Thread by @pcvblack

Still digesting #bladdercancer trials at #GU21. QUILT 3.032 trial clinicaltrials.gov/ct2/show/NCT03… testing #N803 in BCG-unresponsive CIS was an important result. Safety data appropriate for intravesical therapy – and CR rate was higher than seen with other drugs in similar trials.
1/n

Note, in case you missed it (as I think most of us did) that the detailed trial results were previously reported as a press release in Dec 2020 yhoo.it/3hfCcWg (unusual for a trial under ASCO embargo?)
2/n

N-803 (aka ALT-803) is a fusion protein: IL15 with N72D mutation (to increase affinity) fused to IL15 receptor (IL15Ra) and IgG1 Fc (improves PK and activity). The resultant IL15 superagonist activates effector NK cells and CD8+ memory T cells, without activation of Tregs.
3/n

N-803 is administered together with BCG according to usual #SWOG schedule for BCG. The rationale for combination was not provided – presumably this immune activation even in the BCG-unresponsive setting is necessary for drug activity.
4/n

The primary endpoint was CR at any time point, which has been used in other similar trials. This was observed in 51 of 72 eligible patients. 71% CR compares to 40-53% in the other trials. KM curve (see #7) suggests that CR occurred at 3 or 6 months in all (or most?) cases.
5/n

However, QUILT allowed for “re-induction” (6 doses?) in patients with persistent disease. Chamie indicated in Q&A that CR rate at 3 months was 55%, which would suggest that 11 patients (15%) were re-induced. Details are lacking here, and more dissection will be needed.
6/n

This is not a flaw, just difference in design. Really important is 12 mo duration of response (presumably from the time point of CR): 56%. May change with longer f/u (only 10.7 mo), but it suggests that more patients are disease free at 12-15 mo than with other drugs (~40%).
7/n

Although the trial enrolled 80 patients, and all 80 were included in calculation of cystectomy-free rate (88% during study period), only 72 were included in the primary endpoint. Further clarification is needed around the fate of the other 8.
8/n

Overall a remarkable trial result. Congratulations to study team including Karim Chamie, @UroCancerMD @WadeJSexton9 @gonzomdphd Look forward to hearing more - as do our patients with BCG-unresponsive CIS!