Gene Therapy for NMIBC

Dtat60,

After some further thinking, the idea of installing an interferon factory in the bladder is quite similar to (one school of thought) about the lasting effect of BCG for those who respond to BCG - that BCG becomes resident and detectable in bladder tissue for a long (years) period of time, and is active against recurrence.

This leads to a question, for which I am looking for information. What results are achieved in patients that have been previously been treated with intrarvesical Interferon and/or combination treatment with BCG + Interferon ?  Both being common treatment options during BCG shortages an following BCG failure.

Anyone come across such data ?

Thanks
Jack

There is limited info, including some study results,  on Clinicaltrials.gov.

clinicaltrials.gov/ct2/results?cond=Bladder+Cancer&term=Nadofaragene+firadenovec&cntry=&state=&city=&dist=

Best,
Jack

This is interesting. Thanks for posting. The article sounds very positive but I guess I'm not sure how to interpret the 12 month response rates. Is the overall complete response rate of 30.5% and 24.3% for CIS considered successful in clinical trails? I'm not familiar with how the clinical trails are judged but it seems like a large drop off from the 3 month rates ( 59.6% and 53.4) to the 12 month rates. 

I"m also trying to find out more information on Photodynamic Therapy for BCG failure NMIBC. Here is on article from 2018.

news.cancerconnect.com/bladder-cancer/photodynamic-therapy-a-promising-treatment-for-superficial-bladder-cancer-ES5Va1EhcE6qmuwEfMu8fw   

This is really interesting. I did a little more investigating and found a report on this clinical trial that was easier for me to understand, here:
www.medscape.com/viewarticle/935277

It sounds like there will be a favorable option in the future for persons who don't have a favorable outcome from BCG treatments. This is really great news.

Nadofaragene firadenovec, a novel intravesical therapy for nonmuscle-invasive bladder cancer (NMIBC) that does not respond to bacillus Calmette- Guérin (BCG) therapy shows efficacy across important patient subgroups, investigators reported at SUO 2020, the virtual annual meeting of the Society of Urologic Oncology.

In the original phase 3 trial of 157 patients with high-grade BCG-unresponsive NMIBC, clinicians delivered nadofaragene firadenovec (also known as rAd-IFNa/Syn3), a non-replicating adenovirus vector-based gene therapy containing the gene interferon alfa-2b, by catheter into the bladder epithelium once every 3 months. The 3-month complete response rate was 59.6% overall and 53.4% in patients with carcinoma in situ (CIS) with or without Ta or T1 tumors. In addition, 72.9% of patients with high-grade Ta or T1 tumors and no CIS had freedom from high-grade recurrence. At 12 months, 30.5% overall, 24.3% of patients with CIS (with or without Ta or T1 tumors), and 43.8% of patients with high-grade Ta or T1 tumors (and no CIS) were free from high-grade recurrence.

For both the CIS and high-grade Ta/T1 only cohorts, there were no significant differences in response rates at 3 and 15 months between male and female patients, patients younger and older than 70 years, BCG-refractory vs BCG-relapsed disease, patients with more or less than 3 prior lines of therapy, number of prior non-BCG regimens, and patients with more or less than 3 prior courses of BCG, Vikram Narayan, MD, of Emory University in Atlanta, Georgia, reported.

Duration of response also did not differ significantly among groups, Dr Narayan reported. Only in the CIS cohort, patients who received 3 or fewer prior courses of BCG had significantly longer duration of response compared with patients who received more than 3 courses: 12.68 vs 4.96 months. A multivariable analysis confirmed that none of these baseline characteristics or prior therapy significantly influenced response rates at 3 and 15 months or duration of response.

www.renalandurologynews.com/home/conference-highlights/annual-meeting-of-the-society-of-urologic-oncology/suo-2020/intravesical-gene-therapy-efficacy-nonmuscle-invasive-bladder-cancer-patients-features/