On July 30, 2020 Theralase Technologies Inc. ("Theralase" or the "Company") (TSXV: TLT) (OTCQB: TLTFF), a clinical stage pharmaceutical company focused on the research and development of light activated Photo Dynamic Compounds ("PDC") and their associated drug formulations to safely and effectively destroy various cancers reported to provide an update on its Phase II Non-Muscle Invasive Bladder Cancer ("NMIBC") Clinical Study ("Study II") (Press release, Theralase, JUL 30, 2020, View Source [SID1234568565]).
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The primary purpose of Study II is to discover if the TLD-1433 ("Study Drug") combined with TLC-3200 ("Study Device") (collectively the "Study Treatment") are effective in the destruction of Bacillus Calmette-Guérin ("BCG")-Unresponsive Non-Muscle Invasive Bladder Cancer ("NMIBC").
All Canadian clinical study sites currently remain closed for new patient enrollment and treatment; however, Canadian clinical study sites, who have already enrolled and treated patients, are providing second treatments. The Company is preparing to launch a fifth Canadian clinical study site later in the year.
The Company is preparing to launch a number of US based clinical sites later in the year, subject to the United States economy recovering from COVID-19; however, it is anticipated due to the severity of the COVID-19 pandemic in the United States, that these sites will not be open to commence enrollment and treatment of patients until 2021.
Study II enrolled and treated 12 patients, with the following results:
Patient Status Number of Patients Percentage
First Treatment Provided 12 100.0%
Patients Eligible to Receive Second Treatment 8 66.7%
Second Treatment to be Provided 5 41.7%
Second Treatment Provided 3 25.0%
Response at 90 Days Post Initial Treatment 7 58.3%
Complete Response at 90 Days Post Initial Treatment 3 25.0%
Patients Removed from Study II 4 33.3%
Study II Interim Data Analysis:
Of the 7 patients, who demonstrated a Response to the Study Treatment defined as negative cystoscopy (no evidence of cancer in their bladders) or negative urine cytology (no evidence of the urothelial carcinoma cells in their urine)) at 90 days post initial treatment:
43% achieved a Complete Response ("CR") (negative cystoscopy and negative urine cytology).
43% achieved a Response (negative cystoscopy and positive or suspicious cytology)
14% achieved a Response (suspicious cystoscopy and negative cytology)
The patients who responded to the Study Treatment are currently under medical review to assess the cause of the suspicious cystoscopy by directed bladder biopsy and the cause of the positive or suspicious cytology by repeating the urine cytology analysis. If found to be negative, these patients will be allocated to the CR column. If positive or suspicious again, then Computerized Tomography ("CT") Scan imaging and/or prostatic biopsies will be conducted to rule out Upper Tract Urothelial Cell Carcinoma ("UTUCC"). If UTUCC is proven to exist, then according to FDA’s Bacillus Calmete Guérin ("BCG")-Unresponsive Guidelines to Industry, issued in February 2018, these patients will be classified as CR, as only the bladder was treated by the Study Treatment and not non-addressable areas of the urinary system.
Of the 4 patients that were removed from Study II, the clinical protocol in effect at the time stated in the patient withdrawal criteria that "Patients found to have at Day 90 new T1 high-grade disease, with or without CIS" and "Patients found to have unchanged or worsening CIS at 3 months" will be removed from Study II.
Of the 4 patients removed from the Study, they presented with "unchanged CIS at 3 months".
This was an oversight on behalf of the Company and the clinical protocol has since been updated to remove these two specific patient withdrawal criteria, maintaining the key patient withdrawal criteria of NMIBC progression, which includes "Progression to Muscle Invasive Bladder Cancer ("MIBC")" and "Progression to metastatic disease". These changes, had they been in place, would have led to the retreatment of these 4 patients and an opportunity to achieve CR for these patients at a later medical assessment point.
Study Treatment Optimizations:
Additional optimizations to the clinical study protocol that have been implemented for all future patients to be enrolled and treated in Study II and for the five patients yet to receive their second treatment, include:
Bladder Volume Calculation:
The clinical protocol did not clearly define the bladder volume calculation to be used by the pharmacy and the principal investigator to determine bladder size for administration of the Study Drug and Study Device, respectively. Average bladder volume voided over a 3 day period was used as opposed to a percentage of the maximum bladder volume voided.
Study Device Treatment Time:
The Study Device treatment time was based on detected bladder irradiance, which varied dramatically inside patient bladders due to shape, volume and bladder wall reflection. This led to undertreatment of certain patients with the Study Device by up to 87.9%. This has been modified to now determine Study Device treatment time based solely on the new bladder volumecalculation, resulting in a more consistent Study Device treatment time across patients.
Summary:
The total of these Study II variances (Study Drug Volume, Study Device Volume and Study Device Treatment Time) have led to all 12 patients being undertreated by the Study Treatment from between 30.9% and 154.3%.
About Study II
Study II utilizes the Therapeutic Dose (0.70 mg/cm2) of TLD-1433 and is focused on the enrollment and treatment of approximately 100 BCG-Unresponsive NMIBC patients presenting with Carcinoma In-Situ ("CIS") in approximately 20 clinical study sites located in Canada and the US.
Study II has a:
Primary endpoint of efficacy (defined by CR) at any point in time
Secondary endpoint of duration of CR at 360 days post-initial CR
Tertiary endpoint of safety measured by incidence and severity of Adverse Events ("AEs") grade 4 or higher that do not resolve within 360 days post-initial CR
"For single-arm trials of patients with BCG-unresponsive disease, the FDA defines a CR as at least one of the following:
Negative cystoscopy and negative (including atypical) urine cytology
Positive cystoscopy with biopsy-proven benign or low-grade NMIBC and negative cytology
For intravesical therapies without systemic toxicity, negative cystoscopy with malignant urine cytology, if cancer is found in the upper tract or prostatic urethra and random bladder biopsies are negative.
Intravesical instillation does not deliver the investigational drug to the upper tract or prostatic urethra; therefore, the development of disease in these areas cannot be attributed to a lack of activity of the investigational drug. Thus, sponsors can consider patients with new malignant lesions of the upper tract or prostatic urethra, who have received intravesical therapy to have achieved a CR in the primary analysis; however, sponsors should record these lesions and conduct sensitivity analyses in which these patients are not considered to have achieved a CR." 1