RE:RE:RE:N-803 median duration of response Hi Enrique...long time no see.
I agree with your NR description. I also believe there is potential to boost the immune response even further with an added treatment(s). For others on the SH board, elderly folk generally have a less robust immune response, which explains why elderly have a propensity to get more acute infections, more complications with acute infections & an increased risk of complications from previous infections (I.e. reactivation of Varicella-Zoster virus = Shingles) that younger people don't get.
It would be interesting to study the potential benefits of adding an extra treatment or two for those who have a PR or NR. As you stated, an NR or PR indicates that CIS is still present. Following the above logic/reality, perhaps getting an extra treatment in this frail age group could better boost the anti-cancer immune response. For certain childhood vaccines, several booster doses are required to achieve optimal protection. I wouldn't be surprised if this is the case for more elderly patients. It could at least provide some explanation for those who lack a durable response or have an early recurrence...or never could convert to CR & remained an NR or PR.
There are plenty of other/future opportunities for this tech, whether it be a variation of the stand-alone approach, a combinational approach, or used as an adjuvant. This ACT/organometallic tech will no doubt be involved in myriad cancer/infectious disease trials over the next decade. All imo....
Your post got me motivated...so starting tomorrow, I will be living a healthier lifestyle (sorry pizza & beer) in order to follow this marathon all the way to the finish line. For those of you with the high BMIs, you are all welcome to join me : ). Good luck...
enriquesuave wrote:
Exactly N-803 plus BCG is a Combination of 2 drugs ( combo trial). The FDA expects a higher efficacy. If we combined TLD-1433 plus Keytruda or with N803 I think we would be 50-100% more effective than N-803 plus BCG. Just IMHO but it's clearly expected to give a synergistic effect. TLD-1433 destroys the Tumors via causing Immungenic Cell Death. An immune response follows, and any drug which can boost the immune response especially if given over several months will obviously result in a much higher efficacy. IMHO.
Just to comment on previous posts about NR patients, I believe NR means CIS still present with or without progression. With progression and patient is out of trial, without progression and patient is given a second Maintenance treatment at day 180, or if NR at day 270, then still followed until end of trial at day 450. CIS still present after a treatment doesn't ean that no effect was achieved, possibly not enough to completely eradicate Tumor. Perhaps made smaller. Any Tumor destruction could lead to an immune response and possibly after a second treatment a more robust response as seen with vaccines after a second dose. Over time some may end up CR perhaps after immune system kicks in? For sure some of these NR patients would become CR in a combination trial. The FDA knows this and will evaluate our results based on the premise that combination therapy will be required for some hard to treat patients. At least we will minimize the number of patients who will require such.
CancerSlayer wrote:
Eoganacht wrote: ImmunityBio has concluded their
Quilt 3.032 trial of N-803 and BCG for BCG-unresponsive NMIBC, presented their final results at
ASCO22 and submitted their BLA to the FDA.
This is from the
ASCO22 presentation by principal investigator Karim Chamie.
"CIS patients have a CR rate of 71% (59/83), with a median duration of CR of 24.1 months in responders" Duration of response means the time from the initial response to progression/death. The definition of median is -
denoting or relating to a value or quantity lying at the midpoint of a frequency distribution of observed values or quantities, such that there is an equal probability of falling above or below it. So it seems that 24 months is the point where half of the responders, or 36%, have progressed or died.
This seems to be a very roundabout way of saying that
the CR rate at 2 years is 36% Given results so far I think the TLD1433 trial has a very good chance of equalling or surpassing these numbers.
Final clinical results of pivotal trial of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive CIS and papillary nonmuscle-invasive bladder cancer (NMIBC) Results:
To date, we enrolled 160 patients (83 CIS, 77 Papillary). In the overall population, median age is 72.3 years, 81% male, with mean number of prior TURBT = 4. Median number of prior BCG doses = 12. CIS patients have a CR rate of 71% (59/83), with a mediation duration of CR of 24.1 months in responders; 91% avoided cystectomy and 96% 24 month bladder cancer specific progression free survival (defined as progression to MIBC). Papillary patients have a 57% 12 month DFS rate, 48% 24 month DFS rate, and 95% avoided cystectomy. Median time to cystectomy in responders (N = 4) is 12.9 months versus 7.8 in non-responders (N = 8) for a 5.1 month delay in cystectomy. PK data shows no systemic levels of N-803; activity is confined to the bladder. Low grade treatment related AEs (grade 1-2) include dysuria (22%), pollakiurua (19%), hematuria (18%), fatigue (16%), and urgency (12%), all other AEs were seen at 7% or less. No treatment related grade 4 or 5 AE were seen. No SAE's were considered treatment related. No immune related SAE's have been seen.
Thanks for that Eoganacht. I appreciate the info. & your optimism...however, I do note that with each of our data updates, I find myself having as many questions as answers ; ).
A CR of 36% at 24+ months is an impressive achievement, but scientifically speaking, it's comparing their sour apples to our sweet oranges. If they were to use N-803 without BCG (without BCG acting like the primary vaccine & N-803 providing the immune boost), I highly doubt they would be able to achieve similar durable response %s. I also believe that using our ACT (with its efficient cell kill & immune boosting capabilities) + BCG, we would more than likely be able to achieve at least similar numbers, & likely higher imo....and perhaps be able to do it with fewer BCG doses? Lots of variant protocols/trials awaiting our ACT. Some Pharmas are likely biting at the bit...