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Summary

  • Interim results are for 19 patients who received two weeks of treatment; the protocol calls for 8 months of treatment.
  • Early results indicate that 11 patients have shown tumor necrosis and an immunological effect on the tumor.
  • Six patients have shown tumor shrinkage or stable disease, with one patient showing tumor shrinkage of 28%, just short of 30% which qualifies as a partial response.
  • The key is whether these early responses translate into complete or partial responses as patients progress through the next 7 1/2 months of treatment.

Introduction

Northwest Biotherapeutics (NASDAQ:NWBO) held a conference call on May 27th to discuss interim results of its Phase I/II, first-in-human trial of DCVax-Direct. This is a new type of dendritic cell vaccine in which the dendritic cells are injected directly into the tumor mass and pick up cancer antigens that are present in that specific tumor. This differs from its lead product, DCVax-L, in which tumor antigens are loaded into dendritic cells ex vivo and then reinjected into the body. This is an interesting new concept because of the means of administration, and because this is a more advanced dendritic cell that in animal studies has been shown to be several times more powerful in loading tumor antigens. This is dendritic cell cancer vaccine 2.0.

In this note, I summarize what I found to be key takeaway points in the conference call. I start with CEO Linda Powers' opening remarks. After that, she addressed questions that had been submitted before the meeting by participants. I found this to be a more informative way of conducting the call than the conventional method of letting analysts ask questions. This usually results in long-winded grandstanding by analysts.

Opening Remarks by Linda Powers

Ms. Powers stated that this Phase I/II trial involves both new technology platform and a new disease target. The Company's first product, DCVax-L, is targeted at glioblastoma multiforme initially, but has also been in preliminary trials in ovarian cancer and prostate cancer. In the case of glioblastoma multiforme, it is being studied as part of standard of care which is given shortly after surgical resection. Patients have not previously received chemotherapy or radiation.

Ms. Powers emphasized that the results are very early, and more time is needed to evaluate the ultimate effect of DCVax-Direct, but that the Company and investigators from MD Anderson are very encouraged. MD Anderson, which is conducting this trial, is one of the top two or three cancer centers in the US and very highly regarded.

In the treatment of most solid tumors, the first treatment is surgical resection of the tumor to remove as much of the primary tumor mass as possible. This is then followed by chemotherapy and radiation to further reduce the size of the tumor and its metastases. This trial is being conducted in patients with inoperable tumors, due either to the location of the tumor or because the tumor has metastasized to the extent that surgery would not be of benefit.

The patient group in which DCVax-Direct is being tested has very advanced disease. These patients have exhausted treatment options, often having gone through several prior courses of therapy. Most have the option of palliative therapy or an experimental drug like DCVax-Direct. Because the tumors have not been surgically resected, they are large tumors with metastases that are growing rapidly. These are very-difficult-to-treat patients in whom any kind of response is of great interest; this represents an urgent and unmet medical need. If DCVax-Direct is ultimately approved, its primary use will be in less severely ill, surgically resected patients who would be expected to respond better.

Ms. Powers said that over 58% of the first 19 patients in the trial who have received at least three injections over a 2-week period are showing responses to the drug. As a reminder, the trial protocol calls for six treatments given at day 0, day 7, day 14, and week 8, week 16, and week 32. These patients showing responses are only two weeks into an 8-month course of therapy

She compared this to the checkpoint inhibitor, nivolumab, of Bristol-Myers Squibb (NYSE:BMY). Nivolumab was used as a single agent in 94 heavily pre-treated melanoma patients. Of these patients, 28% had a complete or partial response. In 76 non-small cell lung cancer patients, 18% had complete or partial responses. Many of these responses were durable, lasting up to a year.

She emphasized that we can't directly compare results of DCVax-L with nivolumab. We don't know if the initial responses, which are based on the detection of significant tumor necrosis and immune cell infiltration into the tumor, with some cases of tumor shrinkage, will translate into durable complete or partial responses. So far, the best response seen in any patient is a 28% shrinkage of the tumor, which falls just short of the 30% shrinkage which qualifies as a partial response. On the other hand, the responses seen with DCVax-Direct are based on just two weeks of therapy. In immune therapy, responses usually improve over time, but this remains to be determined.

If DCVax-Direct can show 20% to 30% objective responses, it has to be viewed as an extremely significant drug. Wall Street analysts are super excited about the potential of nivolumab and Merck's (NYSE:MRK) similar drug lambrolizumab, with sales estimates of as much as $5 billion for these two drugs by 2020. This means that investors will be closely watching updates on the status of patients in the DCVax-Direct trial as the year progresses. Investors will want to see some objectives responses develop that are durable.

The DCVax-Direct trial is composed of a Phase I trial that will enroll 36 patients. In this conference call, Ms. Powers reported on the first 19 patients treated in the Phase I segment. After completion, the trial will roll seamlessly into a Phase II trial of 24 patients. This is an unusually large for a first-in-human trial. Ordinarily, such trials involve 12 to 18 patients.

The main focus of the Phase I portion of the trial is on safety, but indications of efficacy can also be seen. In terms of safety, the drug is extremely well-tolerated. The main side effect being seen is a fever at the time of injection that lasts for a day or two. This is a result of the biological effect of the drug, which causes an immune response. This can be treated with Tylenol. There has been one case of mild nausea reported, but investigators believe that this was caused by another drug being taken by the patient. There is pain upon injection of the needle that is comparable to that of a biopsy that can be treated with a local anesthetic. Relative to chemotherapy, the side effect profile is benign; this is an extremely important aspect of the drug.

Physicians involved in the trial report that DCVax-Direct is easy to administer using an imaging technology, such as ultrasound or CT, to direct the needle to the tumor in which it is to be injected. They believe that DCVax-Direct can be easily incorporated into their treatment regimens.

Early Results

The early results, as reported by NWBO on the 11 of 19 patients treated that showed an early response, were as follows:

  • 8 of 11 patients have shown signs of tumor necrosis (cell death), immune cell infiltration into the tumor and stable disease. Biopsies showed substantial or extensive tumor necrosis, as well as substantial accumulation of immune cells in and around the tumors.
  • 6 of these 8 patients showed tumor shrinkage or no disease progression, based on imaging studies.
  • The other 2 of 8 patients showed enlargement of their tumor, but the tumors based on biopsies had substantial necrosis and substantial infiltration of immune cells.
  • In addition to these 8 patients, there were 3 other patients that showed stable disease, but with no evidence of tumor necrosis or infiltration of immune cells.

In judging these results, she pointed out that we have to take into account that the results are early, as none of the patients have completed therapy that calls for six injections over 32 weeks or 8 months. The data indicates a meaningful initial effect on 11 of those 19 patients who have received at least three injections over a two-week period. She stated that what will be extremely important is whether these effects are temporary or whether they will hold or improve over time. Generally, immune therapies produce results more slowly, with an improving response over time, so she said she would hope there would be improvement with time, but this remains to be seen.

The question and answer part of the conference call produced some very meaningful insights into the data. A reproduction of these, along with my opinions can be found on my website as free content.

Investment Opinion

I continue with my buy on the stock.

Source: Northwest Biotherapeutics: Management Discusses Interim Data On Phase I/II Trial Of DCVax-Direct