NorthWest Biotherapeutics Inc (NWBO)

[sentiment_stocks]

So this article entitled "Dendritic cell vaccination for glioblastoma multiforme patients: has a new milestone been reached?" from 7-28-23 is a decently positive one.
https://cdn.amegroups.cn/journals/pbpc/files/journals/3/articles/77315/public/77315-PB1-6789-R1.pdf

Journal: Translational Cancer Research
Authors: Stefaan W. Van Gool^, Jennifer Makalowski, Linde F. C. Kampers, Peter Van de Vliet, Tobias Sprenger, Volker Schirrmacher, Wilfried Stücker

Some sections that stood out to me:

In the current phase III report of the data obtained along the phase IIb randomization, the OS, originally a secondary read- out, became the primary endpoint as PFS was deemed too challenging to monitor reliably. An external control arm (ECA) was designed on the basis of reported control groups in contemporary and closely matched RCTs in literature, both for patients with newly diagnosed as for relapsed GBM. Because of lack of individual patient data, a matching- adjusted-indirect-comparison (MAIC) analysis was used. Regulatory techniques were used to change the read-out and trial design, aiming to preserve the good clinical practice label of the trial. So, we end up with a phase III prospective non- randomized externally controlled cohort trial of randomized patients in a phase IIb cross-over study design. The fact that the patients were recruited and “prospectively” analyzed for OS, and an ECA was created, still allowed the term “trial”.

Only by designing a completely new trial, the OS could gain enough weight as phase III-level information to assess the treatment outcome. (ii) The matching with the ECA can be considered as a weakness, but was performed by an independent third- party organization using pre-specified matching criteria and state of the art methodologies. (iii) Finally, the inclusion and randomization were placed about 3 months after surgery. This is a time window in which already about one fifth to one fourth of patients might become progressive again. The study explicitly mentions that patients having radiographic evidence of early disease progression following radiochemotherapy were excluded for randomization. Those type of patients, however, were included in the studies that delivered the ECA. Therefore, we have to conclude that patients with worse prognosis were present in the OS data of the ECA, but were not present in the OS data of this study. Nevertheless, the authors specifically conducted a sensitivity analysis precisely to address this critical point (1). In the sixth sensitivity analysis, published in the supplements, two of the five comparator studies were dropped because it was not clear whether they had excluded patients with early progression, and the HR remained the same (0.8). This demonstrates that the authors recognized the potential of early progression to influence the OS, and addressed it appropriately. The results showed that at least in this study there was no effect from this potentially confounding factor, making the improvement of OS due to DCVax®-L reliable. Moreover, the significant OS data and strong hazard ratio observed in the relapsed patients and their matched ECA might have the strongest value and might be most meaningful to demonstrate efficacy of DCVax®-L.

Can the scientific community consider this publication (1) as a new milestone in the development of DC vaccination as active specific immunotherapy, aimed to improve the OS of patients with GBM? The answer is definitively yes. It is the first phase III controlled report that shows an improvement of the OS in patients with GBM. For the first time, a level I of clinical research evidence in evidence-based medicine is reached, and extends the level IIa clinical research evidence already observed with systematic reviews of phase I or II clinical trials (8-13).

On top of that, a particular observation was the very good outcome of patients treated with DCVax®-L at time of relapse plus TTF (1). The mode of action of TTF relies at least in part on an ICD immunotherapy effect (24). This finding illustrates the potential of multimodal immunotherapy, and offers perspectives for smart combination therapies for GBM patients in consecutive phases, which we have developed (25).

:)