Ignite Creation Date:
2024-05-06 @ 8:28 PM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06390111
Status:
RECRUITING
Last Update Posted:
2024-06-28
First Post:
2024-04-19
Brief Title:
A Trial to Evaluate Efficacy of Reinduction With Nadofaragene Firadenovec in Subjects With CIS High-grade TaT1 and no Complete Response to First Nadofaragene Firadenovec Dose
Sponsor:
Ferring Pharmaceuticals
Organization:
Ferring Pharmaceuticals
Study Overview
Official Title:
A Phase 4 Multi-center Open Label Trial to Evaluate Efficacy of Reinduction With Nadofaragene Firadenovec in Subjects With CIS High-grade TaT1 and no Complete Response to First Nadofaragene Firadenovec Dose
Status:
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:
ABLE-42
Brief Summary:
In this phase 4 trial 000439 subjects with NMIBC CIS high-grade TaT1 who have not responded to their first dose of nadofaragene firadenovec commercial ADSTILADRIN received before trial entry will be offered reinduction when entering the trial
Detailed Description:
Intravesical nadofaragene firadenovec was approved by the US Food and Drug Administration FDA in December 2022 for the treatment of high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumors under the tradename ADSTILADRIN hereafter nadofaragene firadenovec It has only been approved in the US Nadofaragene firadenovec is being developed as a vector-based gene therapy for NMIBC treatment to potentiate durable therapeutic responses by interferon alfa-2b IFN-α2b amplification It is a non-replicating recombinant adenovirus serotype 5 vector containing a transgene encoding the human IFN-α2b gene In addition a single use vial of ADSTILADRIN contains the excipient N-3-cholamidopropyl-N-3-lactobionamidopropyl-cholamide referred to as Syn3NODA that enhances gene transfer across the urothelium
Nadofaragene firadenovec is an efficacious and well tolerated intravesical bladder-sparing therapy which has been investigated in clinical trials from phase 1 to 3 as part of the clinical development program These trials established the safety and clinical efficacy of nadofaragene firadenovec in the treatment of CIS and high-grade TaT1 disease in subjects who are unresponsive to BCG treatment as measured by complete response CR for CIS and high-grade recurrence-free survival for high-grade TaT1
In this phase 4 trial 000439 subjects with NMIBC CIS high-grade TaT1 who have not responded to their first dose of nadofaragene firadenovec commercial ADSTILADRIN received before trial entry will be offered retreatment when entering the trial Retreatment is justified at 3 months after first dose of nadofaragene firadenovec since 3-months follow-up scheme is the standard of care in high-risk NMIBC Retreatment at month 3 is used in a trial investigating intravesical instillation of a IL 15 superagonist nogapendekin alfa inbakicept NAI also known as N 803 and lead to a CR in 46 11 of 24 of the subjects at month 6 Moreover retreatment is a widely accepted concept in immuno-oncology and has been used in IFN α treatment of kidney cancer in the past It is currently also used in an ongoing phase 3 trial investigating the efficacy of oncolytic virus CG0070 in BCG-unresponsive NMIBC In this trial around one third of the subjects who did not respond to the first treatment of CG0070 achieved CR after retreatment at 3 months Therefore it is also expected that a retreatment with nadofaragene firadenovec would show a comparable response rate
In BCG treatment of NMIBC studies show that 40-60 of those who did not respond to initial treatment at 3 months responded at month 6 to a second cycle at month 3 Retreatment has been shown to reduce the frequency of tumor recurrences over standard 6 weeks BCG treatment alone Tumors recurred in 11 of subjects receiving 2 BCG courses vs 29 of subjects treated with initial 6 weeks BCG treatment p003 Further those subjects that received retreatment of BCG had higher CR rates after 6 months and longer disease-free intervals The hypothesis is that first exposure to BCG primes the immune system to enhance anti-tumor effects of subsequent therapy The same principle may apply for nadofaragene firadenovec retreatment The first nadofaragene firadenovec instillation is likely to activate an initial immune response that enhances the antiinflammatory and anti-tumor effects of the second administration As a result subjects with no CR after 3 months may benefit from retreatment with the first dose acting as the stimulator which enhances the anti-tumor effects of the second dose
Nadofaragene firadenovec is an efficacious and well tolerated intravesical bladder-sparing therapy which has been investigated in clinical trials from phase 1 to 3 as part of the clinical development program These trials established the safety and clinical efficacy of nadofaragene firadenovec in the treatment of CIS and high-grade TaT1 disease in subjects who are unresponsive to BCG treatment as measured by complete response CR for CIS and high-grade recurrence-free survival for high-grade TaT1
In this phase 4 trial 000439 subjects with NMIBC CIS high-grade TaT1 who have not responded to their first dose of nadofaragene firadenovec commercial ADSTILADRIN received before trial entry will be offered retreatment when entering the trial Retreatment is justified at 3 months after first dose of nadofaragene firadenovec since 3-months follow-up scheme is the standard of care in high-risk NMIBC Retreatment at month 3 is used in a trial investigating intravesical instillation of a IL 15 superagonist nogapendekin alfa inbakicept NAI also known as N 803 and lead to a CR in 46 11 of 24 of the subjects at month 6 Moreover retreatment is a widely accepted concept in immuno-oncology and has been used in IFN α treatment of kidney cancer in the past It is currently also used in an ongoing phase 3 trial investigating the efficacy of oncolytic virus CG0070 in BCG-unresponsive NMIBC In this trial around one third of the subjects who did not respond to the first treatment of CG0070 achieved CR after retreatment at 3 months Therefore it is also expected that a retreatment with nadofaragene firadenovec would show a comparable response rate
In BCG treatment of NMIBC studies show that 40-60 of those who did not respond to initial treatment at 3 months responded at month 6 to a second cycle at month 3 Retreatment has been shown to reduce the frequency of tumor recurrences over standard 6 weeks BCG treatment alone Tumors recurred in 11 of subjects receiving 2 BCG courses vs 29 of subjects treated with initial 6 weeks BCG treatment p003 Further those subjects that received retreatment of BCG had higher CR rates after 6 months and longer disease-free intervals The hypothesis is that first exposure to BCG primes the immune system to enhance anti-tumor effects of subsequent therapy The same principle may apply for nadofaragene firadenovec retreatment The first nadofaragene firadenovec instillation is likely to activate an initial immune response that enhances the antiinflammatory and anti-tumor effects of the second administration As a result subjects with no CR after 3 months may benefit from retreatment with the first dose acting as the stimulator which enhances the anti-tumor effects of the second dose
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?:
None
Is an FDA AA801 Violation?:
None