpose of this trial is to test the hypothesis that A-dmDT390-bisFv(UCHT1) can act as an immunomodulator of late stage metastatic melanoma when combined with palliative radiation (to induce the priming of activated T cells with tumor antigens) and Pembrolizumab.
A-dmDT390-bisFv(UCHT1), an anti-T cell immunotoxin is currently being studied as a treatment for cutaneous T cell lymphoma and other CD3+ malignant diseases (NCT00611208 and NCT02943642). During the course of this study, data accumulated that A-dmDT390-bisFv(UCHT1) could be acting as an immunomodulator. This was based on the observation that four out of six partial responses converted to complete responses at times ranging between 6 and 24 months following the completion of the 4-day treatment protocol (serum half life \~45 min.) and no other treatment took place. Complete response durations were 4-6+ years.
Checkpoint inhibitors have revolutionized the treatment of certain solid tumors, notably melanoma, NSCLC and renal cancer. Yet the overall response rate remains low and the mechanisms limiting responses have not been elucidated.
Based on the findings that checkpoint inhibitors have higher response rates when the tumor neoantigen burden is higher (over 1 mutation per megabase, Shumacher \& Schreiber, 2015) the investigators propose to increase the neoantigen burden by combining two distinct manipulations:
1. Treatment with an anti-CD3 fusion protein Resimmune days 1-4 to induce a 20-fold increase in CD8+ central memory T cells and
2. Treatment with anti-PD1 day 16 and q. 3 weeks to block PD-1/PD-L1 negative regulation on the newly activated T cells (Blake et al., 2015) and to block high levels of PD-1 in the tumor microenvironment (Ahmadzadeh et al., 2009).
Palliative tumor radiation day 5 will provide the tumor antigen release needed to convert the expanded central memory T cells to effector memory T cells.
The study will be a single-arm, uncontrolled phase I/II trial to estimate the safely of the combined treatment and then estimate the efficacy in terms of RECIST 1.1 in patients with stage Stage IV metastatic melanoma. The primary endpoint is the clinical response as defined by progression-free survival (PFS). The second end point will be tolerability to treatment. Secondary end points to be considered are overall survival (OS).
The study is conducted in 2 phases. In phase I (safety), the investigators will enroll 6 patients. In first stage, 25 total patients will be enrolled. Using Simon's two stage minimax design for phase II trials, the investigators plan to enroll a maximum of 63 patients.
A-dmDT390-bisFv(UCHT1), an anti-T cell immunotoxin is currently being studied as a treatment for cutaneous T cell lymphoma and other CD3+ malignant diseases (NCT00611208 and NCT02943642). During the course of this study, data accumulated that A-dmDT390-bisFv(UCHT1) could be acting as an immunomodulator. This was based on the observation that four out of six partial responses converted to complete responses at times ranging between 6 and 24 months following the completion of the 4-day treatment protocol (serum half life \~45 min.) and no other treatment took place. Complete response durations were 4-6+ years.
Checkpoint inhibitors have revolutionized the treatment of certain solid tumors, notably melanoma, NSCLC and renal cancer. Yet the overall response rate remains low and the mechanisms limiting responses have not been elucidated.
Based on the findings that checkpoint inhibitors have higher response rates when the tumor neoantigen burden is higher (over 1 mutation per megabase, Shumacher \& Schreiber, 2015) the investigators propose to increase the neoantigen burden by combining two distinct manipulations:
1. Treatment with an anti-CD3 fusion protein Resimmune days 1-4 to induce a 20-fold increase in CD8+ central memory T cells and
2. Treatment with anti-PD1 day 16 and q. 3 weeks to block PD-1/PD-L1 negative regulation on the newly activated T cells (Blake et al., 2015) and to block high levels of PD-1 in the tumor microenvironment (Ahmadzadeh et al., 2009).
Palliative tumor radiation day 5 will provide the tumor antigen release needed to convert the expanded central memory T cells to effector memory T cells.
The study will be a single-arm, uncontrolled phase I/II trial to estimate the safely of the combined treatment and then estimate the efficacy in terms of RECIST 1.1 in patients with stage Stage IV metastatic melanoma. The primary endpoint is the clinical response as defined by progression-free survival (PFS). The second end point will be tolerability to treatment. Secondary end points to be considered are overall survival (OS).
The study is conducted in 2 phases. In phase I (safety), the investigators will enroll 6 patients. In first stage, 25 total patients will be enrolled. Using Simon's two stage minimax design for phase II trials, the investigators plan to enroll a maximum of 63 patients.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: