Ms. Kristina Hachey reports
THERALASE(R) PROVIDES UPDATE ON PHASE II BLADDER CANCER CLINICAL STUDY
Theralase Technologies Inc. is providing an update regarding its phase II non-muscle invasive bladder cancer clinical study.
To date, study II has provided the primary study treatment for 63 patients.
In 2016, Kamat et al. stated in the Journal of Clinical Oncology that the International Bladder Cancer Group recommended that: "Single-arm designs may be relevant for the BCG-unresponsive population. Here, a clinically meaningful initial complete response rate (for carcinoma in situ) or recurrence-free rate (for papillary tumours) of at least 50 per cent at six months, 30 per cent at 12 months and 25 per cent at 18 months is recommended."
Based on the 63 patients treated to date, the interim clinical data for study II are presented in the associated table.
Assessment Primary objective Secondary objective Tertiary objective
performance performance performance
# % # % # %
Complete
response 38 64% 17 37% 59 100%
Indeterminate
response 6 10% 2 4% 0 0%
Total response
(CR and IR) 44 75% 19 41% 59 100%
Evaluable
patients 59 46 59
Assessment Patient assessment visit
90 days 180 days 270 days 360 days 450 days
# % # % # % # % # %
Complete response (CR) 33 56% 31 54% 23 43% 20 38% 17 37%
Indeterminate response (IR) 4 7% 10 18% 7 13% 3 6% 2 4%
Total response (CR and IR) 37 63% 41 72% 30 56% 23 44% 19 41%
Evaluable patients 59 57 54 52 46
The study II interim clinical data demonstrate a complete response of 54 per cent at six months, 38 per cent at 12 months and 37 per cent at 15 months, which exceeds the IBCG guidelines.
In addition, the study II interim clinical data demonstrate that at the 90-day assessment visit, 56 per cent of evaluable patients achieved a CR and 63 per cent achieved a total response (CR and IR), while at 450 days, 37 per cent achieved a CR and 41 per cent achieved a TR.
For evaluable patients in study II, who received the optimized study II treatment (after Aug. 1, 2020), the interim clinical data are presented below:
Assessment Patient assessment visit (optimized treatment -- after Aug. 1, 2020)
90 days 180 days 270 days 360 days 450 days
# % # % # % # % # %
Complete response (CR) 29 62% 28 60% 20 45% 17 40% 14 39%
Indeterminate response (IR) 3 6% 9 19% 6 14% 3 7% 2 6%
Total response (CR and IR) 32 68% 37 79% 26 59% 20 48% 16 44%
The interim clinical data for patients who received the optimized study II treatment demonstrate that at the 90-day assessment visit, 62 per cent of evaluable patients achieved a CR and 68 per cent achieved a total response (CR and IR), while at 450 days, 39 per cent achieved a CR and 44 per cent achieved a TR.
The swimmer's plot below is a graphical representation of the interim clinical results (n equals 63) graphically demonstrating a patient's response to a treatment over time. As can be seen in the plot, clinical data are still pending for patients, who have demonstrated an initial CR at 90 days and continue to demonstrate a duration of that response.
The swimmer's plot illustrates:
- 38 evaluable patients achieved CR on at least one assessment date and thus achieved the primary objective of study II (38/59 equals 64 per cent);
- 17 evaluable patients achieved CR at each assessment date (with one patient under review for their 270-and-360-day response) and thus achieved the primary and secondary objectives of study II for all patients assessed up to 450 days (17/46 equals 37 per cent).
The Kaplan-Meier (KM) curve below represents the interim cumulative incidence of clinical events, including the treatment efficacy occurring over a prespecified time in study II.
According to the interim clinical data in the KM curve:
- Greater than 80 per cent of patients remained in study II after 90 days, following the initial study II treatment.
- For all evaluable patients, 41 per cent of total response (TR) have a duration of response greater than 450 days, while 37 per cent of complete response (CR) evaluable patients have a duration of response greater than 450 days.
- For optimized evaluable patients, 44 per cent of TR patients have a duration of response greater than 450 days and 39 per cent of CR have a duration of response greater than 450 days.
For 63 patients treated in study II, there have been 13 serious adverse events (SAEs) reported:
- Two -- Grade 2 (resolved within one and one day, respectively);
- Seven -- Grade 3 (resolved within one, two, three, four, four, 82 and unknown days, respectively);
- Three -- Grade 4 (resolved within three, six and eight days, respectively);
Theralase believes all SAEs reported to date are unrelated to the study II drug or study II device.
In 2020, the Food and Drug Administration granted Theralase fast-track designation (FTD) for study II. As a fast-track designee, Theralase has access to early and frequent communications with the FDA to discuss Theralase's development plans and ensure the timely collection of clinical data to support the approval process. The accelerated communication with the FDA potentially allows the study II treatment to be the first intravesical, patient-specific, light-activated, Ruthenium-based PDC for the treatment of patients diagnosed with BCG-unresponsive non-muscle-invasive bladder cancer carcinoma in situ (with or without recurrent/resected papillary T a/T 1 tumours). FTD can lead to break-through designation (BTD), accelerated approval (AA) and/or priority review, if certain criteria are met.
In mid-2023, the company submitted a pre-BTD submission to the FDA and based on the FDA's feedback, the company is currently working with the clinical study sites (CSSs), a central pathology organization, a biostatistics organization and a regulatory consulting organization to update the pre-BTD with clinical data clarifications identified by the FDA. The company plans to resubmit the pre-BTD submission to the FDA in the first quarter of 2024 for FDA review of these clarifications. Once the pre-BTD submission has been accepted by the FDA, the company plans to compile a BTD submission for review by the FDA in support of the grant of a BTD approval.
Theralase is working to complete enrolment and delivery of the primary study II treatment for all patients in 2024. If successful, this would allow clinical data lock in mid-2026 with a potential Health Canada and FDA approval by 2026/2027.
About study II
Study II utilizes the therapeutic dose of the patented study II drug (0.70 milligram per square centimetre) activated by the proprietary study II device. Study II is focused on enrolling and treating approximately 100 BCG-unresponsive NMIBC carcinoma in-situ patients in up to 15 CSSs located in Canada and the United States.
About Ruvidar
Ruvidar is a patented PDC with 12 years of published peer-reviewed preclinical research and is currently under investigation in study II.
About Theralase Technologies Inc.
Theralase is a clinical stage pharmaceutical company dedicated to the research and development of light activated compounds, their associated drug formulations and the light systems that activate them, with a primary objective of efficacy and a secondary objective of safety in the destruction of various cancers, bacteria and viruses.
We seek Safe Harbor.
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