NWBO’s lead candidate - DCVax-L for the most lethal form of brain cancer (GBM) - is currently in Phase III double-blind, randomized, placebo-controlled trial.
The primary endpoint is PFS (progression-free survival), the secondary endpoint is OS (overall survival).
In order to have good chances of being approved, DCVax-L needs to show a 4-month median PFS improvement over the standard-of-care treatment.
SOC median PFS is approx. 6-7 months, SOC median OS is approx. 15-17 months (from the time of screening).
331 patients were enrolled.
A minimum of 233 OS events needed before analyses.
2. Jun 5th clinical trial update
See presentation here:
As of June 5th, 231 OS events happened, the 2 remaining OS events that are needed for the minimum threshold are expected to be reached by mid-July.
Last screening in the trial was 23 months ago. Last enrollment/treatment of patient by DCVax-L was 20 months ago (there’s a 3 month lag between initial screening and enrollment/first dose of DCVax-L).
25% of patients were enrolled between Jun 2008 and Jun 2013,
25% of patients were enrolled between Jun 2013 and Jun 2014,
50% of patients were enrolled between Jun 2014 and Nov 2015.
Approx. 30% of patients are still alive as of today, 23 months after the last patient was screened, suggesting a significant improvement over SOC mOS of 15-17 months.
Given the strong correlation between OS and PFS in GBM clinical trials (see below) there’s a good chance that mPFS would exceed SOC mPFS by 4 months or more.
3. PFS as primary endpoint
OS is the most reliable endpoint in clinical studies and is recommended by FDA. However, PFS has served as primary endpoint for FDA drug approval in the past.
In cancer clinical trials, it’s not uncommon to use PFS as primary endpoint (or so-called “surrogate” endpoint). The company needs to provide FDA with sufficient data to allow a robust evaluation of the correlation between effects on survival (OS) and PFS.
See pages 6-12 here:
Why use PFS? Compared with OS, PFS is an attractive endpoint in clinical trials because it is available earlier, is less influenced by competing causes of death and is uninfluenced by crossover within randomized trials from control to investigational drug and subsequent lines of therapy.
Given that FDA has considered PFS to be an acceptable trial endpoint for accelerated or regular approval, PFS has emerged as the primary endpoint of choice in recent cancer phase III trials.
4. Correlation between PFS and OS
Scientific research suggests that there’s strong correlation between PFS and OS in GBM clinical trials (R squared = 0.7).
Quote from the article:
In glioblastoma, PFS and OS are strongly correlated, indicating that PFS may be an appropriate surrogate for OS. Compared with OS, PFS offers earlier assessment and higher statistical power at the time of analysis.
- Inability to meet primary endpoint (4-month median PFS improvement over standard-of-care treatment);
- No statistical significance in median PFS between control group and treatment group;
- Inability to provide FDA with sufficient data to show strong correlation between PFS and OS.
- New proposed pathway to FDA approval — the "Conditional Approval". Presented to FDA by the Musella Foundation on 6/29/17. See https://virtualtrials.com/fda2017.cfm and https://virtualtrials.com/PDF2017/FDAProposal_v40.pdf
Disclosure: I am/we are long NWBO.