RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:What is the Time Line for some Cancer Free NewsDJDawg wrote:
Thanks for all the interesting discussion.
If you consider the first 6 (phase 1), only 3 got the optimized dose. I gather that 2 did well and one was a non responder. It seems in some places on this board people indicate that the non responder was actually a partial responder. Does anyone know. Seems to come up and obviously influences everyone's math as those first 3 are part of the 10 patients ever to recieve an optimized dose from day 1.
A brief review of news excerpts regarding Patients 1 - 6 in Phase 1B:
From May 26, 2017: The Study was designed to treat 3 patients at an initial dose of the PDC (0.35 mg/kg) and included initial monitoring for 30 days, according to the endpoint criteria above.
The DSMB members have unanimously recommended that the first three patients enrolled and treated in the Study successfully achieved the primary and secondary endpoints of the Study and an additional six patients are now eligible to be enrolled into the Study to be treated at a therapeutic dose of the PDC and monitored for 180 days, according to the endpoint criteria.
Dr. Michael Jewett, uro-oncologist at UHN stated that, “I am delighted that a small Canadian company, such as Theralase, has been able to achieve such significant clinical results and in such a short time span. I look forward to Theralase reporting out on the next six patients using the therapeutic dose.”
Roger Dumoulin-White, President and CEO of Theralase stated that, “Theralase thanks the DSMB members for their independent review of the clinical data and their decision that the primary and secondary endpoints for the PDT treatment have successfully been achieved for the first three patients in the Study and their recommendation to continue the Study by enrolling an additional six patients to be treated at the therapeutic dose. Theralase looks forward to successfully reporting out on the performance to the primary and secondary endpoints for the next 6 patients and also the exploratory objective of efficacy of all nine patients, as more clinical data is collected. Theralase has now successfully transformed from a pre-clinical to a clinical oncology organization.”
From July 25, 2017:
These three patients come from a population that has failed standard of care and have remained drug resistant after the standard first line Bacillus Calmette Gurin (“BCG”) course of treatments.
The exploratory efficacy endpoint is being reported at ninety (90) days, in the first 3 patients treated, in the first part of a Phase Ib clinical study (“Study).
The Study is entitled “A Phase Ib Trial of Intravesical Photodynamic Therapy in Patients with Non-Muscle Invasive Bladder Cancer at High Risk of Progression Who are Refractory to Therapy with Bacillus Calmette-Gurin (“BCG”) and Who are Medically Unfit for or Refuse a Cystectomy.
The Study is being used to evaluate TLD-1433 for the: primary endpoint of safety and tolerability, secondary endpoint of pharmacokinetics (movement and exit of drug within tissue) and exploratory endpoint of efficacy.
The Company previously announced on May 26, 2017 that the primary and secondary objectives for the first three patients treated in the Study had successfully been achieved.
The exploratory outcome endpoint in the Study is Recurrence-Free Survival (“RFS”). RFS is defined as the interval from Day 0 (Day of treatment with TLD-1433 Photo Dynamic Therapy (“PDT”)) to documented recurrence or death from any cause, whichever occurs first. Recurrence is defined as any new tumour growth (i.e. any biopsy-confirmed new or recurrent tumour), evaluated at ninety (90) days for the first three (3) patients treated at the MRSD (0.35 mg/cm2) and primarily at ninety (90) days for the next six (6) patients treated at the Therapeutic Dose (0.70 mg/cm2) and secondarily at one hundred and eighty (180) days post treatment.
The first three (3) patients have demonstrated no recurrence of NMIBC lesions at the ninety (90) day cystoscopy analysis. One patient has presented with some reddened areas of the bladder wall, which will be biopsied at a future surgical date. Further clinical analysis will be conducted on the patients according to the approved clinical protocol.
From Nov. 8, 2017:
Interim Data Results:
1) As previously reported, the first three patients treated at the MRSD successfully achieved the primary, secondary and exploratory outcome measures at 90 days post treatment.
2) Patient four treated at the Therapeutic Dose successfully achieved the primary, secondary and exploratory outcome measures at 90 days post treatment. During the 90 day cystoscopy analysis, patient number four’s bladder surface wall was observed to be red and inflamed. The patient will continue to be monitored to see if this condition resolves.
3) Although not a pre-defined outcome measure of the Study, patient one, two and three have successfully achieved the primary and secondary outcome measures at 180 days post treatment.
4) Although not a pre-defined outcome measure of the Study, patient one, two and three have not achieved the exploratory outcome measure at 180 days post treatment.
Discussion:
Patients one and two have a previous history of Upper Urinary Tract Urothelial Carcinoma (“UUTUC”) diagnosed prior to their PDT treatment, while patients 3 and 4 are at high risk of UUTUC. This clinical observation, along with peer-reviewed clinical research1,2 raises the possibility that the source of patient one, two and three’s recurrent NMIBC may have originated by seeding in the bladder from these extravesical sites, potentially confounding the exploratory outcomes for these patients (In this NMIBC patient population, 80% of patients recur, while 50% of patients progress). The extravesical upper tract locations of all treated patients were not exposed to the PDT treatment in the Study.
Although patient one, two and three, treated at the MRSD (1/2 of Therapeutic Dose), recurred at 180 days post treatment; there was no sign of progression of the disease; indicating, that they may benefit from multiple PDT treatments, delivered between 90 to 180 days post treatment.
