Full Press Release Details
PRIMA BIOMED MANAGEMENT PRESENTS CVACTM PHASE 2 TRIAL RESULTS -
Prima BioMed (ASX: PRR; NASDAQ: PBMD; ISIN: US74154B2034)
2nd October 2013 8:00am AEST
James Moses: Investor Relations Representative
morning ladies and gentlemen and welcome to Prima BioMed s presentation of the CAN-003 clinical trial analysis. My name is James Moses, Prima s Investor Relations Representative. With me today is Mr Matthew Lehman, the company s Chief
Executive Officer, and Dr Sharron Gargosky, Prima s Chief Technical Officer.
Before we begin, I d like to remind you that during this call, we
will make forward looking statements that are subject to risks and uncertainties that may cause actual results to differ from the results discussed in the forward looking statements. Reference to these risks and uncertainties are disclosed in detail
in our public announcements to the ASX and our disclosure filings with the US Securities and Exchange Commission. The CAN-003 protocol is a phase 2 clinical trial of CVac for the treatment of epithelial ovarian cancer patients in remission after
successful first or second line therapy.
As you d be aware, the company announced top line analysis of this trial on September 18 and Dr
Jeffery Goh, one of the study s lead investigators, presented the data analysis yesterday at the European Cancer Congress. For those interested, a copy of Dr Goh s presentation will be available via Prima BioMed s website.
Onto our call this morning, and during the call, Dr Gargosky will first present an analysis of the CAN-003 trial and then Mr Lehman will present some of the
implications of the data and the forward looking development plans for CVac.
I ll now turn the call over to Dr Sharron Gargosky.
Sharron Gargosky: Chief Technical Officer
James. Well hello everyone and thank you for joining us today. As James just mentioned, Dr Goh gave an excellent presentation on this CAN-003 analysis just yesterday in Amsterdam at the European Cancer Congress and I m really pleased to
report that Dr Goh s presentation was very well attended and well received by the leaders in the ovarian cancer space. However, as Dr Goh is currently on a flight back to Australia, I have the pleasure of delivering this summary update to
the shareholders on behalf of Dr Goh and the CAN-003 study team.
So I d like to start with reviewing the key study entry criteria and the
design of the study, which is on slide 3. So 63 women were enrolled on the CAN-003 study after having achieved complete remission from first or second line treatment. Prior to joining the trial, all women underwent cytoreductive - or debulking
- surgery to remove as much cancer as possible and completed the conventional chemotherapy. These patients were then allowed to enrol within twelve weeks of having achieved complete remission. Now, the first seven patients were not randomised and
they received CVac. This was part of the trial and was intended to assess the manufacturing comparability between Australia and the United States manufacturing sites, which was successfully achieved.
After the first seven patients, 56 were then randomised to either receive CVac or to the standard of care, or control, group. The CVac group received ten
doses of CVac over a 56 week period and each dose of CVac contains about 60 million dendritic cells that have been primed or treated with the mucin 1 antigen. The control group didn t receive any active treatment and was basically an
observational control group. Observation, as many of you know, is the current standard of care for most women in remission with ovarian cancer.
total, 43 patients who joined the study were in first remission and 20 were in second remission.
The CVac dosing started within ten weeks of enrolment
into the trial and the trial specified monitoring patients until the disease progressed or for two years. So this progression was defined individually by each investigator based on their patients CA-125 values and radiological evaluations.
Progression-free survival is defined as each patient s time interval between the time they were randomised and entered the study to the date that the disease progressed or death.
The two primary clinical objectives of this trial were to assess the safety profile of CVac and to assess
CVac s impact on progression-free survival. The secondary clinical objectives of the trial were to assess CVac s impact on overall survival of the patients and to evaluate the immunological or immune responses to the CVac treatment.
Now when we look at safety evaluations in these trials, we use the data of all 63 patients, and that s referred to as the safety population .
