For the primary objective, 65% of Evaluable Patients (Patients evaluated by a Principal Investigator ("PI")) achieved a Complete Response ("CR") at any assessment date post primary Study Treatment and 30% of Evaluable Patients achieved a CR at 450 days.
TORONTO, ON / ACCESSWIRE / May 10, 2023 / 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 (" PDCs") and their associated drug formulations, used to safely and effectively destroy various cancers, bacteria and viruses, announced today an update on its recently reported Phase II clinical study ("Study II") interim clinical data.
Background:
Study II was designed to treat patients diagnosed with Bacillus Calmette-Gurin ("BCG")-Unresponsive, Non-Muscle Invasive Bladder Cancer ("NMIBC") Carcinoma In-Situ ("CIS") (with or without resected papillary Ta/T1 disease) with a patented investigational study drug Ruvidar™ (TLD-1433 - a ruthenium based PDC intravesically instilled into a patient's bladder), subsequently activated by a proprietary investigational study device (TLC-3200 Medical Laser System - a green (520 nm) laser system equipped with fiber-optic light emitters and detectors).
In recent discussions with the Medical and Scientific Advisory Board ("MSAB") for Study II, the MSAB advised the Company to review the FDA Guidance to Industry1 on how to best classify Indeterminate Response ("IR") patients (patients assessed with negative cystoscopy and positive urine cytology), where the source of the positive urine cytology has not been determined.
The FDA Guidance to Industry1 states as follow:
"For single-arm trials of patients with BCG-unresponsive disease, the FDA defines a complete response 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, the FDA includes, in the definition of a complete response, 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 complete response 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 complete response.
Systemic therapies are expected to have a treatment effect throughout the urinary tract. Therefore, a patient who received systemic therapy cannot be considered to have a complete response if the patient has a malignant lesion(s) in the upper tract or prostatic urethra.
For the purposes of determining the duration of a complete response, the FDA defines a recurrence as findings on follow-up that no longer meet the above definition for a complete response.
The protocol should provide a plan for the evaluation of patients with suspicious urine cytology. Suspicious cytology does not include the presence of atypical cells. This plan should specify how a suspicious urine cytology will affect the initial definition of complete response and the duration of complete response. For example, the plan may include repeat cytologies or random bladder biopsies.
Regardless of the prespecified plan, all investigators should evaluate suspicious urine cytology in the same manner. The goal of therapy in patients with BCG-unresponsive NMIBC is to avoid cystectomy."
Theralase®'s Study II treats patients with an intravesical study drug activated by an intravesical study device. In accordance with the FDA Guidance to Industry1, patients enrolled and provided the primary study treatment, where the source of the positive urine cytology has not been identified (i.e.: upper tract or prostatic urethra Urothelial Cell Carcinoma ("UCC")) and confirmatory bladder biopsies were negative, Theralase® has reclassified these patients from Indeterminate Response ("IR") to Complete Response ("CR").
For patients, who have been enrolled and provided the primary study treatment in Study II, that have been diagnosed as IR and do not have confirmatory negative bladder biopsies (confirming that the source of the UCC is not from the bladder wall), then these patients have remained classified as IR, until additional clinical assessments can be completed by the PIs to prove or disprove a diagnosis of CR.
As a result, Theralase® is providing an update to Study II's interim clinical study data analysis, where some patients have been reclassified from IR to CR on certain assessment days.
In accordance with the FDA Guidance to Industry1, Theralase® will conduct sensitivity analyses, in which these IR patients are considered not to have achieved a CR, as a part of the final clinical report.