Biotechnology company Northwest Biotherapeutics is planning to begin phase I/II DCVax-Direct clinical trial for all inoperable solid tumour cancers within approximately the next sixty days.

As a phase I/II trial, this trial is not blinded and the results will be seen as the trial proceeds. With an efficacy endpoint of tumour regression (i.e., tumour shrinkage or elimination), this innovative trial is expected to yield meaningful ongoing results by the second half of 2013.

This clinical trial is approved by the FDA for all types of solid tumour cancers (i.e., cancers in any tissues of the body), and is configured to provide rapid results. In the phase I portion, it will test both safety and a variety of dosing regimes, and will do so in multiple different cancers – avoiding the need to conduct separate phase I studies in each such cancer, as is usually the case. Then, the trial will go directly into the phase II portion, testing for efficacy, without the need for another FDA review.

The endpoint for measuring efficacy in the phase II portion of the trial will be tumor regression. This endpoint is a particularly important one clinically: once tumors are established, if they cannot be surgically removed, it is very difficult to stop their growth and their spread. This endpoint is also important from a regulatory standpoint: it is the endpoint used most frequently for FDA-granted accelerated approval. Further, this endpoint is a rapid one: typically, if tumour regression is going to occur, it is anticipated to be seen within a few months after treatment – far sooner than other clinical trial endpoints such as progression free survival (PFS) or overall survival (OS).

In multiple pre-clinical studies of various cancers in animals, direct injection of DCVax-Direct into some of the tumors in each animal resulted in complete clearance of all tumours in 80 per cent to 100 per cent of all of the animals in the various studies – both the tumours that were injected and the tumours that were not injected, indicating a systemic immune response. Further, the tumours were cleared relatively rapidly: within weeks after the DCVax-Direct injections. Equally as important, sixty days after the tumors were cleared from the animals in these preclinical studies, the animals were re-injected with the same tumor cells that readily established tumours at the outset of the studies. This time, tumours failed to establish, indicating immune memory.

The key to this novel approach for potentially fatal inoperable tumors was the NW Bio discovery that partial activation of dendritic cells, in a certain way and to a certain degree, produces dendritic cells that are able to perform both of the two key steps needed to mobilize an overall immune response attacking the cancer. Neither immature dendritic cells nor fully mature dendritic cells are able to do this.

"Inoperable tumours represent a severe and widespread unmet medical need,” commented Linda F Powers, CEO of NW Bio.  “Some types of cancer are inoperable even as to the primary tumours, and many others are inoperable due to the spread of metastases. DCVax-Direct can potentially offer an important new treatment option, which can address many or most of these situations. It is very exciting to contemplate the potential for seeing rapid results in our DCVax-Direct trial later this year, while we continue in parallel to execute our lead programme: our international phase III trial with DCVax-L for brain cancer.”

Northwest Biotherapeutics is focused on developing immunotherapy products to treat cancers more effectively than current treatments, without toxicities of the kind associated with chemotherapies, and on a cost-effective basis, in both the United States and Europe.