But when we look at efficacy end points, we use the intent-to-treat population, or sometimes referred to as the ITT population . The ITT population includes all 56 patients who were randomised regardless of how long they stayed on
the trial, but does exclude the seven non-randomised patients.
Now in terms of statistical powering and plans for the CAN-003 trial, this trial was not
necessarily powered to detect a statistically significant difference in the progression-free survival. As is very common in phase 2 trials, however, the sample size was considered adequate on clinical grounds to assess the rates of disease
progression, trends in immunological outcome, and potential disease markers and other clinical outcomes. And the purpose of such data is then to assist with the planning of the future studies.
If we move onto slide 4, in summary we were able to make the following conclusions from the CAN-003 trial data to date. On the safety objective, CVac was well
tolerated and non-toxic. In terms of immune activity, CVac induced a Mucin-1 specific T-cell response and CVac did not induce an antibody response. On the progression-free survival or PFS objective, there were
no statistical significant differences observed in PFS. We did, however, observe divergent trends between first and second line remission groups. And regarding the overall survival, eight patients have been confirmed to decease to date and
we ll continue to monitor the overall survival signals in the trial.
I d like to now go on and discuss a little bit more of each objective in
detail. If we move onto slide 6, we ll start discussing the serious adverse events. There were ten adverse events in the past three years or more. Nine of these were definitely not related to study treatment and one SAE was
considered to be unlikely related to the study treatment. One serious adverse event, SAE, resulted in death, but that SAE was
considered definitely not related to the study agent treatment. When looking at AEs on slide 7, or adverse events, the most common adverse events were defined as related to the
CVac treatment, but included symptoms at the injection site such as localised pain, erythema, redness, swelling, burning and some broader symptoms of fatigue, lethargy and dizziness, but the majority of such events were mild and resolved within one
day. There were few severe adverse events that we saw and only one that lasted longer than a day and that was a bunion considered unlikely related to CVac. Two severe events were classified as probably related or
possibly related to CVac and those were widespread itch and headache. So, in general, from the CAN-003 data, we can conclude that CVac therapy is well tolerated and non-toxic.
Moving onto the immune monitoring analysis on slide 8. First, we looked at mucin 1 antibody responses in patients. Now, with cell-based therapies like CVac,
we do not expect to see any antibodies developing in patients against mucin 1. And we were very pleased to see that when we measured this, we saw very low or undetectable levels of antibody. So these antibodies were not generated against the CVac
treatment. Only a couple of patients showed detectable antibodies to mucin 1 and those patients were actually in the observational control group and not actually part of the CVac group. So we wanted to see with therapies like CVac what the potent
T cell response would be, especially with respect to the CD8 and CD4 T cells.
And in slide 9 we have a summary of each patient s best immune
response to the CVac treatment. And you can see that CVac induces a broad activity in the T cells. Most specifically, this chart summarises the T cell responses in CVac patients in either first or second complete remission. This is noted as CR-1,
for complete remission 1, and CR-2, for complete remission 2.
We also looked at these patients combined as a group and that represents the CR-1 plus
CR-2 line in this chart. It is then summarised that in here the statistical significance of the activity of each cytokine for each T cell type. One star represents a statistical significance at a p-value of less than 0.1 and two stars indicate a
statistically significant response at a p-value of .05.
Additional work is ongoing at Prima to further investigate this immune response, but we re
very pleased to see this really strong good type of immunological activity with the important T cell types of CD4 and CD8 and their respective cytokine expression. And we believe that this type of T cell activity can yield positive clinical outcomes
The next point we review is progression-free survival on slide 10. Now, what you can see here is the so-called
Kaplan-Meier Estimate of progression-free survival for those 56 patients who were randomised in the ITT population. This graph estimates the percentage of patients who had not yet progressed at the continuous points in time. For example, you see
that at about six months after randomisation, there s a slightly higher percentage of CVac patients - that is the blue line - that had not progressed compared to the observational arm. You also see a separation around the twelve month mark
where again the blue line is a little above the observational line. But, however, when you look at the overall graph we did not observe a trend that indicates a difference in the progression-free survival between CVac and observational standard of
When you look at the same Kaplan-Meier estimates separately for the patients in first and second line remission, you ll see in slide 11
that there is a trend that would indicate that the observational group did better than the CVac group in first remission. And in second remission, the trend would indicate that the CVac patients did better than the observational group. However, we
would caution that these are relatively small numbers of patients and that neither of these trends are considered statistically significant.