The interim data obtained to date suggests that the Theralase PDT treatment was able to achieve the primary, secondary and exploratory objectives of the Study at both the MRSD and Therapeutic Dose, delaying recurrence and more importantly delaying progression of NMIBC, for more than 90 days post PDT treatment, which would be of particular benefit for NMIBC patients; especially, patients who do not have a previous history of UUTUC.
From April 16, 2018:
The exploratory outcome endpoint is determined by Recurrence-Free Survival, defined as the interval from Day 0 to documented recurrence or death from any cause, whichever occurs first. Recurrence is defined as any new tumour growth (i.e. any biopsy-confirmed new or recurrent tumour), evaluated at ninety (90) days for the first three patients treated at the Maximum Recommended Starting Dose (“MRSD”) (0.35 mg/cm2) and primarily at ninety (90) days for the last six patients treated at the Therapeutic Dose (0.70 mg/cm2) and secondarily one hundred and eighty (180) days post treatment. Patients who have exceeded the 180 day timeline are no longer monitored as part of the Study.
As previously reported, three patients have successfully been treated at the MRSD (0.35 mg/cm2) showing achievement of the primary, secondary and exploratory endpoints at 90 days post treatment.
The latest three patients, patient four, five and six have been treated at the Therapeutic Dose (0.70 mg/cm2).
The fourth patient developed metastatic urothelial carcinoma, that was detected during a Trans-Urethral Resection of the Bladder Tumour procedure, 138 days after Study treatment. While unusual for NMIBC to metastasize directly to the bone, cases of such progressive disease are known to occur. Given the rapidity of metastases, the treating physicians hypothesize the presence of undetected micro-metastases in the bone were present at the time of Study treatment. Although there was no progressive disease in the bladder, there was evidence of bladder recurrence after treatment. The primary endpoint of safety was nevertheless met in this patient as the therapy was well tolerated with minimal toxicity. The secondary endpoint of pharmacokinetics was also achieved.
The Company, in conjunction with its clinical partner, have optimized the clinical procedure of the Study commencing with patient number five.
As previously reported, the fifth patient was enrolled and treated in January 2018. At the 90 day cystoscopic assessment, completed in April 2018, no tumour recurrence or presence of disease was detected. This patient has now met Study endpoints showing achievement of the primary, secondary and exploratory endpoints at 90 days post treatment.
The sixth patient’s 90-day cystoscopy analysis will be completed in May 2018 to rule out recurrent NMIBC. To date, the patient has shown no clinical evidence or presence of disease.
From May 17, 2018:
As previously reported, the Company, in conjunction with its clinical partner, have optimized the clinical procedure of the Study commencing with patient number five, who was enrolled and treated in January 2018. The treatment was well tolerated by the patient, who demonstrated no tumour recurrence or presence of disease at the 90 day clinical and cystoscopy assessment. This patient has met Study endpoints demonstrating achievement of the primary, secondary and exploratory endpoints at 90 days post treatment.
The sixth patient was treated in February 2018. Patient number six’s 90-day clinical cystoscopy assessment to rule out recurrent NMIBC has now been completed and as reported today, the patient has demonstrated no clinical evidence or presence of disease.
From May 30, 2018: (3 long years ago)
After reviewing the clinical data presented by Girish Kulkarni, MD, PhD, FRCSC, an Associate Professor at the University of Toronto, Department of Surgery and the Principal Investigator of the Study, the MSAB unanimously recommended the early termination of the Study due to achievement of the primary and secondary endpoints. The MSAB also recommended that the clinical data collected from the first three patients treated at the Maximum Recommended Starting Dose (“MRSD”) (0.35 mg/cm2) and the three patients treated at the Therapeutic Dose (0.70 mg/cm2) were sufficient to support the conclusion that the Study had successfully achieved the Study’s primary and secondary endpoints and had adequately addressed the Study’s scientific, technical and clinical questions, as per the approved Study design and clinical protocol. The MSAB recommendation to the Company was to terminate the Study based on the six patients treated to date and suggested that the Company pursue a pivotal Phase II NMIBC clinical study approval with Health Canada and the FDA with efficacy as the primary endpoint.
From May 6, 2019:
Shawn Shirazi, Ph.D., CEO - Drug Division, Theralase stated that, ''Human bladders come in a variety of shapes and sizes and the Company's ACT technology is able to automatically adjust the laser light delivered to the bladder wall in response to these differences through real-time laser light detection. This advanced ACT technology resulted in the Study demonstrating a 66% Complete Response (''CR''), for patients treated at the Therapeutic Dose (0.07 mg/cm2), up to 360 days post treatment. I look forward to the Study sites enrolling and treating patients in a Phase II NMIBC Clinical Study (''Study II'') that has received Health Canada Clinical Trial Authorization and Investigational Testing Authorization, as well as UHN Research Ethics Board approval. Today's conventional therapies for NMIBC patients remains primarily palliative in nature and not curative. It is an honour for an organization, such as AUA to recognize the Company's research and achievements in developing technology to help destroy NMIBC. Theralase is firmly committed to developing the next stand of care for NMIBC''.
September 4, 2019 = First patient treated in Phase II Study.