Interesting Interview with UBC's Peter Black Dr. Peter Black, TLT's principal investigator for the UBC study site made some interesting comments about the failure of Teqcentric in the SWOG S1605 BCG-unresponsive high risk NMIBC trial. He regards the use of checkpoint inhibitors as monotherapies in this space (including Keytruda) as a dead end.
"...we conducted a futility analysis that did not meet criteria for continuing the trial. However, at the time of this analysis, we had already accrued the intended sample size to the CIS arm of the trial, so we ended up with complete results for these patients.
Three patients died out of 166 who received the drug. Grade 3 or greater adverse events occurred in 13.5% of patients, which was the same as pembrolizumab. These risks have to be matched to the modest efficacy: 20% of patients with CIS were disease-free at 1 year and 14% at 18 months.
Considering the toxicity, death rate, and risk of progression to muscle-invasive bladder cancer, it is challenging to justify the use of immune checkpoint inhibitors in BCG-unresponsive non-muscle invasive bladder cancer. They should be considered a last resort when no other options are available, or if the patient cannot undergo cystectomy. .................
While I cannot speak specifically for atezolizumab, I believe the future of immunotherapy lies in combination therapy rather than single-agent monotherapy. Trials testing combinations like the oncolytic adenovirus CG0070 with pembrolizumab in BCG-unresponsive disease have shown promising results. Nadofaragene firadenovec combined with immunotherapy also seems like a good combination to test, as does N-803—the interleukin-15 super agonist—combined with checkpoint inhibition.