moving on to the overall survival data in slide 12. As of mid-September, five patients had withdrawn their consent to participate in the CAN-003 study. We re monitoring the 58 remaining patients for longer term to collect their overall survival
data. And currently, in the CVac group, four patients have deceased and 28 are confirmed alive. In the observational group, four patients have deceased and 20 are confirmed alive. There are two patients whose status has not been confirmed as of
September, but we will continue to observe these patients and collect overall survival data.
With that now, I would like to turn the presentation over to
Matt and he can review some of the conclusions and implications of our CAN-003 data analysis. Thanks Matt.
Matthew Lehman: Chief Executive Officer
Well, thank you Sharron, and thanks for that nice overview. So as we look here at slide 13 on the slide deck that was presented previously, we ll
start here with some important conclusions that we can draw from the CAN-003 protocol analysis.
First, we are very pleased to have demonstrated the
ability to transfer manufacturing technology and produce a comparable product in multiple manufacturing facilities. We do strongly believe that this capability is quite unique to Prima and it is important for the future commercial success of
Second, we are also very pleased to confirm that CVac is well tolerated and that it does induce the right type of cellular immune
response in patients. This indicates to us that we have a promising product as we continue in development.
Similar to recent findings with a number of
other cancer immunotherapies, we are not seeing a clinically meaningful trend on the progression-free survival endpoint. Our hypothesis, and the reason for choosing PFS as an endpoint in our CVac clinical trials, was because ovarian cancer patients
do have a somewhat longer period in remission than a number of other cancer types - for example metastatic prostate or metastatic melanoma. So we believed, or our hypothesis was, that there would be enough time for a full course of 56 weeks of CVac
dosing to have an observable effect on the PFS endpoint. But based on the data we have, and looking at data from other trials in cancer immune therapy that have reported since CAN-003 started three years ago in 2010, it certainly does not appear to
be the case that CVac will have an important or clinically significant effect on PFS.
There is a lot of interesting scientific debate about why cancer
immunotherapies may not have much impact on the time to progression or time to recurrence or progression-free survival. They re all similar measures of endpoints on these clinical trials. Paraphrasing, and I ll paraphrase here, and this is
a recent article, it is in the July 2013 issue of Nature Reviews Drug Discovery. So, it says in there, Drug developers have learned the hard way during the development of immunotherapies that it takes time to prime T cells to
attack. Immunotherapies, as a result, take longer to induce an effect than do cytotoxic and targeted agents. Moreover, if new tumours developed during this lifetime, a patient will be classified as a progressor under traditional trial guidelines
even if she later has a complete and durable response. Such failures undermine the ability of trials to demonstrate efficacy.
Again, continuing on from this article, Investigators are moving towards adopting more flexible
immune-related response criteria that may account for these responders. But according to Gary Gilliland, Merck s Oncology Franchise Head, when it comes to regulatory approval, the old RECIST - the response evaluation criteria in solid tumours -
these RECIST criteria remain the accepted benchmark.
Dr Gilliland is quoted as saying, and we at Prima also agree, that we need to obtain better
alignment with regulators around which of those criteria are most appropriate.
I do very much encourage our listeners here to our presentation today to
read more about the practical issues involving trial design of cancer immunotherapies. There are really a number of good resources on the web. We here at Prima, we will also be updating our website and we ll be including a section for more
background research to be able to research cancer immunotherapy.
Certainly, it will be very important for us to continue observation of clinical signals
based on overall survival data. We will continue with immune monitoring work on our upcoming CVac trials and there have been some very interesting new technologies developed even in the past couple of years that may give us even better immune