Theralase Technologies Inc. V.TLT

RE:RE:URO TODAY Article

[gojotv!]

These results speak well for our TLD-1433, since the most effective competitor is treating and re-re-re-treating, while our trial gives high results after only two treatments...
Factor in our low toxicity, and applicability to other cancer types and even viruses... and what we have here is a winner!
Good luck to all patients and to patient investors!

ScienceFirst wrote: 2 competitors.  Below, I will document the pros and cons.

August 2022 - An Update on Key Areas of Progress In Bladder Cancer

BCG-unresponsive bladder cancer

For patients with high-grade NMIBC (intermediate high-risk papillary tumors or CIS), intravesical BCG after TURBT is an established and effective therapy to help prevent recurrence and reduce the likelihood of progression. Nonetheless, recurrence or progression do occur, creating a pressing need for alternative treatments. Such therapies also could benefit patients who cannot access BCG due to the ongoing global shortage.

Several recent and ongoing studies in BCG-unresponsive disease are particularly noteworthy. At ASCO 2022, we saw encouraging data from an interim analysis of the phase 2, single-arm CORE-001 study, in which patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS) received the investigational oncolytic vaccine CG0070 in addition to intravenous Keytruda (pembrolizumab). Among 16 evaluable patients, 14 (87.5%) showed a complete response (CR) to treatment at 3-month assessment, all of whom remained in CR for up to 12 months of follow-up.14 This is a striking improvement on the prior benchmark of 20% to 25% for CR to therapies for BCG-unresponsive NMIBC with CIS. CG0070, an adenovirus serotype 5 engineered to express granulocyte-macrophage colony stimulating factor (GM-CSF), selectively replicates within tumor cells that have mutated or deficient retinoblastoma (RB) gene, which leads to cell lysis and immunogenic cell death. Early safety data in CORE-001 were promising: no grade 3, 4, or serious adverse events (AEs) were attributed to treatment. The study continues to recruit patients, with final results expected in 2023.

Also at ASCO 2022, we also saw intriguing data from the multicenter, open-label, phase 3 QUILT-3.032 trial, in which patients with BCG-unresponsive high-grade NMIBC with CIS or papillary disease received intravesical therapy with BCG and N-803, an investigational high-affinity interleukin (IL)-15 immunostimulatory fusion protein.15 N-803 promotes the proliferation and activation of natural killer (NK) cells and CD8+ T cells, but not regulatory T cells, which are thought to suppress the immune system’s antitumor response.16,17 In the QUILT-3.032 study, primary endpoints were met for patients with both CIS (CR rate, 71% [59/83 patients]; median duration of response, 24.1 months) and papillary disease (53% of patients were disease-free at 18 months). Among 160 evaluable patients, more than 90% had avoided cystectomy after 2 years of follow-up. Four (3%) patients had grade 3 or worse treatment-related AEs, but no serious AEs were classified as treatment-related or immune-related—the most common AEs were dysuria, pollakiuria, and hematuria, each of which affected approximately 20% of treated patients. This rate is remarkably low, especially in light of the fact that single-agent BCG typically leads to AEs in more than 50% of patients.

Results from both CORE-001 and QUILT-3.032 are very promising. Although CG0070 and N-803 are investigational and not ready for prime time, their performance in these studies shows how we are raising the bar for our patients with BCG-unresponsive NMIBC. While cross-study comparisons are fraught with pitfalls, discussions with patients often center around the fact that pembrolizumab monotherapy produced a 12-month CR rate of just under 18% when evaluating all patients with BCG-unresponsive NMIBC who received at least one treatment dose in the registrational KEYNOTE-057 trial.18



N-803 + BCG:

It's still dependent on BCG.  BCG is still on shortage and will remain so, for many years.

This drug is instilled for 2 hours twice weekly for 6 weeks, then weekly for 6 weeks. The maintenance regimen is instillation every 2 weeks for up to 2 years.



CG0070 + Keytruda:

Keytruda being involved in this combo, it would fit only about 25% of the eligible candidates.  And for eligible candidates, the treatment involves many doses.  See below.

 

 

June 26, 2022:

 

Roger Li, MD, Reviews Efficacy of CG0070 Plus Pembrolizumab for BCG-Unresponsive NMIBC

 

Roger Li, MD, a genitourinary oncologist from the Moffitt Cancer Center, spoke with CancerNetwork® at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting about the results of the phase 2 CORE1 trial (NCT04452591) which looked at CG0070, an oncolytic vaccine, plus pembrolizumab (Keytruda) for patients with non–muscle invasive bladder cancer who were unresponsive to bacillus Calmette-Guerin (BCG).1 The primary end point of the trial was the complete response (CR) rate which was 92% overall. Drilling down by timepoint, the CR rate at 6 months was 88%, at 9 months it was 82%, and at 12 months it was 75%.

 

Transcript:

 

The CR rate, which is our primary end point for the CORE1 trial, is set at the 12-month mark. Because these patients have a non–muscle invasive recurrence, the gold standard treatment is radical cystectomy which is the removal of the bladder. It’s a very morbid procedure and is completely life-altering for many patients. In addition, there are many patients who are elderly and frail and cannot undergo the procedure. It’s important for us to use salvage therapy to help patients preserve their bladders. Because of that, we’re looking at long-term CR rates so that we not only get a CR up front, but we help patients preserve their bladders for the long term. We use the 12-month mark and CR rate as the primary end point. Six out of 8 patients who have reached that time point continue to have a CR.

 

In the past in the [phase 2] KEYNOTE-057 trial [NCT02625961], which used pembrolizumab as the treatment agent for a similar cohort of patients, the 3-month CR rate was 41%.2 In comparison, ours is over 90%. So, 22 of 24 patients did derive a CR at the 3-month mark from our trial. [This is] encouraging both in the early time point CR rate, as well as at the 12-month mark.

Treatment:

 

Experimental: Single Arm

Patients with carcinoma in situ with or without concomitant high-grade Ta or T1 papillary disease.

CG0070 will be administered intravesically (IVE) following a sequence of bladder washes with 5% DDM and normal saline. CG0070 will be administered weekly x 6 on Weeks 1, 2, 3, 4, 5, and 6. If the patient has persistent high-grade disease at Week 13, the patient will receive another cycle of 6 weekly treatments. If there is no disease present at Week 13 (e.g. complete response) then the patient will receive 3 weekly treatments.

Beginning at Week 25, patients will receive weekly x 3 treatments every 12 weeks through week 49 then every 24 weeks thereafter.