A company called Advaxis is planning to test a new form of prostate cancer immunotherapy (ADXS-PSA) in combination with an investigational drug called pembrolizumab (an anti-PD-1 immune checkpoint inhibitor) in men with previously treated, metastatic, castration-resistant prostate cancer (mCRPC).
The full media release announcing this study (released this morning) can be found on the Advaxis corporate web site, and there is already another commentary about this study on the Reuters web site. The trial will be a Phase I/II trial and won’t be starting until early 2015. To date there is no information about the trial on the ClinicalTrials.gov web site, but we will try to make sure we know when such data are available.
This study is interesting because it is the first study that we are aware that has been designed to test the potential of an anti-PD-1 immune checkpoint inhibitor (commonly just called a PD-1 inhibitor) in the treatment of advanced prostate cancer. However, PD-1 inhibition has been very successful in extending the survival of patients with advanced forms of melanoma (an aggressive form of skin cancer that has long been know to be responsive to immunotherapeutic interventions).
PD-1 inhibitors work by blocking the effects of a protein called PD-1 (formally known as the programmed cell death 1 protein), which normally controls the growth and release of immune system cells, thus making it easier for immune system cells to attack invading cancer cells. ADXS-PSA — the immunotherapeutic agent developed by Advaxis — is a modified Listeria bacterium fused to the PSA protein normally released into the blood stream by prostate cancer cells. ADXS-PSA has been designed to stimulate the creation and release of T-cells that are primed to recognize and kill prostate cancer cells. Thus, it is hoped that, by combining two forms of agent that work on the immune system, it may be possible to significantly increase the impact of either drug alone in the management of late stage prostate cancer.
Like ADXS-PSA, the PD-1 inhibitor being used in the current study, pembrolizumab (also known as MK-3475), is still investigational, but the developer, Merck, released some impressive data on the effects of this drug in the treatment of melanoma at the annual meeting of the American Society for Clinical Oncology (ASCO) earlier this year, and it is expected that this drug will be approved by the FDA for the treatment of patients with metastatic melanoma at some point in the reasonably near future.
Whether this combination of a PD-1 inhibitor with another form of immunotherapy will really have significant effects in the treatment of late stage prostate cancer is, of course, utterly unknown at this time. However, for men with mCRPC who are still in reasonable health but have already shown signs of progression on a drug like abiraterone acetate or enzalutamide, this might well be a whole new area of opportunity.
Filed under: Drugs in development, Living with Prostate Cancer, Management, Treatment | Tagged: ADXS-PSA, castration-resistant, immunotherapy, mCRPC, metastatic, PD-1, pembrolizumab |
THE "NEW" PROSTATE CANCER INFOLINK 
There is a clinical trial (NCT01420965) of anti-PD-1 together with Provenge and low dose cyclophosphamide at Georgia Regents University in Augusta. I’m very hopeful about such immune cocktails, but there are significant risks too. Close monitoring is essential.
Allen:
Hmmm … This trial (which I had admittedly never heard of) was started in 2011 or at worst 2012 and still hasn’t managed to enroll 57 patients?! On top of which, Teva pulled the plug in January 2013 on its development relationship with CureTech for Curetech’s CT-011 anti-PD-1 agent! And Dendreon is losing money hand over fist.
Something tells me that this isn’t a trial I would have high hopes for. And that’s before you persuade me to take cyclophosphamide along with the two immunotherapeutics!
I just called them. They are continuing recruitment. They completed Phase I, which is antibody response to Provenge, and are just starting on Phase II randomization to the other treatments. They are about to expand to two more sites in Knoxville, TN, and Athens, GA, and are trying to find other sites as well. They say that they have supplies of all medications necessary. After 5 weeks of treatment, they have patients come in every 6 weeks for monitoring.
Well, they can’t possibly have “supplies” of all the sipuleucel-T because each batch has to be individually manufactured for each patient. However, we’ll just have to be patient and see what happens.
Just a quick note that Merck’s PD-1 inhibitor, pembrolizumab (Keytruda) — mentioned above, was approved by the FDA on Thursday, September 4, for the treatment of advanced melanoma patients who don’t respond to other drugs. This is the first PD-1 inhibitor to gain approval anywhere in the world. Note also that the expected cost for a course of therapy will be of the order of US$12,000 a month.
For people tracking this topic, it may help to cross-reference pembrolizumab’s trade name (Keytruda®) and former names (lambrolizumab and MK-3475).
As of January 2015, I see one clinical trial completed, one now recruiting, and one more recruiting soon:
— NCT00441337: pembrolizumab (Phase I, completed; no study results posted yet
— NCT02312557: pembrolizumab (Phase II, now recruiting patients with mCRPC after enzalutamide = Xtandi®)
— NCT02325557: ADXS31-142 alone, ADXS31-142 + pembrolizumab (Phase I/II, not yet open)
Other anti-PD1/anti-PDL1 agents are also receiving consideration in clinical trials, such as CT-011 (NCT01420965) and
MSB0010718C (NCT01772004).