RE:RE:Anktiva plus BCG Durable CR numbersHi Donein25 - Even though ImmunityBio has marketing approval it looks like they still have to finish their trial. On page 3 of the FDA Approval Letter the
Postmarketing Commitments of ImmunityBio are listed. It doesn't look like the trial will end until 2029.
FDA Approval Letter POSTMARKETING COMMITMENTS SUBJECT TO REPORTING REQUIREMENTS
UNDER SECTION 506B
We remind you of your postmarketing commitment:
4417-1 Complete clinical trial “QUILT-3.032: A Multicenter Clinical Trial of
Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803
(N-803) in Patients With BCG Unresponsive High Grade Non-Muscle
Invasive Bladder Cancer,” and provide annual updates on enrollment,
complete response rate, and duration of response for all patients enrolled
in Cohort 1 (non-muscle invasive bladder cancer [NMIBC] carcinoma in
situ [CIS]). Annual reports should continue until all patients have either
experienced recurrence of high-grade non-muscle invasive bladder
cancer, progression, death, or been lost to follow-up, for up to 4 years.
The timetable you submitted on February 5, 2024, states that you will conduct this study
according to the following schedule:
Interim Report Submission #1: 05/2025
Interim Report Submission #2: 05/2026
Interim Report Submission #3: 05/2027
Interim Report Submission #4: 05/2028
Trial Completion: 05/2029
Final Report Submission: 12/2029
4417-2 Implement a two-tier reference material system with a working reference
material consistent with principles described in ICHQ6B, Specifications:
Test Procedures and Acceptance Criteria for Biotechnological/Biological
Products. Provide the qualification report(s) and requalification protocol for
the working reference materials to the BLA.
The timetable you submitted on April 16, 2024, states that you will conduct this study
according to the following schedule:
Final Report Submission (Qualification Report and Requalification
Protocol): 03/2025
4417-3 Continue to optimize the reduced CE-SDS method to improve precision
and repeatability. Provide a final study report to the BLA which includes
any updates to the analytical procedure and supplemental assay
validation data to support any modifications.
The timetable you submitted on April 16, 2024, states that you will conduct this study
according to the following schedule:
Final Report Submission: 09/2025
4417-4 Continue to optimize the CTLL-2 bioassay method to improve precision.
Include in your studies adjustments to the parallelism criteria, as
appropriate. Provide a final study report to the BLA which includes any
updates to the analytical procedure and supplemental assay validation
data to support any modifications.
The timetable you submitted on April 16, 2024, states that you will conduct this study
according to the following schedule:
Final Report Submission: 06/2025
4417-5 Continue studies to re-validate the ADA and NAb immunogenicity assays
using a more suitable positive control, such as an anti-N-803 affinity
purified antibody. To support the use of this positive control, validation
data should be provided to demonstrate that the positive control can
sufficiently bind to all domains of N-803 (e.g., IL-15 variant, IL-15RαSu
domain, and IgG1 Fc domain) with adequate sensitivity or additional
positive controls (e.g., domain-specific N-803 positive controls) may be
needed to supplement your validation approach. Submit the final assay
validation reports to the BLA. If the validation results in different cut points,
it may be necessary to re-analyze the clinical samples with the new
cut-points. If so, submit the updated ADA and NAb data and analyses in
the next Interim Report for QUILT-3.032.
The timetable you submitted on April 16, 2024, states that you will conduct this study
according to the following schedule:
Final Report Submission: 12/2025
Updated ADA and NAb Data Submission: 05/2025
Submit clinical protocols to your IND 121976 for this product. Submit nonclinical and
chemistry, manufacturing, and controls protocols and all postmarketing final reports to
this BLA. In addition, under 21 CFR 601.70 you should include a status summary of
each commitment in your annual progress report of postmarketing studies to this BLA.
The status summary should include expected summary completion and final report
submission dates, any changes in plans since the last annual report, and, for clinical
studies/trials, number of patients/subjects entered into each study/trial. All submissions,
including supplements, relating to these postmarketing commitments should be
prominently labeled “Postmarketing Commitment Protocol,” “Postmarketing
Commitment Final Report,” or “Postmarketing Commitment Correspondence.”
Donein25 wrote: thanks for the insightful break down Eoganacht. What I also find interesting is that they got approval with just 77 evaluable patients. That is significant because FDA apparently allowed them to just follow the 77 patients 3 years out.
I would think TLT would be given the same type of consideration for possible AA, at or below 100 patients; meaning no new confirmatory trial; follow our CR patients for 3 years.
If you look at the most recent TLT Corporate Presentation it mentions under Study Design: "Patient followed up quarterly for 2 years and then semi-annually for 3 years". That 2 yrs/3 yrs follow up has never been disclosed before (that I can recall) as part of the study design. I have faith that this new study time frame is a directive from FDA that we can obtain AA in the coming year or so and use the follow up 3 years as our confirmatory obligation to full approval.